Novel 18F-labeled aliphatic probe for melanoma imaging

Objectives Radiofluorinated benzamide and nicotinamide analogs have been demonstrated to be promising probes for melanoma PET imaging. The aim of this study was to explore the feasibility of using aliphatic compounds for development of new generation melanoma PET probes.

Methods An aliphatic N,N-diethylethylenediamine precursor was directly labeled with a radiofluorination synthon, p-nitrophenyl 18F-fluoropropionate (18F-NFP), to produce a probe18F-FPDA. MicroPET imaging using 18F-FPDA was performed in melanoma murine models. The specificity of 18F-FPDA to melanoma was evaluated in vivo by biodistribution studies and micro-positron emission tomography (microPET) imaging in C57BL/6 mice bearing B16F10 murine melanoma tumors.

Results Starting with precursor 18F-NFP, the total reaction time for 18F-FPDA, including final high-performance liquid chromatography purification, is about 30 min, with decay-corrected radiochemical yield of 79.8%. The B16F10 cell study demonstrated by significant different uptake in tyrosine-treated and untreated B16F10 cells in vitro. In pigmented-enriched B16F10 xenografts, tumor uptakes reached 5.41 %ID/g at 0.5 h post injection and the sustained tumor uptake at 2 h post injection was 3.05 %ID/g, while in the non-pigmented U87MG and PC3 models, the tumor uptakes were only the background levels. Due to the high selectivity between targeted and non-targeted organs for 18F-FPDA, the animal PET imaging study yielded a high tumor-to-muscle ratio of approximately 8:1 at 1 h and 14:1 at 2 h post injection.

Conclusions The new tracer 18F-FPDA was synthesized with high yield via 18F-NFP and the tracer exhibited high B16F10 tumor-targeting efficacy, and favorable in vivo pharmacokinetics. Further testing and clinical translation of 18F-FPDA for noninvasive clinical evaluation of suspected malignant melanoma are warranted