Synthesis, Radiolabeling and Gastrin Releasing Peptide Receptor Binding Affinity of a Novel Bombesin Antagonist-Based Peptide, DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2
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Bombesin receptors are overexpressed in many kinds of human tumors. In particular,the gastrin releasing peptide receptor (GRPR) which is also called bombesin receptor subtype 2,has been identified in prostate cancer. In the present study, we developed a bombesin antagonistbased177Lu-labeled peptide, 177Lu-DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methylGly-His-Statine-Leu-NH2(DOTA-sBBNA). DOTA-sBBNA was prepared using a solid phase synthesismethod. It was labeled with 177Lu by a high radiolabeling yield (¤98%), and its Log P valuewas - 2.05. The radiolabeled peptide was highly stable in serum incubation at 37C for 48 hr. Acompetitive displacement of 125I-[Tyr4]-Bombesin on the PC-3 human prostate carcinoma cellsrevealed that the IC50 value of the peptide was 6.76 nM indicating a highly nanomolar bindingaffinity for GRPR. These results suggest that 177Lu-DOTA-sBBNA can be a potential candidatefor targeting prostate cancer, and further studies to evaluate its biological characteristics areneeded.
Abstract
Bombesin receptors are overexpressed in many kinds of human tumors. In particular,the gastrin releasing peptide receptor (GRPR) which is also called bombesin receptor subtype 2,has been identified in prostate cancer. In the present study, we developed a bombesin antagonistbased177Lu-labeled peptide, 177Lu-DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methylGly-His-Statine-Leu-NH2(DOTA-sBBNA). DOTA-sBBNA was prepared using a solid phase synthesismethod. It was labeled with 177Lu by a high radiolabeling yield (¤98%), and its Log P valuewas - 2.05. The radiolabeled peptide was highly stable in serum incubation at 37C for 48 hr. Acompetitive displacement of 125I-[Tyr4]-Bombesin on the PC-3 human prostate carcinoma cellsrevealed that the IC50 value of the peptide was 6.76 nM indicating a highly nanomolar bindingaffinity for GRPR. These results suggest that 177Lu-DOTA-sBBNA can be a potential candidatefor targeting prostate cancer, and further studies to evaluate its biological characteristics areneeded.
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