Dataset Information

Evaluation of Pan-SSTRs Targeted Radioligand [⁶⁴Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice.

ABSTRACT: ⁶⁴Cu-labeled new pan-somatostatin receptors (pan-SSTRs) probe PA1 was synthesized, characterized, and evaluated by in vitro and in vivo experiments. [⁶⁴Cu]NOTA-PA1 was obtained with high specific activity, high radiochemical purity, and good stability. Cell uptake of [⁶⁴Cu]NOTA-PA1 was higher than that of [⁶⁴Cu]DOTA-TATE in MCF-7, A549, BGC823, and HT-29 cell lines. [⁶⁴Cu]NOTA-PA1 showed high binding affinity for SSTRs expressed in A549 cells. The in vivo biodistribution and micropositron emission tomography (micro-PET) imaging studies of [⁶⁴Cu]NOTA-PA1 revealed good detection ability in MCF-7 and A549 xenografted nude mice. The radiosynthesis, quality control, and preliminary biological evaluation of [⁶⁴Cu]NOTA-PA1 have broaden the application of radiolabeled octreotide for SSTRs imaging, which could act as a potential multisubtypes targeted radiotracer for imaging SSTRs-positive tumors.

SUBMITTER: Liu F

PROVIDER: S-EPMC7153030 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Evaluation of Pan-SSTRs Targeted Radioligand [64Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice.

Liu Fei F Guo Xiaoyi X Liu Teli T Xu Xiaoxia X Li Nan N Xiong Chiyi C Li Chun C Zhu Hua H Yang Zhi Z

ACS medicinal chemistry letters 20200212 4

64Cu-labeled new pan-somatostatin receptors (pan-SSTRs) probe PA1 was synthesized, characterized, and evaluated by in vitro and in vivo experiments. [64Cu]NOTA-PA1 was obtained with high specific activity, high radiochemical purity, and good stability. Cell uptake of [64Cu]NOTA-PA1 was higher than that of [64Cu]DOTA-TATE in MCF-7, A549, BGC823, and HT-29 cell lines. [64Cu]NOTA-PA1 showed high binding affinity for SSTRs expresse ...[more]

PMID: 32292548

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Project description:Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

Project description:IntroductionRecent studies showed the presence of microplastic in human lungs. There remains an unmet need to identify the biodistribution of microplastic after inhalation. In this study, we traced the biodistribution of inhaled micro-sized polystyrene (mPS) and/or nano-sized PS (nPS) using 64Cu with PET in mice.MethodsWe used 0.2-0.3-µm sized mPS and 20-nm sized nPS throughout. 64Cu-DOTA-mPS, 64Cu-DOTA-nPS and/or 64CuCl2 were used to trace the distribution in the murine inhalation model. PET images were acquired using an INVEON PET scanner at 1, 12, 24, 48, and 72 h after intratracheal instillation, and the SUVmax for interesting organs were determined, biodistribution was then determined in terms of percentage injected dose/gram of tissue (%ID/g). Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of 64Cu-DOTA-PS in tissue.ResultsPET image demonstrated that the amount of 64Cu-DOTA-mPS retained within the lung was significantly higher than 64Cu-DOTA-nPS until 72 h; SUVmax values of 64Cu-DOTA-mPS in lungs was 11.7 ± 5.0, 48.3 ± 6.2, 65.5 ± 2.3, 42.2 ± 13.1, and 13.2 ± 2.3 at 1, 12, 24, 48, and 72 h respectively whereas it was 31.2 ± 3.1, 17.3 ± 5.9, 10.0 ± 3.4, 8.1 ± 2.4 and 8.9 ± 3.6 for 64Cu-DOTA-nPS at the corresponding timepoints. The biodistribution data supported the PET data with a similar pattern of clearance of the radioactivity from the lung. nPS cleared rapidly post instillation in comparison to mPS within the lungs. Higher accumulation of %ID/g for nPS (roughly 2 times) were observed compared to mPS in spleen, liver, intestine, thymus, kidney, brain, salivary gland, ovary, and urinary bladder. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from 64Cu-DOTA-mPS or nPS.ConclusionPET image demonstrated the differences in accumulations of mPS and/or nPS between lungs and other interesting organs. The information provided may be used as the basis for future studies on the toxicity of mPS and/or nPS.

Dataset Information

Evaluation of Pan-SSTRs Targeted Radioligand [⁶⁴Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice.

Publications

Evaluation of Pan-SSTRs Targeted Radioligand [<sup>64</sup>Cu]NOTA-PA1 Using Micro-PET Imaging in Xenografted Mice.

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