title: Preparation and biodistribution of copper-67-labeled porphyrins and porphyrin-A6H immunoconjugates.
abstract: The synthetic porphyrins, N-benzyl-5,10,15,20-tetrakis (4-carboxyphenyl) porphine (N-bzHTCPP) and N-4-nitrobenzyl-5-(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl) porphine (N-bzHCS3P), represent excellent radiocopper chelating agents that may find utility in antibody-mediated diagnosis and/or therapy. N-bzHCS3P was conjugated to an anti-renal cell carcinoma (RCC) antibody, A6H, and labeled with copper-67. 67CuCS3P-A6H was studied for its biodistribution in human RCC xenograft-bearing nude mice, along with the radiolabeled free porphyrins. The porphyrins resulted in tumor:blood ratios in the range of 3 to 4 after 48 h. The radiolabeled antibody achieved a tumor:blood ratio of over 16 after 45 h, indicating accumulation at the desired site. However, unwanted localization also occurred in the liver and spleen, which will have to be rectified before realizing the full potential of this approach.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Bhalgat
authors.forename: J C
authors.initials: JC
authors.lastname: Roberts
authors.forename: J A
authors.initials: JA
authors.lastname: Mercer-Smith
authors.forename: B D
authors.initials: BD
authors.lastname: Knotts
authors.forename: R L
authors.initials: RL
authors.lastname: Vessella
authors.forename: D K
authors.initials: DK
authors.lastname: Lavallee
mesh_terms: D000818:Animals; D000906:Antibodies; D001692:Biological Transport; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism*; D002614:Chelating Agents; D003301:Copper Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D007553:Isotope Labeling; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011166:Porphyrins / Q000493:pharmacokinetics*; D016719:Radioimmunodetection; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D002614:Chelating Agents; D003301:Copper Radioisotopes; D011166:Porphyrins; C106110:N-benzyl-5,10,15,20-tetrakis(4-carboxyphenyl)porphine; C062668:N-4-nitrobenzyl-5-(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl)porphine