Investigation of a Vitamin B 12 Conjugate as a PET Imaging Probe

• Published in: ChemMedChem 2014-06, Vol.9 (6), p.1244-1251
• Main Authors: Ikotun, Oluwatayo F., Marquez, Bernadette V., Fazen, Christopher H., Kahkoska, Anna R., Doyle, Robert P., Lapi, Suzanne E.
• Format: Article
• Language: English
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201400048

Nutrient demand is a fundamental characteristic of rapidly proliferating cells. Vitamin B 12 is vital for cell proliferation; thus neoplastic cells have an increased demand for this essential nutrient. In this study we exploited the vitamin B 12 uptake pathway to probe the nutritional demand of proliferating cells with a radiolabeled B 12 derivative in various preclinical tumor models. We describe the synthesis and biological evaluations of copper‐64‐labeled B 12 –ethylenediamine–benzyl‐1,4,7‐triazacyclononane‐ N , N ′, N ′′‐triacetic acid (B 12 ‐en‐Bn‐NOTA‐ 64 Cu), the first example of a B 12 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 B 12 resulted in a 95 % decrease in tumor accumulation, indicating the specificity of this radiopharmaceutical for B 12 endocytotic transport proteins. These results show that a vitamin B 12 PET radiopharmaceutical has potential utility for non‐invasive imaging of enhanced nutrient demand in proliferating cells.