Design, synthesis and preliminary in vitro and in vivo evaluation of 4-[18F]fluoro-N-(2-diethylaminoethyl)benzamide ([18F]-DAFBA): A novel potential PET probe to image melanoma tumors

In order to develop a PET radiopharmaceutical to image malignant melanoma, we synthesized N -(2-diethylaminoethyl)-4-[ 18 F]fluorobenzamide ([ 18 F]-DAFBA). In vitro studies show a high uptake of [ 18 F]-DAFBA by the B16F1 melanoma cells. No significant binding was seen for DAFBA to the sigma-1 and sigma-2 receptors in vitro . The i n vivo biodistribution studies performed in normal ICR mice showed a low uptake in the normal tissues followed by further elimination of radioactivity from these tissues with time. The biodistribution studies performed in C57 mice bearing melanoma tumor xenograft showed a rapid uptake of radioactivity in the tumor that reached a plateau within 30 min post injection. The F-18 uptake in the tumor was 7.00±2.76, 6.57±1.66, and 5.80±0.98 %ID/g at 60, 120, and 180 min, respectively. A steady uptake of radioactivity in the tumor and low uptake in normal tissues resulted in high tumor to normal tissue ratios. For example, at 180 min post-injection, the tumor to tissue ratios were 14.90±6.47, 21.90±4.68, 32.91±6.11, 36.73±5.61, and 6.33±1.9, for the spleen, lungs, muscle, blood, and liver, respectively. The radioactivity rapidly cleared from the blood pool and it decrease from 0.58±0.18 %ID/g at 60 min to 0.13±0.03 %ID/g at 180 min. The F-18 uptake in the bones at 60, 120, and 180 min was 0.91±0.27, 0.57±0.32, and 0.17±0.05 %ID/g, respectively. This low uptake in the bones reflects its in vivo resistance towards de-fluorination. A low residual activity in normal tissues and a high tumor uptake signifies a superior imaging potential of this compound. Owing to these positive traits, [ 18 F]-DAFBA could help delineate tumor and its metastases when used for imaging application. Further in vivo studies are underway to assess potential of [ 18 F]-DAFBA as a promising PET imaging probe.