First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma
Abstract Melanoma remains one of the leading causes of cancer-related mortality worldwide, necessitating advanced imaging techniques for early and accurate detection. This study assesses the dosimetry, safety, and imaging performance of a novel 68Ga-labeled α-melanocyte-stimulating hormone ([68Ga]Ga...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-02334-y |
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| author | Samaneh Zolghadri Mohsen Bakhshi Kashi Nasim Vahidfar Saeed Farzanefar Arezou Karimian Mohammad Hossein Mohammadi Ashnani Hassan Yousefnia |
| author_facet | Samaneh Zolghadri Mohsen Bakhshi Kashi Nasim Vahidfar Saeed Farzanefar Arezou Karimian Mohammad Hossein Mohammadi Ashnani Hassan Yousefnia |
| author_sort | Samaneh Zolghadri |
| collection | DOAJ |
| description | Abstract Melanoma remains one of the leading causes of cancer-related mortality worldwide, necessitating advanced imaging techniques for early and accurate detection. This study assesses the dosimetry, safety, and imaging performance of a novel 68Ga-labeled α-melanocyte-stimulating hormone ([68Ga]Ga-αMSH) derivative for targeting melanocortin 1 receptors (MC1Rs) in metastatic melanoma. In this first-in-human, prospective, open-label clinical trial, 11 patients with histologically confirmed metastatic melanoma underwent whole-body PET/CT imaging following intravenous administration of the radiolabeled compound (150 ± 10 MBq). Tumor uptake, biodistribution, pharmacokinetics, and radiation dosimetry were evaluated at 60 and 120 min post-injection. Organ and tumor uptake values were measured as standardized uptake values. Radiation dose estimates were calculated using the MIRD methodology and S-values obtained from OLINDA/EXM software. Safety evaluations included monitoring adverse events, biochemical parameters, and vital signs. The radiopharmaceutical demonstrated rapid and selective uptake in metastatic melanoma lesions, achieving high tumor-to-background contrast within 60 min. Quantitative analysis showed substantial tumor uptake, with sustained activity at 120 min. High tumor-to-blood and tumor-to-muscle ratios ensured excellent lesion detectability. The kidneys exhibited the highest absorbed dose (0.0948 ± 0.0425 mSv/MBq), attributed to renal excretion, whereas the brain received the lowest dose (0.0012 ± 0.0007 mSv/MBq). Comparisons with [18F]FDG and other tracers demonstrated superior dosimetry profiles, minimizing radiation exposure and enabling repeat imaging. Also, safety monitoring revealed no serious adverse events. [68Ga]Ga-αMSH analogue exhibits excellent imaging properties, favorable pharmacokinetics, and a strong safety profile, supporting its clinical utility for PET imaging of metastatic melanoma. Its high tumor specificity and minimal off-target accumulation address limitations associated with [18F]FDG. |
| format | Article |
| id | doaj-art-e35c146ae6534a418646b695e8020c38 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e35c146ae6534a418646b695e8020c382025-08-20T03:48:18ZengNature PortfolioScientific Reports2045-23222025-05-0115111010.1038/s41598-025-02334-yFirst-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanomaSamaneh Zolghadri0Mohsen Bakhshi Kashi1Nasim Vahidfar2Saeed Farzanefar3Arezou Karimian4Mohammad Hossein Mohammadi Ashnani5Hassan Yousefnia6Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical SciencesDepartment of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical SciencesDepartment of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical SciencesRadiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)Department of Environmental Science and Engineering, Faculty of Agriculture and Environment, Arak UniversityRadiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)Abstract Melanoma remains one of the leading causes of cancer-related mortality worldwide, necessitating advanced imaging techniques for early and accurate detection. This study assesses the dosimetry, safety, and imaging performance of a novel 68Ga-labeled α-melanocyte-stimulating hormone ([68Ga]Ga-αMSH) derivative for targeting melanocortin 1 receptors (MC1Rs) in metastatic melanoma. In this first-in-human, prospective, open-label clinical trial, 11 patients with histologically confirmed metastatic melanoma underwent whole-body PET/CT imaging following intravenous administration of the radiolabeled compound (150 ± 10 MBq). Tumor uptake, biodistribution, pharmacokinetics, and radiation dosimetry were evaluated at 60 and 120 min post-injection. Organ and tumor uptake values were measured as standardized uptake values. Radiation dose estimates were calculated using the MIRD methodology and S-values obtained from OLINDA/EXM software. Safety evaluations included monitoring adverse events, biochemical parameters, and vital signs. The radiopharmaceutical demonstrated rapid and selective uptake in metastatic melanoma lesions, achieving high tumor-to-background contrast within 60 min. Quantitative analysis showed substantial tumor uptake, with sustained activity at 120 min. High tumor-to-blood and tumor-to-muscle ratios ensured excellent lesion detectability. The kidneys exhibited the highest absorbed dose (0.0948 ± 0.0425 mSv/MBq), attributed to renal excretion, whereas the brain received the lowest dose (0.0012 ± 0.0007 mSv/MBq). Comparisons with [18F]FDG and other tracers demonstrated superior dosimetry profiles, minimizing radiation exposure and enabling repeat imaging. Also, safety monitoring revealed no serious adverse events. [68Ga]Ga-αMSH analogue exhibits excellent imaging properties, favorable pharmacokinetics, and a strong safety profile, supporting its clinical utility for PET imaging of metastatic melanoma. Its high tumor specificity and minimal off-target accumulation address limitations associated with [18F]FDG.https://doi.org/10.1038/s41598-025-02334-y |
| spellingShingle | Samaneh Zolghadri Mohsen Bakhshi Kashi Nasim Vahidfar Saeed Farzanefar Arezou Karimian Mohammad Hossein Mohammadi Ashnani Hassan Yousefnia First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma Scientific Reports |
| title | First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma |
| title_full | First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma |
| title_fullStr | First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma |
| title_full_unstemmed | First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma |
| title_short | First-in-human dosimetry and safety evaluation of 68Ga-αMSH derivative for PET imaging of melanoma |
| title_sort | first in human dosimetry and safety evaluation of 68ga αmsh derivative for pet imaging of melanoma |
| url | https://doi.org/10.1038/s41598-025-02334-y |
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