Estimation of human absorbed dose for [۱۱۳mIn]In-AMBA using animal experimental data and Monte Carlo simulation

Introduction: Gastrin-releasing peptide receptors (GRPRs) are overexpressed in a wide range of malignancies, making them attractive targets for molecular imaging and targeted therapy. The bombesin analog DO۳A-CH۲CO-G-[۴-aminobenzoyl]-QWAVGHLM-NH۲ (AMBA), has demonstrated promising potential in both diagnostic and therapeutic applications by selectively binding to GRPRs. This study aimed to estimate the absorbed dose of [۱۱۳mIn]In-AMBA, based on preclinical biodistribution data and Monte Carlo simulations.Methods: AMBA peptide was radiolabeled with ۱۱۳mIn prepared from an in-house developed ۱۱۳Sn/۱۱۳mIn generator. Biodistribution studies were performed in rats at multiple time points following the injection of [۱۱۳mIn]In-AMBA. The accumulated activity in each rat organ was extrapolated to human organ.  Finally, the absorbed doses in human organs were estimated by applying the Monte Carlo N-Particle (MCNP) software in Oak Ridge National Laboratory (ORNL) phantom using the Medical Internal Radiation Dose (MIRD) method.Results: The radiochemical purity (RCP) of [۱۱۳mIn]In-AMBA exceeded ۹۸% (HPLC). Biodistribution studies demonstrated high cumulation of activity in the GRPR-expressing organs and kidneys. The highest absorbed doses were observed in the pancreas (۰.۰۰۴۴ mGy/MBq), and kidneys (۰.۰۰۱۸ mGy/MBq), respectively. In contrast, non-target organs exhibited minimal uptake and rapid clearance from the animal body results in minimal absorbed dose in non-target organs (≤ ۰.۰۰۱ mGy/MBq).Conclusion: This study demonstrates that [۱۱۳mIn]In-AMBA is a safe and promising SPECT imaging agent for the detection of GRPR-positive tumors. While current findings support the safety and potential of [۱۱۳mIn]In-AMBA as a GRPR-targeted SPECT agent, further validation in tumor-bearing animal models and early-phase clinical studies is required for clinical translation.

کلیدواژه ها:

[۱۱۳mIn]In-AMBA ، Monte Carlo ، ORNL ، MIRD ، S-value