title: Synthesis and preliminary evaluation of a new (99m)tc labeled substance p analogue as a potential tumor imaging agent.
abstract: 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 (99m)Tc 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 (99m)Tc 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.
authors.affiliation: Department of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mozaffari
authors.affiliation: Nuclear Science Research School, Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran (AEOI), Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Erfani
authors.affiliation: Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Beiki
authors.affiliation: Nuclear Science Research School, Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran (AEOI), Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Johari Daha
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Kobarfard
authors.affiliation: Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Balalaie
authors.affiliation: Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Fallahi
keywords: 99mTc; HYNIC; NK1R; Substance P analogue; U373MG cells