Evaluation of 47Sc- labeled Gastrin Releasing Peptide-based Radiotracers for Prostate and Breast Cancer

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Ziel/Aim: Gastrin-releasing peptide receptor (GRPr) radioantagonists represent a promising approach for imaging and targeted radionuclide cancer therapy. GRPr is overexpressed in various malignancies including prostate and breast cancer, making it an attractive target for cancer management. The goal of the current study was to assess the potential of a 47 Sc-labeled GRPr-based radioantagonist to serve as a therapeutic radiotracer for prostate and breast cancer. Methodik/Methods: A statine-based GRPr antagonist (AAZTA 5 -Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 : LF1) was radiolabeled with scandium-47. Detailed in-vitro evaluation, including metabolic stability, saturation and internalization studies, was carried out in PC3 and T47D cancer cells. Biodistribution studies and SPECT/CT imaging were performed in PC3 and T47D xenografts. The radiotherapeutic efficacy of [ 47 Sc]Sc-LF1 was investigated in PC3 xenografts via tumor regression studies. Ergebnisse/Results: [ 47 Sc]Sc-LF1 was prepared in high radiochemical purity (> 99%) with molar activities up to 40 MBq/nmol. [ nat/47 Sc]Sc-LF1 exhibited affinity for both PC3 and T47D cells, with K d values of 6.9±2.3 nM and 10.6±3.0 nM respectively, and a low internalization rate with values below 10% in relation to the total cell bound activity. The metabolite analysis revealed the formation of three hydrophilic metabolites. In PC3 xenografts, [ 47 Sc]Sc-LF1 exhibited high, retained and specific tumor uptake, with values of 24.1±2.1 and 4.8±1.6% I.A./g at 1 and 72 h p.i., respectively. The lower density of GRPr in the T47D xenografts resulted in tumor uptake of 9.5±2.5 and 0.7±0.1% I.A./g at 1 and 72 h p.i., respectively. The clearance of the radioactivity from pancreas was significantly faster compared to the tumor uptake. The favorable pharmacokinetic performance of [ 47 Sc]Sc-LF1 also led to SPECT/CT images of high contrast. Significant reduction in tumor volume and increase in survival rate confirms the radiotherapeutic efficacy of [ 47 Sc]Sc-LF1 in PC3 xenografts. Schlussfolgerungen/Conclusions: The high and persistent tumor uptake in two cancer entities with elevated expression of GRPr and the tumor response (tumor size and survival rate) underscores the significant potential of [47Sc]Sc-LF1 as a dual purpose tool for both SPECT imaging and targeted therapy. Publication History Article published online: 12 March 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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