Preparation and preclinical study of [68Ga]‌Ga-(Pip)-Nle-CycMSHhex: Optimized production with an in-house 68Ge/68Ga generator

Document Type : Original Article

Authors

1 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

2 Nuclear Engineering Department, Shiraz University, Shiraz, Iran

3 Faculty of Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran

Abstract

Introduction: The early diagnosis of melanoma is crucial for treatment and management of this aggressive malignancy.   The present study describes the preparation and preclinical evaluation of 68Ga-radiolabeled DOTA-4amino-(I-carboxymethyl) piperidine (Pip)-Nle-cysMSHhex peptide ([68Ga]Ga-CCZ01048) as a potential aide for PET imaging and early diagnosis of malignant melanoma.
Methods: Various parameters were assessed to optimize the final preparation processes. The radiochemical purity of the final complex was checked using RTLC and HPLC methods. The stability of the radiolabeled complex was studied at 15, 30, 60 and 120-min post-injection. The partition coefficient was also studied. Cellular studies of the labeled peptide were measured using B16F10 cells at different post-treatment intervals. The biodistribution of the labeled compound was evaluated using normal and tumor-bearing mice.
Results: [68Ga]­Ga-(Pip)-Nle-cysMSHhex radiolabeled complex was prepared with a specific activity of 118.4 TBq/mmol and radiochemical purity > 99% at optimized conditions. The results of stability studies show that the radiolabeled compound is stable in PBS buffer and human serum after 120 min. The cellular studies demonstrated that a binding affinity of [68Ga]­Ga-(Pip)-Nle-cysMSHhex on B16F10 cells and the internalization of the complex increased from about 31% in 30 min to 62% in 240 min post-treatment. The biodistribution studies showed excretion of major portion of the tracer through the kidneys. The remainder of the tracer mostly accumulated at the tumor site. No significant uptake in non-target organs was observed at any interval following injection.
Conclusion: The [68Ga]­Ga-(Pip)-Nle-cysMSHhex radiolabeled complex has the potential as a PET imaging agent for evaluation of metastatic malignant melanoma.

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Main Subjects

References

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