Synthesis and Preliminary Evaluation of a New 99mTc Labeled Substance P Analogue as a Potential Tumor Imaging Agent

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)-tyr^8-met(o)^11-sp] was synthesized and radiolabeled with 99mtc using ethylenediamine-n,n›-diacetic acid (edda)and tricine as coligands. common physicochemical 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 bearingnude 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 showed 44% protein binding to human serumalbumin. 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 4 h. 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.