Imaging matrix metalloproteinase activity with RP782 in detection of tumor in mouse tumor models

1134 Objectives Elevated matrix metalloproteinase (MMP) activity has been identified in tumors with multiple origins. RP782 is an investigational pan-MMP inhibitor radiolabeled with 111In for imaging MMP activity. This study was to investigate the correlation of 111In-RP782 tumor uptake in-vivo with tumor MMP activity measured ex-vivo, and to determine if 111In-RP782 imaging could be used in tumor detection. Methods Transgenic c-neu oncomice and xenograft mouse models were used at 3 weeks after inoculation with human fibrosarcoma cells (HT-1080) and rat pheochromocytoma (PC-12). To measure tissue MMP activity levels ex-vivo, tumors were harvested from these mice and MMP-2 and -9 activity levels in the tumor tissues were measured using the Biotrack MMP assay kit. To assess tumor uptake in-vivo, 111In-RP782 (~50 µCi) was administered iv in mice and tissue sampling was performed at 60 minutes post injection. As reference, tumor uptake of flurpiridaz F 18, a perfusion imaging agent, was measured. Additionally, 111In-RP782 imaging was also performed in these mice. Results Active MMP-2 and -9 activity levels in tumors were high in oncomice and HT-1080 xenograft mice (35±13 and 10±4, 28±3 and 19±4 pg/µg protein, n=4/each) compared to PC-12 xenograft mice (13±5 and 4±1 pg/µg protein, n=4). In-vivo tissue sampling showed that 111In-RP782 tumor uptake was 8.1±0.8 and 8.9±1.9% injected dose per gram tissue (%ID/g) in oncomice and HT-1080 xenograft mice (n=8-9), also high in comparison with PC-12 mice (3.4±0.5%ID/g, n=3). As reference, flurpiridaz F 18 tumor uptake was 2.9±0.2 and 2.2±0.5 %ID/g in oncomice and HT-1080 xenograft mice, much lower than that of 111In-RP782. Consistent with tumor sampling, imaging with 111In-RP782 detected tumors in oncomice and HT-1080 xenograft mice. Conclusions 111In-RP782 uptake in-vivo is in agreement with MMP activity in the tumor and it may have potential to be used for tumor imaging