18F-Labeled Cyclized α-Melanocyte-Stimulating Hormone Derivatives for Imaging Human Melanoma Xenograft with Positron Emission Tomography
| Autor: | David M. Perrin, Navjit Hundal-Jabal, Nadine Colpo, Jutta Zeisler, Francois Benard, Helen Merkens, Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Biodistribution
Melanocyte-stimulating hormone Cell lcsh:Medicine Article 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine medicine Receptor lcsh:Science Melanoma Multidisciplinary medicine.diagnostic_test Chemistry lcsh:R medicine.disease Imaging agent medicine.anatomical_structure Positron emission tomography 030220 oncology & carcinogenesis Cancer research lcsh:Q Cancer imaging Melanocortin 1 receptor |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Since metastatic melanoma is deadly, early diagnosis thereof is crucial for managing the disease. We recently developed α-melanocyte-stimulating hormone (αMSH) derivatives, [68Ga]Ga-CCZ01048 and [18F]CCZ01064, that target the melanocortin 1 receptor (MC1R) for mouse melanoma imaging. In this study, we aim to evaluate [18F]CCZ01064 as well as a novel dual-ammoniomethyl-trifluoroborate (AmBF3) derivative, [18F]CCZ01096, for targeting human melanoma xenograft using μPET imaging. The peptides were synthesized on solid phase using Fmoc chemistry. Radiolabeling was achieved in a one-step 18F-19F isotope-exchange reaction. μPET imaging and biodistribution studies were performed in NSG mice bearing SK-MEL-1 melanoma xenografts. The MC1R density on the SK-MEL-1 cell line was determined to be 972 ± 154 receptors/cell (n = 4) via saturation assays. Using [18F]CCZ01064, moderate tumor uptake (3.05 ± 0.47%ID/g) and image contrast were observed at 2 h post-injection. Molar activity was determined to play a key role. CCZ01096 with two AmBF3 motifs showed comparable sub-nanomolar binding affinity to MC1R and much higher molar activity. This resulted in improved tumor uptake (6.46 ± 1.42%ID/g) and image contrast (tumor-to-blood and tumor-to-muscle ratios were 30.6 ± 5.7 and 85.7 ± 11.3, respectively) at 2 h post-injection. [18F]CCZ01096 represents a promising αMSH-based μPET imaging agent for human melanoma and warrants further investigation for potential clinical translation. |
| Databáze: | OpenAIRE |
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