PET/CT and near-infrared fluorescence imaging of tumors using a cRGD-based multimodal imaging agent

Abstract

Introduction: Hybrid tracers, allowing both preoperative nuclear and intraoperative near infrared fluorescence (NIRF) imaging, can aid in accurate preoperative surgical planning and intraoperative real-time detection of the tumor. cRGD peptide targets integrins associated with angiogenesis and has been used successfully for both nuclear and fluorescent imaging. This study evaluates the hybrid tracer cRGD-[89Zr]Zr-DFO-ZW800F for positron emission tomography (PET) and NIRF imaging in a cancer mouse model. Methods: Ten nmol cRGD-Zr-DFO-ZW800F was injected in mice (n = 7) bearing orthotopic colorectal tumors (HT29-luc2). NIRF imaging was performed using the Pearl Imager, bioluminescent signals were measured with the IVIS Spectrum. Second, 10 nmol cRGD-[89Zr]Zr-DFO-ZW800F(3 MBq) was administered to mice (n = 8) and a nuclear imaging was performed with the NanoPET/CT Mediso at 1 h, 4 h and 24 h post injection. The percentage of the injected dose per gram in each organ/tissue(%ID/g) at 4 h and 24 h post injection was measured ex-vivo with the gammacounter. Results: Sufficient fluorescent signals were measured in the tumors of the mice injected with cRGD-Zr-DFO-ZW800F (emission peak ∼800 nm). The fluorescent signal of cRGD-[89Zr]Zr-DFO-ZW800F remained stable after labelling with zirconium-89 and PET-CT at 4 h allowed clear visualization of colorectal tumors. Biodistribution at 4 h showed the highest uptake of the tracer in kidneys (16.8 ± 8.6 % ID/g) and sufficient uptake in the tumor (0.9 ± 0.1 % ID/g). At 24 h the uptake in the tumor was still sufficient (0.8 ± 0.2 % ID/g for PET imaging). Conclusion: This study shows the feasibility of PET and fluorescence imaging of tumors with a single injection of cRGD-[89Zr]Zr-DFO-ZW800F, allowing preoperative surgical planning followed by intra-operative real-time imaging.