Selective Targeting of Melanoma Tumor by F-18 Fluorobenzamide (F-18 FBENZ): Tracer Kinetics and Preclinical Assessment in Mouse Model using MicroPET.

1173 Objectives The objective of this study is to assess the selectivity and specificity of F-18 Fluorobenzamide (F-18 FBENZ) to target melanotic melanoma using a tumor xenograft mouse model. Methods F-18 FBENZ was synthesized as described earlier (1). Melanoma tumor xenograft (B16F1) was established in the right flank of five C57BL/6 mice. LNCaP (prostate) and PC12 (pheochromocytoma) tumor xenografts were established in the right flank of athymic nu/nu mice. F-18 FBENZ was injected via the tail vein and whole body microPET scans were acquired for two hours post injection for the melanoma group and from 30-50 min post injection for the LNCaP and PC12 groups. The data was reconstructed using FBP (filtered back projection) with attenuation correction and analyzed using ASIPro (Siemens) software. Regions of interest (ROI) were drawn on select organs using a summed image of the two-hour acquisition and TACs (time activity curves) were generated from the reconstructed list-mode data. The ROI data was subsequently normalized to 100 uCi injected dose to enable inter-group comparison for the uptake and kinetics assessment. Results F-18 FBENZ accumulation in the B16F1 tumor was rapid and increased steadily for the first 60 min post injection. The initial uptake in normal tissues was low and radioactivity washed out from normal tissues over time, which combined with the high F-18 accumulation in the melanoma tumors effectively lead to higher tumor to normal tissue ratios when compared to the LNCaP and PC12 xenografts. The tumor to tissue ratios for the liver, muscle, and brain were 0.55 ± 0.01, 2.48 ± 0.01, and 1.22 ± 0.02 for the LNCaP group, 0.29 ± 0.00, 2.48 ± 0.03, and 1.05 ± 0.02 for the PC12 group, and 2.92 ± 0.03, 12.20 ± 0.04, and 7.20 ± 0.03 for the melanoma tumor. Pre-injection of non-radioactive FBENZ did not alter the F-18 accumulation in the tumor; indicating a high-capacity, non-saturable uptake pathway for this radiotracer. High F-18 accumulation in the melanoma tumors along with a low normal tissues uptake helped clearly delineate tumors as early as 10 min post injection. In contrast, the low F-18 accumulation in tumors from the LNCaP and PC 12 groups (non-specific tumors) led to significantly less conspicuous tumor visualizations to the point where delineation of these tumors was rather difficult. Standard uptake values (SUVs) for the B16F1, PC12, and LNCaP tumors were 4.11, 0.28, and 0.16 with a 13-fold higher selectivity for F-18 FBENZ in the melanoma tumors This selectivity is further evident from the image sets across the entire length of scan acquisition time. Urinary excretion was observed to be the primary clearance method. Conclusions Uptake and distribution kinetics of F-18 FBENZ in melanoma tumors was rapid and high, resulting in clear delineation of tumor as early as 10 min post injection. After an initial distribution of radioactivity, the F-18 rapidly cleared from normal tissues, thus providing high tumor to background ratios. F-18 uptake in the non-melanoma tumors was significantly lower than the melanoma tumors, demonstrating high specificity of F-18 FBENZ towards melanoma tumors. These preclinical studies support the potential of F-18 FBENZ as useful probe to selectively target melanoma.