title: Synthesis of Poly[APMA]-DOTA-64Cu conjugates for interventional radionuclide therapy of prostate cancer: assessment of intratumoral retention by micro-positron emission tomography.
abstract: To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropyl)methacrylamide] [poly(APMA)] polymers were synthesized by free radical precipitation polymerization in acetone-dimethylsulfoxide using N,N'-azobis(isobutyronitrile) as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (M(n) = 2.40 x 10(4), M(w)/M(n) = 1.87). Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with (64)Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-(64)Cu conjugates within the tumor tissues was demonstrated by micro-positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-(64)Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, MI, USA.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Yuan
authors.forename: Yezi
authors.initials: Y
authors.lastname: You
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.forename: David
authors.initials: D
authors.lastname: Oupicky
authors.forename: Fangyu
authors.initials: F
authors.lastname: Peng
mesh_terms: D000180:Acrylic Resins / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000818:Animals; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009570:Nitriles / Q000737:chemistry; D009942:Organometallic Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D012542:Scattering, Radiation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000180:Acrylic Resins; D006573:Heterocyclic Compounds, 1-Ring; D009570:Nitriles; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C524817:poly(N-(3-aminopropyl)methacrylamide)-DOTA-64Cu conjugate; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C004526:azobis(isobutyronitrile)