Estimation of human absorbed dose for [113mIn]In-AMBA using animal experimental data and Monte Carlo simulation

Document Type : Original Article

Authors

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

Abstract

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 DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2 (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 [113mIn]In-AMBA, based on preclinical biodistribution data and Monte Carlo simulations.
Methods: AMBA peptide was radiolabeled with 113mIn prepared from an in-house developed 113Sn/113mIn generator. Biodistribution studies were performed in rats at multiple time points following the injection of [113mIn]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 [113mIn]In-AMBA exceeded 98% (HPLC). Biodistribution studies demonstrated high cumulation of activity in the GRPR-expressing organs and kidneys. The highest absorbed doses were observed in the pancreas (0.0044 mGy/MBq), and kidneys (0.0018 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 (≤ 0.001 mGy/MBq).
Conclusion: This study demonstrates that [113mIn]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 [113mIn]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.

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References

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