Evaluation of a novel 68Ga radiolabeled ligand targeting glutamate carboxypeptide II in an animal model of breast cancer

Abstract

Aim: This study aims to pre-clinically investigate the accumulation of [68Ga]Ga-DKFZ-PSMA-11, a glutamate carboxypeptidase II ligand that was previously reported in advanced stages of breast cancer in humans, in different breast cancer xenograft mice, in order to better understand the accumulation of [68Ga] Ga-DKFZ-PSMA-11. Material and Methods: MCF-7, MDA-MB-231 and LNCaP athymic nude mice xenografts were developed by inoculating either MCF-7 cells suspension (DMEM/ Matrigel (1:1)) subcutaneously in the hind-right flank of the mice, MDA-MB-231 cells (PBS/ Matrigel (1:1)) inoculated into the mammary fat pad in the abdominal region or LNCaP cell suspension (PBS/ Matrigel (1:1)) subcutaneously into the hind-right flank of the mice. [68Ga]Ga-DKFZ-PSMA-11 was optimised for suitable administration into mice. On day one, MCF-7 and MDA-MB-231 female athymic nude mice were imaged with [18F]FDG-micro-PET/CT, and day two, with [68Ga]Ga-DKFZ-PSMA-11-micro-PET/CT followed by ex vivo biodistribution. Results: The radiolabelled [68Ga]Ga-DKFZ-PSMA-11 was purified by solid phase extraction using Sep-Pak C18-light cartridge, an ethanol concentration of 25% in saline with a volume of 0.3 ml demonstrated a radiochemical yield of ~ 69% and radiochemical purity of >96.9% (n = 5). Radiochemical yield (n = 7) was 165 ± 70 MBq [68Ga]Ga-DKFZ-PSMA-11. Female athymic nude mice (n = 4) with MCF-7 tumours measured 136 ± 100 mm3 prior to [18F]FDG-micro-PET/CT and 167 ± 83 mm3 prior to [68Ga]Ga-DKFZ-PSMA-11-micro-PET/CT. The MCF-7 xenografts performed micro-PET/CT following injection with [18F]FDG-day 1 (7 ± 2 MBq) and [68Ga]Ga-DKFZ-PSMA-11-day 2 (14 ± 4 MBq). Female athymic nude mice xenografts (n = 5) with MDA-MB-231 tumours measured 150 ± 31 mm3 prior to [18F]FDG-micro-PET/CT and 191 ± 19 mm3 prior to [68Ga]Ga-DKFZPSMA-11-micro-PET/CT. The MDA-MB-231 xenografts performed micro-PET/CT following injection with [18F]FDG-day 1 (11 ± 2 MBq) and [68Ga]Ga-DKFZ-PSMA-11-day 2 (14 ± 2 MBq). There were no LNCaP xenografts imaged due to failure to develop the model. MCF-7 tumours did not show accumulation of both [18F]FDG and [68Ga]Ga-DKFZ-PSMA-11. MDA-MB-231 tumours accumulated [18F]FDG and did not accumulate [68Ga]Ga-DKFZ-PSMA-11. Conclusion: The study reports on MCF-7 and MDA-MB-231 xenografts imaged with [68Ga]Ga-DKFZ-PSMA-11 or [18F]FDG. There was no accumulation of [68Ga]Ga-DKFZ-PSMA-11 in both the MCF-7 and MDA-MB-231 tumour. Enhanced permeability and retention effects might be responsible for tracer uptake, since clinical studies shown that accumulation of [68Ga]Ga-DKFZ-PSMA-11correlates to pathologic neo-vasculature found in solid tumours.