title: Targeting gastrin-releasing peptide receptors of prostate cancer cells for photodynamic therapy with a phthalocyanine-bombesin conjugate.
abstract: Sulfonated aluminum phthalocyanines (AlPcS) are potent photosensitizers for the photodynamic therapy (PDT) of cancer. In this study we evaluate the possibility to improve the efficacy of AlPcS-PDT for prostate cancer by targeting tetrasulfonated aluminum phthalocyanines (AlPcS(4)) to the gastrin-releasing peptide receptor (GRPR) through coupling to bombesin. A mono-carbohexyl derivative of AlPcS(4) is attached to 8-Aoc-bombesin(7-14)NH(2) via an amide bridge to yield a bombesin-AlPcS(4) conjugate linked by a C-14 spacer chain. The conjugate is characterized by mass spectroscopy and shown to bind to the GRPR with a relative binding affinity (RBA) of 2.3, taking bombesin (RBA=100) as unity. The in vitro photodynamic efficacy of the conjugate against PC-3 human prostate cancer cells is improved by a factor 2.5 over the non-conjugated mono-carbohexyl derivative of AlPcS(4).
authors.affiliation: Department of Nuclear Medicine & Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Que., Canada J1H 5N4.
authors.forename: Céléna
authors.initials: C
authors.lastname: Dubuc
authors.forename: Réjean
authors.initials: R
authors.lastname: Langlois
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.forename: Nicole
authors.initials: N
authors.lastname: Cauchon
authors.forename: Klaus
authors.initials: K
authors.lastname: Klarskov
authors.forename: Paul
authors.initials: P
authors.lastname: Tone
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
mesh_terms: D001665:Binding Sites; D001839:Bombesin / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D013058:Mass Spectrometry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018004:Receptors, Bombesin / Q000378:metabolism*
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D018004:Receptors, Bombesin; C048577:aluminum tetrasulfophthalocyanine; D001839:Bombesin