title: Investigation of a vitamin B12 conjugate as a PET imaging probe.
abstract: Nutrient demand is a fundamental characteristic of rapidly proliferating cells. Vitamin B12 is vital for cell proliferation; thus neoplastic cells have an increased demand for this essential nutrient. In this study we exploited the vitamin B12 uptake pathway to probe the nutritional demand of proliferating cells with a radiolabeled B12 derivative in various preclinical tumor models. We describe the synthesis and biological evaluations of copper-64-labeled B12 -ethylenediamine-benzyl-1,4,7-triazacyclononane-N,N',N''-triacetic acid (B12 -en-Bn-NOTA-(64) Cu), the first example of a B12 derivative for positron emission tomography (PET) imaging. Small-animal imaging and pharmacological evaluation show high tumor uptake ranging from 2.20 to 4.84% ID g(-1) at 6 h post-administration. Competition studies with excess native B12 resulted in a 95% decrease in tumor accumulation, indicating the specificity of this radiopharmaceutical for B12 endocytotic transport proteins. These results show that a vitamin B12 PET radiopharmaceutical has potential utility for non-invasive imaging of enhanced nutrient demand in proliferating cells.
authors.affiliation: Department of Radiological Sciences, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus Box 8225, St. Louis, MO 63110 (USA), Fax: (+1) 315-362-4696.
authors.forename: Oluwatayo F
authors.initials: OF
authors.lastname: Ikotun
authors.forename: Bernadette V
authors.initials: BV
authors.lastname: Marquez
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Fazen
authors.forename: Anna R
authors.initials: AR
authors.lastname: Kahkoska
authors.forename: Robert P
authors.initials: RP
authors.lastname: Doyle
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Lapi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000493:pharmacokinetics; D003301:Copper Radioisotopes / Q000737:chemistry; D045325:HCT116 Cells; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008546:Melanoma, Experimental / Q000175:diagnosis / Q000000981:diagnostic imaging; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014805:Vitamin B 12 / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D014805:Vitamin B 12
keywords: CD320; cobalamin; positron emission tomography; radiochemistry; vitamins