title: Synthesis and characterization of αvβ₃-targeting peptidomimetic chelate conjugates for PET and SPECT imaging.
abstract: There is growing interest in small peptidomimetic α(v)β(3) integrin antagonists that are readily synthesized and characterized and can be easily handled using physiological conditions. Peptidomimetic 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-β-alanine (IAC) was successfully conjugated to 1-(1-carboxy-3-carbo-t-butoxypropyl)-4,7-(carbo-tert-butoxymethyl)-1,4,7-triazacyclononane (NODA-GA(tBu)(3)) and 1-(1-carboxy-3-carbotertbutoxymethyl)-1,4,7,10-tetraazacyclododecane (DOTA-GA(tBu)(4)) and radiolabeled with (111)In, (67)Ga and (203)Pb. Results of a radioimmunoassay demonstrated binding to purified α(v)β(3) integrin when 1-4equiv of integrin were added to the reaction. Based on this promising result, investigations are moving forward to evaluate the NODA-GA-IAC and DOTA-GA-IAC conjugates for targeting tumor associated angiogenesis and α(v)β(3) integrin positive tumors to define their PET and SPECT imaging qualities as well as their potential for delivery of therapeutic radionuclides.
authors.affiliation: Radioimmune & Inorganic Chemistry Section, ROB, NCI, NIH, 10 Center Drive, MSC-1002, Rm B3B69, Bethesda, MD 20892-1002, USA.
authors.forename: Young-Seung
authors.initials: YS
authors.lastname: Kim
authors.forename: Kido
authors.initials: K
authors.lastname: Nwe
authors.forename: Diane E
authors.initials: DE
authors.lastname: Milenic
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Stanley
authors.initials: S
authors.lastname: Satz
authors.forename: Kwamena E
authors.initials: KE
authors.lastname: Baidoo
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D007856:Lead Radioisotopes / Q000737:chemistry / Q000378:metabolism; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011863:Radioimmunoassay; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D039302:Integrin alphaVbeta3; D007856:Lead Radioisotopes; D057786:Peptidomimetics; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid