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Статті в журналах з теми "DOTA/NOTA"

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Автор: Grafiati

Опубліковано: 7 липня 2024

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1

Haeger, Arlette, Cristian Soza-Ried, Vasko Kramer, Ana Hurtado de Mendoza, Elisabeth Eppard, Noémie Emmanuel, Johanna Wettlin, Horacio Amaral, and René Fernández. "Al[18F]F-NOTA-Octreotide Is Comparable to [68Ga]Ga-DOTA-TATE for PET/CT Imaging of Neuroendocrine Tumours in the Latin-American Population." Cancers 15, no. 2 (January 10, 2023): 439. http://dx.doi.org/10.3390/cancers15020439.

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PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE.

2

Dam, Johan Hygum, Niels Langkjær, Christina Baun, Birgitte Brinkmann Olsen, Aaraby Yoheswaran Nielsen, and Helge Thisgaard. "Preparation and Evaluation of [18F]AlF-NOTA-NOC for PET Imaging of Neuroendocrine Tumors: Comparison to [68Ga]Ga-DOTA/NOTA-NOC." Molecules 27, no. 20 (October 12, 2022): 6818. http://dx.doi.org/10.3390/molecules27206818.

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Background: The somatostatin receptors 1–5 are overexpressed on neuroendocrine neoplasms and, as such, represent a favorable target for molecular imaging. This study investigates the potential of [18F]AlF-NOTA-[1-Nal3]-Octreotide and compares it in vivo to DOTA- and NOTA-[1-Nal3]-Octreotide radiolabeled with gallium-68. Methods: DOTA- and NOTA-NOC were radiolabeled with gallium-68 and NOTA-NOC with [18F]AlF. Biodistributions of the three radioligands were evaluated in AR42J xenografted mice at 1 h p.i and for [18F]AlF at 3 h p.i. Preclinical PET/CT was applied to confirm the general uptake pattern. Results: Gallium-68 was incorporated into DOTA- and NOTA-NOC in yields and radiochemical purities greater than 96.5%. NOTA-NOC was radiolabeled with [18F]AlF in yields of 38 ± 8% and radiochemical purity above 99% after purification. The biodistribution in tumor-bearing mice showed a high uptake in tumors of 26.4 ± 10.8 %ID/g for [68Ga]Ga-DOTA-NOC and 25.7 ± 5.8 %ID/g for [68Ga]Ga-NOTA-NOC. Additionally, [18F]AlF-NOTA-NOC exhibited a tumor uptake of 37.3 ± 10.5 %ID/g for [18F]AlF-NOTA-NOC, which further increased to 42.1 ± 5.3 %ID/g at 3 h p.i. Conclusions: The high tumor uptake of all radioligands was observed. However, [18F]AlF-NOTA-NOC surpassed the other clinically well-established radiotracers in vivo, especially at 3 h p.i. The tumor-to-blood and -liver ratios increased significantly over three hours for [18F]AlF-NOTA-NOC, making it possible to detect liver metastases. Therefore, [18F]AlF demonstrates promise as a surrogate pseudo-radiometal to gallium-68.

3

Lee, Inki, Min Hwan Kim, Kyongkyu Lee, Keumrok Oh, Hyunwoo Lim, Jae Hun Ahn, Yong Jin Lee, Gi Jeong Cheon, Dae Yoon Chi, and Sang Moo Lim. "Comparison of the Effects of DOTA and NOTA Chelators on 64Cu-Cudotadipep and 64Cu-Cunotadipep for Prostate Cancer." Diagnostics 13, no. 16 (August 11, 2023): 2649. http://dx.doi.org/10.3390/diagnostics13162649.

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Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep and 64Cu-cunotadipep, on pharmacokinetics. Methods: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed tomography (CT) and biodistribution analysis were performed using PSMA+ PC3-PIP and PSMA− PC3-flu tumor xenografts. Results: The serum stability of DOTA- or NOTA-conjugated 64Cu-cudotadipep and 64Cu-cunotadipep was >97%. The Ki value of the NOTA derivative, cunotadipep, in the in vitro affinity binding analysis was higher (2.17 ± 0.25 nM) than that of the DOTA derivative, cudotadipep (6.75 ± 0.42 nM). The cunotadipep exhibited a higher cellular uptake (6.02 ± 0.05%/1 × 106 cells) compared with the cudotadipep (2.93 ± 0.06%/1 × 106 cells). In the biodistribution analysis and microPET/CT imaging, the 64Cu-labeled NOTA derivative, 64Cu-cunotadipep, demonstrated a greater tumor uptake and lower liver uptake than the DOTA derivative. Conclusions: This study indicates that the PSMA-targeted 64Cu-cunotadipep can be applied in clinical practice owing to its high diagnostic power for prostate cancer.

4

Kis, Adrienn, Judit P. Szabó, Noémi Dénes, Adrienn Vágner, Gábor Nagy, Ildikó Garai, Anikó Fekete, et al. "In Vivo Imaging of Hypoxia and Neoangiogenesis in Experimental Syngeneic Hepatocellular Carcinoma Tumor Model Using Positron Emission Tomography." BioMed Research International 2020 (August 7, 2020): 1–10. http://dx.doi.org/10.1155/2020/4952372.

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Introduction. Hypoxia-induced ανβ3 integrin and aminopeptidase N (APN/CD13) receptor expression play an important role in tumor neoangiogenesis. APN/CD13-specific 68Ga-NOTA-c(NGR), ανβ3 integrin-specific 68Ga-NODAGA-[c(RGD)]2, and hypoxia-specific 68Ga-DOTA-nitroimidazole enable the in vivo detection of the neoangiogenic process and the hypoxic regions in the tumor mass using positron emission tomography (PET) imaging. The aim of this study was to evaluate whether 68Ga-NOTA-c(NGR) and 68Ga-DOTA-nitroimidazole allow the in vivo noninvasive detection of the temporal changes of APN/CD13 expression and hypoxia in experimental He/De tumors using positron emission tomography. Materials and Methods. 5×106 hepatocellular carcinoma (He/De) cells were used for the induction of a subcutaneous tumor model in Fischer-344 rats. He/De tumor-bearing animals were anaesthetized, and 90 min after intravenous injection of 10.2±1.1 MBq 68Ga-NOTA-c(NGR) or 68Ga-NODAGA-[c(RGD)]2 (as angiogenesis tracers) or 68Ga-DOTA-nitroimidazole (for hypoxia imaging), whole-body PET/MRI scans were performed. Results. Hypoxic regions and angiogenic markers (αvβ3 integrin and APN/CD13) were determined using 68Ga-NOTA-c(NGR), 68Ga-DOTA-nitroimidazole, and 68Ga-NODAGA-[c(RGD)]2 in subcutaneously growing He/De tumors in rats. 68Ga-NOTA-c(NGR) showed the strong APN/CD13 positivity of He/De tumors in vivo, by which observation was confirmed by western blot analysis. By the qualitative analysis of PET images, heterogenous accumulation was found inside He/De tumors using all radiotracers. Significantly (p≤0.01) higher SUVmean and SUVmax values were found in the radiotracer avid regions of the tumors than those of the nonavid areas using hypoxia and angiogenesis-specific radiopharmaceuticals. Furthermore, a strong correlation was found between the presence of angiogenic markers, the appearance of hypoxic regions, and the tumor volume using noninvasive in vivo PET imaging. Conclusion. 68Ga-DOTA-nitroimidazole and 68Ga-NOTA-c(NGR) are suitable diagnostic radiotracers for the detection of the temporal changes of hypoxic areas and neoangiogenic molecule (CD13) expression, which vary during tumor growth in a hepatocellular carcinoma model.

5

Drahoš, Bohuslav, Vojtěch Kubíček, Célia S. Bonnet, Petr Hermann, Ivan Lukeš, and Éva Tóth. "Dissociation kinetics of Mn2+ complexes of NOTA and DOTA." Dalton Transactions 40, no. 9 (2011): 1945. http://dx.doi.org/10.1039/c0dt01328e.

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6

Poulie, Christian B. M., Jesper T. Jørgensen, Vladimir Shalgunov, Georgios Kougioumtzoglou, Troels Elmer Jeppesen, Andreas Kjaer, and Matthias M. Herth. "Evaluation of [64Cu]Cu-NOTA-PEG7-H-Tz for Pretargeted Imaging in LS174T Xenografts—Comparison to [111In]In-DOTA-PEG11-BisPy-Tz." Molecules 26, no. 3 (January 21, 2021): 544. http://dx.doi.org/10.3390/molecules26030544.

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Pretargeted nuclear imaging for the diagnosis of various cancers is an emerging and fast developing field. The tetrazine ligation is currently considered the most promising reaction in this respect. Monoclonal antibodies are often the preferred choice as pretargeting vector due to their outstanding targeting properties. In this work, we evaluated the performance of [64Cu]Cu-NOTA-PEG7-H-Tz using a setup we previously used for [111In]In-DOTA-PEG11-BisPy-Tz, thereby allowing for comparison of the performance of these two promising pretargeting imaging agents. The evaluation included a comparison of the physicochemical properties of the compounds and their performance in an ex vivo blocking assay. Finally, [64Cu]Cu-NOTA-PEG7-H-Tz was evaluated in a pretargeted imaging study and compared to [111In]In-DOTA-PEG11-BisPy-Tz. Despite minor differences, this study indicated that both evaluated tetrazines are equally suited for pretargeted imaging.

7

Jussing, Emma, Stefan Milton, Erik Samén, Mohammad Mahdi Moein, Lovisa Bylund, Rimma Axelsson, Jonathan Siikanen, and Thuy A. Tran. "Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers." Biomolecules 11, no. 8 (July 29, 2021): 1118. http://dx.doi.org/10.3390/biom11081118.

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By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.

8

Milton, Stefan, Emma Jussing, Klas Bratteby, Mélodie Ferrat, Erik Samen, Thuy Tran, and Jonathan Siikanen. "First time evaluation of 45Ti for radiolabeling of NOTA and DOTA chelators." Nuclear Medicine and Biology 126-127 (November 2023): 108721. http://dx.doi.org/10.1016/j.nucmedbio.2023.108721.

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9

Ranyuk, Elena, Réjean Lebel, Yves Bérubé-Lauzière, Klaus Klarskov, Roger Lecomte, Johan E. van Lier, and Brigitte Guérin. "68Ga/DOTA- and 64Cu/NOTA-Phthalocyanine Conjugates as Fluorescent/PET Bimodal Imaging Probes." Bioconjugate Chemistry 24, no. 9 (August 26, 2013): 1624–33. http://dx.doi.org/10.1021/bc400257u.

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10

Alex Brown, M., Thomas Brossard, and David A. Rotsch. "Examination of lutetium(III)-DOTA and copper(II)-NOTA solution structures using EXAFS." Inorganica Chimica Acta 482 (October 2018): 118–21. http://dx.doi.org/10.1016/j.ica.2018.05.031.

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11

Hrynchak, Ivanna, Diana Cocioabă, Alexandra I. Fonseca, Radu Leonte, Sérgio J. C. do Carmo, Roxana Cornoiu, Amílcar Falcão, Dana Niculae, and Antero J. Abrunhosa. "Antibody and Nanobody Radiolabeling with Copper-64: Solid vs. Liquid Target Approach." Molecules 28, no. 12 (June 9, 2023): 4670. http://dx.doi.org/10.3390/molecules28124670.

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Antibody and nanobody-based copper-64 radiopharmaceuticals are increasingly being proposed as theranostic tools in multiple human diseases. While the production of copper-64 using solid targets has been established for many years, its use is limited due to the complexity of solid target systems, which are available in only a few cyclotrons worldwide. In contrast, liquid targets, available in virtually in all cyclotrons, constitute a practical and reliable alternative. In this study, we discuss the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. Copper-64 production from solid targets was performed on a TR-19 cyclotron with an energy of 11.7 MeV, while liquid target production was obtained by bombarding a nickel-64 solution using an IBA Cyclone Kiube cyclotron with 16.9 MeV on target. Copper-64 was purified from both solid and liquid targets and used to radiolabel NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab conjugates. Stability studies were conducted on all radioimmunoconjugates in mouse serum, PBS, and DTPA. Irradiation of the solid target yielded 13.5 ± 0.5 GBq with a beam current of 25 ± 1.2 μA and an irradiation time of 6 h. On the other hand, irradiation of the liquid target resulted in 2.8 ± 1.3 GBq at the end of bombardment (EOB) with a beam current of 54.5 ± 7.8 μA and an irradiation time of 4.1 ± 1.3 h. Successful radiolabeling of NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab with copper-64 from both solid and liquid targets was achieved. Specific activities (SA) obtained with the solid target were 0.11, 0.19, and 0.33 MBq/μg for NODAGA-Nb, NOTA-Nb, and DOTA-trastuzumab, respectively. For the liquid target, the corresponding SA values were 0.15, 0.12, and 0.30 MBq/μg. Furthermore, all three radiopharmaceuticals demonstrated stability under the testing conditions. While solid targets have the potential to produce significantly higher activity in a single run, the liquid process offers advantages such as speed, ease of automation, and the feasibility of back-to-back production using a medical cyclotron. In this study, successful radiolabeling of antibodies and nanobodies was achieved using both solid and liquid targets approaches. The radiolabeled compounds exhibited high radiochemical purity and specific activity, rendering them suitable for subsequent in vivo pre-clinical imaging studies.

12

Luyten, Kaat, Tom Van Loy, Christopher Cawthorne, Christophe M. Deroose, Dominique Schols, Guy Bormans, and Frederik Cleeren. "D-Peptide-Based Probe for CXCR4-Targeted Molecular Imaging and Radionuclide Therapy." Pharmaceutics 13, no. 10 (October 5, 2021): 1619. http://dx.doi.org/10.3390/pharmaceutics13101619.

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Positron emission tomography (PET) imaging of the C-X-C chemokine receptor 4 (CXCR4) with [68Ga]PentixaFor has intrinsic diagnostic value and is used to select patients for personalized CXCR4-targeted radionuclide therapy with its therapeutic radiopharmaceutical companion [177Lu]PentixaTher. However, a CXCR4-targeting radiopharmaceutical labeled with fluorine-18 is still of high value due to its favorable characteristics over gallium-68. Furthermore, clinical results with [177Lu]PentixaTher are promising, but there is still room for improvement regarding pharmacokinetics and dosimetry profile. Therefore, this study aimed to develop innovative CXCR4-targeting radiopharmaceuticals, both for diagnostic and therapeutic purposes, starting from a D-amino acid-based peptide probe (DV1-k-(DV3)) that conserves high CXCR4 binding affinity after radiolabeling. AlF-NOTA-DV1-k-(DV3) showed similar in vitro binding affinity to human CXCR4 (hCXCR4) compared to [natGa]PentixaFor (half-maximal inhibitory concentration (IC50): 5.3 ± 0.9 nM and 8.6 ± 1.1 nM, respectively) and also binds to murine CXCR4 (mCXCR4) (IC50: 33.4 ± 13.5 nM) while [natGa]PentixaFor is selective for hCXCR4 (IC50 > 1000 nM for mCXCR4). Both the diagnostic radiotracers based on the DV1-k-(DV3) vector platform, [18F]AlF-NOTA-DV1-k-(DV3) and [68Ga]Ga-DOTA-DV1-k-(DV3), and their therapeutic companion [177Lu]Lu-DOTA-DV1-k-(DV3) were successfully produced in high yield, demonstrated high in vitro and in vivo stability, and have the same favorable pharmacokinetic profile. Furthermore, in wild-type mice and a hCXCR4-expressing tumor model, [18F]AlF-NOTA-DV1-k-(DV3) shows CXCR4-specific targeting in mCXCR4-expressing organs such as liver (mean standardized uptake value (SUVmean) 8.2 ± 1.0 at 75 min post-injection (p.i.)), spleen (SUVmean 2.5 ± 1.0 at 75 min p.i.), and bone (SUVmean 0.4 ± 0.1 at 75 min p.i., femur harboring bone marrow) that can be blocked with the CXCR4 antagonist AMD3100. However, in a hCXCR4-expressing tumor model, tumor uptake of [18F]AlF-NOTA-DV1-k-(DV3) was significantly lower (SUVmean 0.6 ± 0.2) compared to [68Ga]PentixaFor (SUVmean 2.9). This might be explained by the high affinity of [18F]AlF-NOTA-DV1-k-(DV3) toward both mCXCR4 and hCXCR4. High mCXCR4 expression in mouse liver results in a large fraction of [18F]AlF-NOTA-DV1-k-(DV3) that is sequestered to the liver, resulting despite its similar in vitro affinity for hCXCR4, in lower tumor accumulation compared to [68Ga]PentixaFor. As CXCR4 is not expressed in healthy human liver, the findings in mice are not predictive for the potential clinical performance of this novel class of CXCR4-targeting radiotracers. In conclusion, the DV1-k-(DV3) scaffold is a promising vector platform for translational CXCR4-directed research.

13

Rinne, Sara S., Charles Dahlsson Leitao, Zahra Saleh-nihad, Bogdan Mitran, Vladimir Tolmachev, Stefan Ståhl, John Löfblom, and Anna Orlova. "Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules." International Journal of Molecular Sciences 21, no. 6 (March 13, 2020): 1972. http://dx.doi.org/10.3390/ijms21061972.

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HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.

14

Gaillard, Michel, Hussein Kanso, Franck Denat, Carole Calas-Blanchard, Nicolas Inguimbert, and Thierry Noguer. "Fe(III)-DOTA/Fe(III)-NOTA Complexes: Attractive Alternative Markers for Future Electrochemical Biosensors." Journal of The Electrochemical Society 167, no. 11 (June 30, 2020): 117502. http://dx.doi.org/10.1149/1945-7111/ab9e80.

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15

Kiviniemi, Anu, Joonas Mäkelä, Jussi Mäkilä, Tiina Saanijoki, Heidi Liljenbäck, Päivi Poijärvi-Virta, Harri Lönnberg, Tiina Laitala-Leinonen, Anne Roivainen, and Pasi Virta. "Solid-Supported NOTA and DOTA Chelators Useful for the Synthesis of 3′-Radiometalated Oligonucleotides." Bioconjugate Chemistry 23, no. 9 (August 20, 2012): 1981–88. http://dx.doi.org/10.1021/bc300253t.

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16

Desbois, Nicolas, Sandrine Pacquelet, Adrien Dubois, Clément Michelin, and Claude P. Gros. "Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition." Beilstein Journal of Organic Chemistry 11 (November 17, 2015): 2202–8. http://dx.doi.org/10.3762/bjoc.11.239.

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The Cu(I)-catalysed Huisgen cycloaddition, known as “click” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI.

17

Crespo, Óscar Vara, Jorge Turmo Arnal, and Ángel Rodríguez García-Brazales. "Las raíces intelectuales de la economía evolutiva." Revista de Historia Económica / Journal of Iberian and Latin American Economic History 23, no. 1 (March 2005): 177–86. http://dx.doi.org/10.1017/s021261090001185x.

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La economía evolutiva ha experimentado en los últimos años un notable auge en el ámbito científico europeo, desarrollando una amplia panoplia de modelos y teorías destinadas a estudiar diversos aspectos de los procesos económicos. Aunque la economía evolutiva se caracteriza como tal por utilizar los modelos poblacionales de la biología evolutiva, adopta elementos cruciales de las obras de Schumpeter y Simon, lo que dota a su trabajo de una gran originalidad y profundidad analítica. La presente nota tiene por objeto examinar la estructura y alcance de esta escuela de pensamiento a través de sus referentes intelectuales, con el fin de evaluar el alcance de sus construcciones teóricas.

18

Amor-Coarasa, Alejandro, Monika Gruca, Sophie Hurez, Seza A. Gulec, Anthony McGoron, and John W. Babich. "Impact of elution impurities on DOTA and NOTA labeling with two commercial 68Ge/68Ga generators." Journal of Radioanalytical and Nuclear Chemistry 317, no. 3 (July 21, 2018): 1485–90. http://dx.doi.org/10.1007/s10967-018-6011-1.

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19

Blom, Elisabeth, Irina Velikyan, Azita Monazzam, Pasha Razifar, Manoj Nair, Payam Razifar, Jean-Luc Vanderheyden, et al. "Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers." Journal of Labelled Compounds and Radiopharmaceuticals 54, no. 11 (August 8, 2011): 685–92. http://dx.doi.org/10.1002/jlcr.1909.

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20

Anderegg, Giorgio, Francoise Arnaud-Neu, Rita Delgado, Judith Felcman, and Konstantin Popov. "Critical evaluation of stability constants of metal complexes of complexones for biomedical and environmental applications* (IUPAC Technical Report)." Pure and Applied Chemistry 77, no. 8 (January 1, 2005): 1445–95. http://dx.doi.org/10.1351/pac200577081445.

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Available experimental data on stability constants of proton (hydron) and metal complexes for seven complexones of particular biomedical and environmental interest: iminodiacetic acid [2,2'-azanediyldiacetic acid, IDA], (methylimino)diacetic acid [2,2'-(methylazanediyl)diacetic acid, MIDA]; 2,2',2'',2'''-{[(carboxymethyl)azanediyl]bis[(ethane-1,2-diyl)nitrilo]}tetraacetic acid (DTPA), 3,6,9,12-tetrakis(carboxymethyl)-3,6,9,12-tetraazatetradecanedioic acid (TTHA); 2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA); 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA); 2,2',2'',2'''-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetraacetic acid (TETA), published in 1945-2000, have been critically evaluated. Some typical errors in stability constant measurements for particular complexones are summarized. Higher quality data are selected and presented as “Recommended” or “Provisional”.

21

Kumar, Krishan, Michael Magerstädt, and Otto A. Gansow. "Lead(II) and bismuth(III) complexes of the polyazacycloalkane-N-acetic acids nota, dota, and teta." J. Chem. Soc., Chem. Commun., no. 3 (1989): 145–46. http://dx.doi.org/10.1039/c39890000145.

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22

Ray Banerjee, Sangeeta, Zhengping Chen, Mrudula Pullambhatla, Ala Lisok, Jian Chen, Ronnie C. Mease, and Martin G. Pomper. "Preclinical Comparative Study of 68Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA." Bioconjugate Chemistry 27, no. 6 (May 9, 2016): 1447–55. http://dx.doi.org/10.1021/acs.bioconjchem.5b00679.

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23

Hoareau, Raphaël, and Peter J. H. Scott. "Synthesis of perfluorinated analogs of DOTA and NOTA: bifunctional chelating groups with potential applications in hybrid molecular imaging." Tetrahedron Letters 54, no. 42 (October 2013): 5755–57. http://dx.doi.org/10.1016/j.tetlet.2013.08.035.

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24

Riondato, M., S. Pastorino, V. Duce, E. Giovannini, and A. Ciarmiello. "Comparative radium-223 labeling with NOTA and DOTA-somatostatin derivatives for a potential use in targeted cancer therapy." Nuclear Medicine and Biology 72-73 (July 2019): S50—S51. http://dx.doi.org/10.1016/s0969-8051(19)30328-2.

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25

Zhang, Yin, Hao Hong, Jonathan W. Engle, Jero Bean, Yunan Yang, Bryan R. Leigh, Todd E. Barnhart, and Weibo Cai. "Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA." PLoS ONE 6, no. 12 (December 9, 2011): e28005. http://dx.doi.org/10.1371/journal.pone.0028005.

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26

Botoso, Altamir. "A FOCALIZAÇÃO, O GÓTICO E O FANTÁSTICO EM A OUTRA VOLTA DO PARAFUSO, DE HENRY JAMES." Revista Guará - Revista de Linguagem e Literatura 10, no. 2 (April 15, 2021): 88. http://dx.doi.org/10.18224/gua.v10i2.8840.

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O propósito deste artigo é realizar uma análise do romance A outra volta do parafuso, do escritor norte-americano naturalizado britânico, Henry James, evidenciando alguns elementos de sua construção tais como a focalização e a presença de componentes oriundos do gótico e do fantástico, os quais permeiam o relato em primeira pessoa de uma preceptora, que vê ou imagina que existam fantasmas na mansão onde vai trabalhar. Como suporte teórico, são utilizados os estudos críticos de Bromwich (2011), Leite (2006), Lima (2017), Matos (2018), Parreira (2007), Piglia (2019), Santos (2011), Sylvestre (2012), Todorov (2007) e Vasconcelos (2002). Nota-se que a ambiguidade e a incerteza com a qual a voz narradora dota o relato fazem com que o enigma proposto não tenha resolução e, por isso mesmo, transformam esse romance de James numa das grandes obras da literatura ocidental, que intrigou e continua intrigando leitores e críticos de todas as épocas.

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Notni, Johannes, Karolin Pohle, and Hans-Jürgen Wester. "Comparative gallium-68 labeling of TRAP-, NOTA-, and DOTA-peptides: practical consequences for the future of gallium-68-PET." EJNMMI Research 2, no. 1 (2012): 28. http://dx.doi.org/10.1186/2191-219x-2-28.

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28

Lee, Jun-Young, Pyeong-Seok Choi, Seung-Dae Yang, and Jeong-Hoon Park. "TiO2 Decorated Low-Molecular Chitosan a Microsized Adsorbent for a 68Ge/68Ga Generator System." Molecules 26, no. 11 (May 26, 2021): 3185. http://dx.doi.org/10.3390/molecules26113185.

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We report column material for a 68Ge/68Ga generator with acid resistance and excellent adsorption and desorption capacity of 68Ge and 68Ga, respectively. Despite being a core element of the 68Ge/68Ga generator system, research on this has been insufficient. Therefore, we synthesized a low molecular chitosan-based TiO2 (LC-TiO2) adsorbent via a physical trapping method as a durable 68Ge/68Ga generator column material. The adsorption/desorption studies exhibited a higher separation factor of 68Ge/68Ga in the concentration range of HCl examined (0.01 M to 1.0 M). The prepared LC-TiO2 adsorbent showed acid resistance capabilities with >93% of 68Ga elution yield and 1.6 × 10−4% of 68Ge breakthrough. In particular, the labeling efficiency of DOTA and NOTA, by using the generator eluted 68Ga, was quite encouraging and confirmed to be 99.65 and 99.69%, respectively. Accordingly, the resulting behavior of LC-TiO2 towards 68Ge/68Ga adsorption/desorption capacity and stability with aqueous HCl exhibited a high potential for ion-exchange solid-phase extraction for the 68Ge/68Ga generator column material.

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Roosenburg, S., P. Laverman, L. Joosten, M. S. Cooper, P. K. Kolenc-Peitl, J. M. Foster, C. Hudson, et al. "PET and SPECT Imaging of a Radiolabeled Minigastrin Analogue Conjugated with DOTA, NOTA, and NODAGA and Labeled with 64Cu, 68Ga, and 111In." Molecular Pharmaceutics 11, no. 11 (July 11, 2014): 3930–37. http://dx.doi.org/10.1021/mp500283k.

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30

Miranda, Ana Claudia Camargo, Caiubi Rodrigues de Paula Santos, Leonardo Lima Fuscaldi, Fernanda Ferreira Mendonça, Solange Amorim Nogueira, Jorge Mejia, Akemi Osawa, Lilian Yuri Itaya Yamaga, Marycel Figols de Barboza, and Luciana Malavolta. "68GA-NOTA-UBI AND 68GA-DOTA-UBI AS RADIOPHARMACEUTICALS FOR THE DIAGNOSIS OF INFECTIOUS PROCESSES: PRECLINICAL STUDIES AND TRANSLATION TO CLINICAL APPLICATION." Hematology, Transfusion and Cell Therapy 46 (April 2024): S2—S3. http://dx.doi.org/10.1016/j.htct.2024.04.052.

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31

Xie, Qing, Teli Liu, Jing Ding, Nina Zhou, Xiangxi Meng, Hua Zhu, Nan Li, Jiangyuan Yu, and Zhi Yang. "Synthesis, preclinical evaluation, and a pilot clinical imaging study of [18F]AlF-NOTA-JR11 for neuroendocrine neoplasms compared with [68Ga]Ga-DOTA-TATE." European Journal of Nuclear Medicine and Molecular Imaging 48, no. 10 (February 25, 2021): 3129–40. http://dx.doi.org/10.1007/s00259-021-05249-8.

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32

Wienhoff, B. E., A. F. Prasanphanich, S. R. Lane, P. K. Nanda, R. P. Bandari, G. L. Sieckman та C. J. Smith. "Synthesis and Selective Radiolabeling Strategies for Production of [90Y-DOTA-βala-K-64Cu-NOTA-BBN(7–14) NH2] Conjugate; A Dual Negatron/Positron Emitting Radioligand". Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry 43, № 2 (28 грудня 2012): 178–84. http://dx.doi.org/10.1080/15533174.2012.731120.

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33

Malmberg, Jennie, Anna Perols, Zohreh Varasteh, Mohamed Altai, Alexis Braun, Mattias Sandström, Ulrike Garske, Vladimir Tolmachev, Anna Orlova, and Amelie Eriksson Karlström. "Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts." European Journal of Nuclear Medicine and Molecular Imaging 39, no. 3 (November 30, 2011): 481–92. http://dx.doi.org/10.1007/s00259-011-1992-9.

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34

Navarro, Anne-Sophie, Thomas Le Bihan, Patricia Le Saëc, Nathalie Le Bris, Clément Bailly, Catherine Saï-Maurel, Mickaël Bourgeois, Michel Chérel, Raphaël Tripier, and Alain Faivre-Chauvet. "TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model." Bioconjugate Chemistry 30, no. 9 (August 6, 2019): 2393–403. http://dx.doi.org/10.1021/acs.bioconjchem.9b00510.

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35

Cho, Yeonje, Armin Mirzapour-Kouhdasht, Hyosuk Yun, Jeong Hoon Park, Hye Jung Min, and Chul Won Lee. "Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability." International Journal of Molecular Sciences 23, no. 2 (January 10, 2022): 719. http://dx.doi.org/10.3390/ijms23020719.

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Radioactive isotopes are used as drugs or contrast agents in the medical field after being conjugated with chelates such as DOTA, NOTA, DTPA, TETA, CyDTA, TRITA, and DPDP. The N-terminal sequence of human serum albumin (HSA) is known as a metal binding site, such as for Co2+, Cu2+, and Ni2+. For this study, we designed and synthesized wAlb12 peptide from the N-terminal region of HSA, which can bind to cobalt, to develop a peptide-based chelate. The wAlb12 with a random coil structure tightly binds to the Co(II) ion. Moreover, the binding property of wAlb12 toward Co(II) was confirmed using various spectroscopic experiments. To identify the binding site of wAlb12, the analogs were synthesized by alanine scanning mutagenesis. Among them, H3A and Ac-wAlb12 did not bind to Co(II). The analysis of the binding regions confirmed that the His3 and α-amino group of the N-terminal region are important for Co(II) binding. The wAlb12 bound to Co(II) with Kd of 75 μM determined by isothermal titration calorimetry when analyzed by a single-site binding model. For the use of wAlb12 as a chelate in humans, its cytotoxicity and stability were investigated. Trypsin stability showed that the wAlb12 − Co(II) complex was more stable than wAlb12 alone. Furthermore, the cell viability analysis showed wAlb12 and wAlb12 + Co(II) to be non-toxic to the Raw 264.7 and HEK 293T cell lines. Therefore, a hot radioactive isotope such as cobalt-57 will have the same effect as a stable isotope cobalt. Accordingly, we expect wAlb12 to be used as a peptide chelate that binds with radioactive isotopes.

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Pattison, David A., and Rodney J. Hicks. "Molecular imaging in the investigation of hypoglycaemic syndromes and their management." Endocrine-Related Cancer 24, no. 6 (June 2017): R203—R221. http://dx.doi.org/10.1530/erc-17-0005.

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There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors (somatostatin receptors (SSTRs) and glucagon-like peptide-1 receptor (GLP-1R)) the amine precursor uptake and decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[18F]-l-fluoro-l-3,4-dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]fluoro-2-deoxy-d-glucose (FDG). Accurate preoperative localisation and staging is critical to enable directed surgical excision or enucleation with minimal morbidity and preservation of residual pancreatic function. Benign insulinoma has near ubiquitous dense GLP-1R expression enabling accurate localisation with radiolabelled-exendin-4 compounds (e.g.68Ga-NOTA-exendin-4 PET/CT), whilst the rarer and more difficult to manage metastatic insulinoma typically express SSTR and is preferably imaged with radiolabelled-SSTR analogues such as68Ga-DOTA-octreotate (DOTATATE) PET/CT for staging and assessment of suitability for peptide receptor radionuclide therapy (PRRT). Similar to other metastatic neuroendocrine tumours, FDG PET/CT is used in the setting of higher-grade metastatic insulinoma to provide important prognostic information that can guide treatment and determine suitability for PRRT. Interestingly, these three tracers appear to represent a spectrum of differentiation, which we conceptually describe as the ‘triple-flop’ phenomenon, with GLP-1R > SSTR > FDG in benign insulinoma and the opposite in higher-grade disease. This paper will review the clinical syndromes of adult hypoglycaemia (including a practical overview of the differential diagnoses to be considered), comparison of techniques for insulinoma localisation with emphasis on molecular imaging before discussing its implications for management of metastatic insulinoma.

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Guleria, Mohini, Tapas Das, Jeyachitra Amirdhanayagam, Haladhar D. Sarma, and Ashutosh Dash. "Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on Pharmacokinetics and Tumor Uptake in a Mouse Model." Cancer Biotherapy and Radiopharmaceuticals 33, no. 1 (February 2018): 8–16. http://dx.doi.org/10.1089/cbr.2017.2337.

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Ansari, Mohammad H., Mashood Ahmada, and Karel A. Dicke. "Synthesis of 2-(p-aminobenzyl) derivatives of 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-N,N′,N″,N″′-tetraacetic acid (DOTA): macrocyclic bifunctional chelating agents useful for antibodies labeling." Bioorganic & Medicinal Chemistry Letters 3, no. 6 (June 1993): 1067–70. http://dx.doi.org/10.1016/s0960-894x(00)80288-7.

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Cox, Jonathan P. L., Andrew S. Craig, Ian M. Helps, Karl J. Jankowski, David Parker, Michael A. W. Eaton, Andrew T. Millican, Kenneth Millar, Nigel R. A. Beeley, and Byron A. Boyce. "Synthesis of C- and N-functionalised derivatives of 1,4,7-triazacyclononane-1,4,7-triyltriacetic acid (NOTA), 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetrayltetra-acetic acid (DOTA), and diethylenenetriaminepenta-acetic acid (DTPA): bifunctional complexing agents for the derivatisation of antibodies." Journal of the Chemical Society, Perkin Transactions 1, no. 9 (1990): 2567. http://dx.doi.org/10.1039/p19900002567.

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40

IBRAHIM, FAISAL MAULANA, HOLIS ABDUL HOLIK, GHIFARI FARHAN HASIBUAN, and ACHMAD HUSSEIN SUNDAWA KARTAMIHARDJA. "MOLECULAR DOCKING AND ADMET PREDICTION OF 5-BENZYLOXYTRYPTOPHAN AS A POTENTIAL RADIOPHARMACEUTICAL KIT FOR MOLECULAR IMAGING OF CANCER." International Journal of Applied Pharmaceutics, December 11, 2021, 171–75. http://dx.doi.org/10.22159/ijap.2021.v13s4.43853.

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Objective: This in silico study aims to determine the inhibition effect of 5-BOTP with various bifunctional chelating agents (BFCA); NOTA, DOTA, TETA, CTPA, H2CB-DO2A, H2CBTE2A against the antiporter site of the LAT1. Methods: The research method consisted of the binding mode of 5-BOTP and its derivatives with LAT1, the docking score, the analysis of preADMET, and the overview of Ro5 compatibility. Results: The results showed that 5-BOTP-NOTA and 5-BOTP-DOTA had interactions with the gating residue (Phe252, Trp257, Asn258, and Tyr259) on the antiporter site of LAT1. 5-BOTP-NOTA and 5-BOTP-DOTA affinity are around-11.50 and-9.14 kcal/mol, respectively. Conclusion: Based on this study, 5-BOTP-NOTA and 5-BOTP-DOTA are the new compounds that have the potential as a theranostic agent of cancer by inhibiting LAT1.

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Xie, Qing, Wenyuan Zhou, Xiangxi Meng, Jin Ding, Dan Li, Ming Lu, Zhi Yang, and Jiangyuan Yu. "Somatostatin Receptor Imaging in Mice with Difference Positive Rate of SSTR2." Neuroendocrinology, November 4, 2023. http://dx.doi.org/10.1159/000535037.

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Introduction: Imaging with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 was performed to analyze differences among the three probes, and to analyze the correlation between the image and pathology parameters. Method: Tumor bearing mice with different positive rates of somatostatin receptor II (SSTR2) were established with HEK293-SSTR2 and HEK293 cells, and imaging was performed on the same mouse with [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-JR11 and [18F]AlF-NOTA-JR11 at 20, 60 and 120 min. The image parameters were obtained, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), standard deviation of SUVmean (SD), tumor volume and coefficient of variation (CoV). Immunohistochemistry of the tumor was performed after imaging to obtain positive rate of SSTR2. Statistical analysis was performed to analyze the differences among the three imaging techniques and the correlations between the relative imaging parameter and immunohistochemistry (IHC). Result: The SUVmax of [18F]AlF-NOTA-JR11 at 20 and 60 min was higher than that of [68Ga]Ga-DOTA-TATE (P=0.0015, 0.0035) and [68Ga]Ga-DOTA-JR11 (P=0.033, 0.019), and no significant difference was found in the other groups (P>0.05). There was a significant positive correlation between the positive rate and SUVmean of tumors with three tracers (P<0.05). However, a significant negative correlation between the positive rate and CoV was found only in the [68Ga]Ga-DOTA-TATE group at 60 min and 120 min (P=0.048, 0.026). Conclusion: [18F]AlF-NOTA-JR11 is more suitable for SSTR imaging within an hour than other two tracers. SUVmean of whole tumor can become an indicator for evaluating the positive rate of IHC, and the higher SUVmean of three tracers means a higher positive rate. However, the CoV is not applicable to the two antagonist tracers for evaluating the positive rate.

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Yang, Hua, Feng Gao, Brooke McNeil, Chengcheng Zhang, Zheliang Yuan, Stefan Zeisler, Joel Kumlin та ін. "Synthesis of DOTA-pyridine chelates for 64Cu coordination and radiolabeling of αMSH peptide". EJNMMI Radiopharmacy and Chemistry 6, № 1 (13 січня 2021). http://dx.doi.org/10.1186/s41181-020-00119-4.

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Abstract Background 64Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x = 1–4) that sequentially substitute carboxyl moieties with pyridyl moieties on a DOTA backbone. Results We found that the presence of pyridyl groups significantly increases 64Cu labeling conversion yield, with DOTA-2Py, −3Py and -4Py quantitatively complexing 64Cu at room temperature within 5 min (1 × 10− 4 M). [64Cu]Cu-DOTA-xPy (x = 2–4) exhibited good stability in human serum up to 24 h. When challenged with 1000 eq. of NOTA, no transmetallation was observed for all three 64Cu complexes. DOTA-xPy (x = 1–3) were conjugated to a cyclized α-melanocyte-stimulating hormone (αMSH) peptide by using one of the pendant carboxyl groups as a bifunctional handle. [64Cu]Cu-DOTA-xPy-αMSH retained good serum stability (> 96% in 24 h) and showed high binding affinity (Ki = 2.1–3.7 nM) towards the melanocortin 1 receptor. Conclusion DOTA-xPy (x = 1–3) are promising chelators for 64Cu. Further in vivo evaluation is necessary to assess the full potential of these chelators as a tool to enable further theranostic radiopharmaceutical development.

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HOLIK, HOLIS ABDUL, FAISAL MAULANA IBRAHIM, ABIB LATIFU FATAH, ARIFUDIN ACHMAD, and ACHMAD HUSSEIN SUNDAWA KARTAMIHARDJA. "IN SILICO STUDIES OF (S)-2-AMINO-4-(3,5-DICHLOROPHENYL) BUTANOIC ACID AGAINST LAT1 AS A RADIOTHERANOSTIC AGENT OF CANCER." International Journal of Applied Pharmaceutics, December 11, 2021, 239–43. http://dx.doi.org/10.22159/ijap.2021.v13s4.43868.

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Objective: This study aims to obtain a good activity of radiotheranostic kit for cancer which is built by combining (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) with various bifunctional chelators. Methods: This study was conducted through in silico method that consists of molecular docking simulation using AutoDock 4 as well as ADMET prediction using vNN-ADMET and Pre-ADMET. Six bifunctional chelators (i.e. CTPA, DOTA, H2CB-TE2A, H2CB-DO2A, NOTA, and TETA) were conjugated with ADPB as a carrier molecule and further analyzed through molecular docking and ADMET prediction. Results: The results showed that the ADPB-NOTA has the best affinity with the Gibbs free energy (ΔG) of-7.68 kcal/mol with an inhibition constant of 2.36 µM and its ability to bind with the gating residue of LAT1 (ASN258) through hydrogen interactions. Besides that, the ADPB-NOTA compound has a good ADME profile and is predicted to be safe for human use. Conclusion: This study showed that ADPB-NOTA is the most prospective candidate to be used as a radiotheranostic agent.

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Leupe, Hannes, Elin Pauwels, Timon Vandamme, Bliede Van den Broeck, Willem Lybaert, Jeroen Dekervel, Filip Van Herpe, et al. "Clinical impact of using [¹⁸F]AlF‐NOTA‐octreotide PET/CT instead of [⁶⁸Ga]Ga‐DOTA‐SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial." Journal of Neuroendocrinology, June 4, 2024. http://dx.doi.org/10.1111/jne.13420.

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Abstract[18F]AlF‐NOTA‐octreotide ([18F]AlF‐OC) is a promising alternative for [68Ga]Ga‐DOTA‐somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [18F]AlF‐OC PET/CT and [68Ga]Ga‐DOTA‐SSA PET/CT in the work‐up of neuroendocrine tumor (NET) patients. Patients who underwent both [18F]AlF‐OC and [68Ga]Ga‐DOTA‐TATE or [68Ga]Ga‐DOTA‐NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632–638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [68Ga]Ga‐DOTA‐SSA or [18F]AlF‐OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [18F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [68Ga]Ga‐DOTA‐SSA, the use of [18F]AlF‐OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [18F]AlF‐OC. The use of [18F]AlF‐OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [18F]AlF‐OC PET/CT as an alternative for [68Ga]Ga‐DOTA‐SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020–000549‐15.

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Mitran, Bogdan, Helge Thisgaard, Sara Rinne, Johan Hygum Dam, Frishta Azami, Vladimir Tolmachev, Anna Orlova, and Ulrika Rosenström. "Selection of an optimal macrocyclic chelator improves the imaging of prostate cancer using cobalt-labeled GRPR antagonist RM26." Scientific Reports 9, no. 1 (November 19, 2019). http://dx.doi.org/10.1038/s41598-019-52914-y.

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AbstractGastrin-releasing peptide receptors (GRPRs) are promising targets in oligometastatic prostate cancer. We have recently used 55Co (T1/2 = 17.5 h) as a label for next day PET imaging of GRPR expression obtaining high imaging contrast. The radionuclide-chelator combination can significantly influence the biodistribution of radiopeptides. Therefore, in this study, we hypothesized that the properties of 55Co-labeled PEG2-RM26 can be improved by identifying the optimal macrocyclic chelator. All analogues (X-PEG2-RM26, X = NOTA,NODAGA,DOTA,DOTAGA) were successfully labeled with radiocobalt with high yields and demonstrated high stability. The radiopeptides bound specifically and with picomolar affinity to GRPR and their cellular processing was characterized by low internalization. The best binding capacity was found for DOTA-PEG2-RM26. Ex vivo biodistribution in PC-3 xenografted mice was characterized by rapid blood clearance via renal excretion. Tumor uptake was similar for all conjugates at 3 h pi, exceeding the uptake in all other organs. Higher kidney uptake and longer retention were associated with N-terminal negative charge (DOTAGA-containing conjugate). Tumor-to-organ ratios increased over time for all constructs, although significant chelator-dependent differences were observed. Concordant with affinity measurements, DOTA-analog had the best retention of activity in tumors, resulting in the highest tumor-to-blood ratio 24 h pi, which translated into high contrast PET/CT imaging (using 55Co).

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Liu, Yang, Li Xia, Ping Cai, Yingwen Wang, Yue Feng, Wei Zhang, Nan Liu, Yue Chen, and Zhijun Zhou. "In vitro and in vivo comparative study of 68Ga-labeled DOTA-, NOTA-, and HBEDCC-chelated radiotracers targeting prostate-specific membrane antigen." Journal of Radioanalytical and Nuclear Chemistry, January 19, 2023. http://dx.doi.org/10.1007/s10967-022-08731-1.

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HOLIK, HOLIS ABDUL, ANGELA ELYSIA ELAINE, BERNAP DWI PUTRA SITINJAK, FAISAL MAULANA IBRAHIM, ARIFUDIN ACHMAD, B. S. ARI SUDARMANTO, HARYONO, and ACHMAD HUSSEIN SUNDAWA KARTAMIHARDJA. "META-TYROSINE CONJUGATES LABELED 64CU AND 68GA AS A CANCER RADIODIAGNOSIS AGENT USING MOLECULAR DOCKING SIMULATION ON LAT-1." International Journal of Applied Pharmaceutics, December 18, 2023, 163–68. http://dx.doi.org/10.22159/ijap.2023.v15s2.30.

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Objective: This in silico study aims to determine the most potential compound of meta-tyrosine (JX-075, JX-078, and JX-119) 64Cu and 68Ga conjugated with various bifunctional chelating agents, NOTA, DOTA, and NODAGA, against the antiporter site of the LAT1 as conduct to develop a cancer diagnostic compound. Methods: Molecular docking simulation was performed to investigate the interactions between meta-tyrosine compounds and LAT-1. Ligand compounds were drawn in 2D structures using ChemDraw Professional 16.0 and then labeled with 64Cu and 68Ga to build a radiopharmaceutical scaffold. The docking process was validated, characterized, and evaluated the interaction using several docking protocols in MOE 2020, a license owned by Gadjah Mada University. A visualization of the protein with the ligand was carried out on the BIOVIA Discovery Studio 2020. Results: Docking simulation results show that JX119 has greater potential due to lower bond energy, JX119_NODAGA_68Ga of-9.22 kcal/mol and JX119_NODAGA_64Cu of-9.09 kcal/mol. This compound showed interactions with transporter amino acid sites Tyr259 and Phe252, both JX-119_NODAGA 68Ga and JX119_NODAGA_64Cu. Conclusion: The compounds [64Cu]Cu-NODAGA-JX119 and [68Ga]Ga-NODAGA-JX119 are the most potential compounds with the lowest (most negative) Gibbs energy as conduct to develop a diagnostic compound.

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Pauwels, Elin, Frederik Cleeren, Térence Tshibangu, Michel Koole, Kim Serdons, Lennert Boeckxstaens, Jeroen Dekervel, et al. "¹⁸F-AlF-NOTA-octreotide outperforms⁶⁸Ga-DOTA-TATE/-NOC PET in neuroendocrine tumor patients: results from a prospective, multicenter study." Journal of Nuclear Medicine, October 20, 2022, jnumed.122.264563. http://dx.doi.org/10.2967/jnumed.122.264563.

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COX, J. P. L., A. S. CRAIG, I. M. HELPS, K. J. JANKOWSKI, D. PARKER, M. A. W. EATON, A. T. MILLICAN, K. MILLAR, N. R. A. BEELEY, and B. A. BOYCE. "ChemInform Abstract: Synthesis of C- and N-Functionalised Derivatives of 1,4,7-Triazacyclononane-1,4,7-triyltriacetic Acid (NOTA), 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayltetraacetic Acid (DOTA), and Diethylenenetriaminepentaacetic Acid (DTPA): Bif." ChemInform 21, no. 52 (December 25, 1990). http://dx.doi.org/10.1002/chin.199052222.

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Bao, Guangfa, Ziqiang Wang, Luoxia Liu, Buchuan Zhang, Shuang Song, Dongdong Wang, Siyuan Cheng, et al. "Targeting CXCR4/CXCL12 axis via [177Lu]Lu-DOTAGA.(SA.FAPi)2 with CXCR4 antagonist in triple-negative breast cancer." European Journal of Nuclear Medicine and Molecular Imaging, April 8, 2024. http://dx.doi.org/10.1007/s00259-024-06704-y.

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Abstract Purpose Radiopharmaceutical therapies targeting fibroblast activation protein (FAP) have shown promising efficacy against many tumor types. But radiopharmaceuticals alone in most cases are insufficient to completely eradicate tumor cells, which can partially be attributed to the protective interplay between tumor cells and cancer-associated fibroblasts (CAFs). The C-X-C chemokine receptor type 4/C-X-C motif chemokine 12 (CXCR4/CXCL12) interaction plays an important role in orchestrating tumor cells and CAFs. We hereby investigated the feasibility and efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2, a FAP-targeting radiopharmaceutical, in combination with AMD3100, a CXCR4 antagonist, in a preclinical murine model of triple-negative breast cancer (TNBC). Methods Public database was first interrogated to reveal the correlation between CAFs’ scores and the prognosis of TNBC patients, as well as the expression levels of FAP and CXCR4 in normal tissues and tumors. In vitro therapeutic efficacy regarding cell proliferation, migration, and colony formation was assessed in BALB/3T3 fibroblasts and 4T1 murine breast cancer cells. In vivo therapeutic efficacy was longitudinally monitored using serial 18F-FDG, [18F]AlF-NOTA-FAPI-04, and [68Ga]Ga-DOTA-Pentixafor PET/CT scans and validated using tumor sections through immunohistochemical staining of Ki-67, α-SMA, CXCR4, and CXCL12. Intratumoral abundance of myeloid-derived suppressive cells (MDSCs) was analyzed using flow cytometry in accordance with the PET/CT schedules. Treatment toxicity was evaluated by examining major organs including heart, lung, liver, kidney, and spleen. Results CAFs’ scores negatively correlated with the survival of TNBC patients (p < 0.05). The expression of CXCR4 and FAP was both significantly higher in tumors than in normal tissues. The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 significantly suppressed cell proliferation, migration, and colony formation in cell culture, and exhibited synergistic effects in 4T1 tumor models along with a decreased number of MDSCs. PET/CT imaging revealed lowest tumor accumulation of 18F-FDG and [18F]AlF-NOTA-FAPI-04 on day 13 and day 14 after treatment started, both of which gradually increased at later time points. A similar trend was observed in the IHC staining of Ki-67, α-SMA, and CXCL12. Conclusion The combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and AMD3100 is a feasible treatment against TNBC with minimal toxicity in main organs.