Synthesis and preliminary evaluation of a novel tumor imaging agent [18F]-[R8,15,21,L17]-VIP

Abstract

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Objectives: Radiolabeled VIP has showed its potential as tumor imaging agent. However, proteolytic degradation of VIP in vivo limits their clinical application. In this study, the structure of VIP was modified to get a noval VIP analogue radio-labeled with 18F,which would be developed as a tumor imaging agent with longer half life in vivo.

Methods: [R8,15,21,L17]-VIP was synthesized and its binding activity with rat lung extraction was evaluated. [18F]- [R8,15,21,L17]-VIP was obtained by conjugation of the prosthetic group [18F]SFB with peptide. The reaction conditions for the synthesis of [18F]SFB and radiolabeling of peptide were optimized. The stability of the product in vitro was tested.

Results: [R8,15,21,L17]-VIP has a high binding affinity with membrane protein extracted from rat lung(IC50=7.83nM).The radiochemical yield of [18F]SFB reached 65.3%±12.5% with more than 99% radiochemical purity(decay corrected). The conjugation efficiency of peptide with [18F]SFB was about 39.3-49.7% with average of 44.9%±4%(n=5). The effective specific radioactivity and radiochemical purity of the [18F]-peptide could reach 230GBq/µmol(EOS) and >99% ,respectively after purification by a RP-HPLC procedure. No degradation was founded after 4h incubation at 37 degree centigrade in HSA.

Conclusions: [18F]- [R8,15,21,L17]-VIP was synthesized successfully and would be a potential PET imaging agent for VIP receptors over-expressed tumor.

Research Support (if any): This work was supported by key project of knowledge innovation program of Chinese Academy of Sciences, Contract No. KJCX-SW-08, and supported by the National Nature Science Foundation No.30371634.