99mTc-SAMA-GGG-Ahx-BBN for GRP receptor targeting

1527 Objectives Many investigations have been conducted with diagnostic radiotracers guided to prostate cancer. Bombesin (BBN) conjugated radioligands have been among them due the overexpression of BBN receptors in the prostate tumor cells, however results are still debated. The aim of this study was the uptake of 99mTc-MAG3-Ahx-BBN (7-14)NH2 in healthy animals and in- vitro binding studies in tumor cells. Methods SAMA-GGG-Ahx-BBN was labeled with technetium-99m using sodium tartrate dissolved in labeling buffer (ammonium bicarbonate, ammonium acetate, ammonium hydroxide), along with stannous chloride solution. Reaction was induced by heating at 100 oC for 20 min. Radiochemical evaluation was performed by ITLC and was confirmed by HPLC analysis. 99mTc-MAG3-Ahx-BBN was injected in healthy swiss mice (0.1 mL)/18.5 MBq) and biodistribution was evaluated at 5, 30, 90 and 240 min post-injection. Binding studies (saturation and internalization) were done with human prostate tumor cells PC-3. Results 99mTc-MAG3-Ahx-BBN radiochemical purity was 96.3± 1.2%, with a retention time of 13.4 min. Fast blood clearance and a hepatobiliary excretion were observed as well as substantial uptake in pancreas (6.58% ID/g at 5 min pi), which expresses BBN receptors. Receptor saturation studies in PC-3 cells showed Kd = 284 pM and Bmax = 154 pM. At 37oC more than 75% was internalized within the first 30 min and remained constant for 2 hours. Conclusions 99mTc-MAG3-Ahx-BBN demonstrated high affinity for BBN receptors. The promising results merit future investigation in tumor-bearing animals, including comparison with other radiotracers for prostate cancer