Tehran University of Medical Sciences
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Davood Beiki

Synthesis and preliminary evaluation of a new 99mTc labeled substance P analogue as a potential tumor imaging agent

Authors: Mozafari S, Erfani M, Beiki D, Johari Daha F, Kobarfard F, Balalaie S, Fallahi B,
Keywords: NK1R; Substance P analogue; 99mTc; HYNIC; U373MG cells
Iran J Pharm Res, Vol.14, No.1, 2015,Page:97-110

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors. [6-hydrazinopyridine-3-carboxylic acid(HYNIC)-Tyr8-Met(O)11-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemichal properties of radioconjugate were studied and in vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In vivo biodistribution in normal and tumor bearing nude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with 99mTc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in vitro in the presence of human serum and showed44% protein binding to human serum albumin. In vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated.

Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.