Preclinical assessment of 68Ga ‐PSMA‐617 entrapped in a microemulsion delivery system for applications in prostate cancer PET/CT imaging

It has in recent years been reported that microemulsion (ME) delivery systems provide an opportunity to improve the efficacy of a therapeutic agent whilst minimising side effects and also offer the advantage of favourable treatment regimens. The prostate ‐specific membrane antigen (PSMA) targeting agents PSMA‐11 and PSMA‐617, which accumulate in prostate tumours, allows for [68Ga]Ga3+‐radiolabelling and PET imaging of PSMA‐expressionin vivo. We herein report the formulation of [68Ga]Ga ‐PSMA‐617 into a ME ≤40 nm including its evaluation for improved cellular toxicity andin vivo biodistribution.The [68Ga]Ga ‐PSMA‐617‐ME was testedin vitro for its cytotoxicity to HEK293 and PC3 cells. [68Ga]Ga ‐PSMA‐617‐ME was administered intravenously in BALB/c mice followed by microPET/CT imaging andex vivo biodistribution determination.[68Ga]Ga ‐PSMA‐617‐ME indicated negligible cellular toxicity at different concentrations. A statistically higher tolerance towards the [68Ga]Ga ‐PSMA‐617‐ME occurred at 0.125mg/ml by HEK293 cells compared to PC3 cells. The biodistribution in wild‐type BALB/C mice showed the highest amounts of radioactivity (%ID/g) presented in the kidneys (31%) followed by the small intestine (10%) and stomach (9%); the lowest uptake was seen in the brain (0.5%).The incorporation of [68Ga]Ga ‐PSMA‐617 into ME was successfully demonstrated and resulted in a stable non‐toxic formulation as evaluated byin vitro andin vivo means.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research