1. Investigation of a vitamin B12 conjugate as a PET imaging probe.
- Author
-
Ikotun OF, Marquez BV, Fazen CH, Kahkoska AR, Doyle RP, and Lapi SE
- Subjects
- Animals, Cell Line, Tumor, Coordination Complexes pharmacokinetics, Copper Radioisotopes chemistry, HCT116 Cells, Heterocyclic Compounds chemistry, Heterocyclic Compounds, 1-Ring, Humans, Melanoma, Experimental diagnosis, Melanoma, Experimental diagnostic imaging, Mice, Mice, Nude, Positron-Emission Tomography, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, Tomography, X-Ray Computed, Transplantation, Heterologous, Transplantation, Homologous, Coordination Complexes chemistry, Radiopharmaceuticals chemistry, Vitamin B 12 chemistry
- 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., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2014
- Full Text
- View/download PDF