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Pre-clinical study on tumor vasoactive intestinal peptide receptor scintigraphy
Xuejuan Wang1, Meiying Zhang, Zhi Yang
1Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing Cancer Hospital, Beijing 100036, China.
Objective:
To develop a tumor imaging agent for vasoactive intestinal peptide (VPAC) receptor and evaluate its biological activity and pharmacokinetics of radiolabeled peptide.
Methods:
VIP(28) was modified at the carboxyl terminal by the addition of His-tag which was the chelating site of (99m)Tc(I) and the general purification tag for immobilized metal ion affinity chromatography. Biological activity of the modified VIP(28) analogue MY34 was examined in vitro by radiological cell-binding assay, rabbit internal anal sphincter (IAS) smooth muscle relaxing assay and immunocytochemical stain. The pharmacokinetics of this labeled peptide was examined in C57 mice.
Results:
MY34 could relax the IAS smooth muscle and bind VPAC receptors on tumor cell membranes. (99m)Tc- MY34, with a yield of about 90%, was stable enough for practical use. Both MY34 and VIP(28) could inhibit the binding between the labeled peptide and VPAC receptor. The pharmacokinetics of [(99m)Tc(H(2)O)(3)(CO)(3)]-MY34 was studied in mice conformed well with the two-compartment model (Wi = 1/C(2)), with a t(1)/(2alpha) of 16.35 min and a t(1)/(2beta) of 1013.56 min.
Conclusion:
MY34 possesses physiological activities and specific receptor binding characteristics similar to those of natural VIP(28).
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