Abstract 2540: Biodistribution and dosimetry of FAPI-46 in mouse model of colorectal carcinoma with PET and SPECT imaging

Abstract Fibroblast Activation Protein (FAP) is overexpressed in cancer-associated fibroblasts of many epithelial cancers. In nonmalignant conditions FAP is overexpressed in wounds healing, inflammatory and fibrotic tissues, whereas in healthy adult tissue FAP expression is low. Radiolabeled FAP Inhibitors (FAPIs) are used in clinic for imaging and/or radiotherapy. FAPIs are usually conjugated to a DOTA chelating site which allows the use of both diagnostic and therapeutic radionuclides. In this study we investigated the radiochemical properties, pharmacokinetics and dosimetry of FAPI-46 in after Lu-177 or Ga-68 labelling in preclinical mouse model of colorectal carcinoma. FAPI-46 (non-GMP grade) was radiolabeled with Ga-68 and Lu-177 using previous described synthesis with slight modifications (Loktev et al., J Nucl Med 2019). Radiochemical purity was determined with radio-HPLC (LabLogic). A colon cancer mouse model was created by inoculating 5x106 HCT116 cells in 100 µl 50% matrigel subcutaneously (s.c.) in the interscapular area of NMRI-Foxn1nu male mice. Approximately two weeks post inoculation, animals were randomized into groups based on tumor volume (n = 2-4 / timepoint). Animals were dosed with 177Lu-FAPI-46 or 68Ga-FAPI-46, scanned with SPECT (Mediso) or PET (Sedecal) up to 90 minutes. Simultaneously satellite animals were terminated and sampled for gamma counting (Perkin Elmer) at 30-, 60- and 90-minutes post injection. Image analysis was performed with PMOD software. Dosimetry calculations will be performed with OLINDA 2.0. 68Ga- and 177Lu-FAPI-46 were produced with high radiochemical yield and purity. Nuclear imaging of radiolabeled FAPI-46 with both radiolabels shows fast kinetics and excretion via kidney as shown in literature. The dosimetry calculations are still ongoing. FAPI is suitable for multipurpose imaging and there is a great interest towards this molecule in the fields of imaging and oncology. The same precursor structure can be labeled with more than one radionuclide with high radiochemical yield and purity. Citation Format: Johanna Rokka, Henrik Vaherto, Susanne Bäck, Jussi Rytkönen. Biodistribution and dosimetry of FAPI-46 in mouse model of colorectal carcinoma with PET and SPECT imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2540.