Investigation of a vitamin B12 conjugate as a PET imaging probe

Oluwatayo F. Ikotun, Bernadette V. Marquez, Christopher H. Fazen, Anna R. Kahkoska, Robert Patrick Doyle, Suzanne E. Lapi

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 (B 12-en-Bn-NOTA-64Cu), 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. Co-opting cobalamin: Vitamin B12 is an essential nutrient for all proliferating cells. Rapid proliferation is a common hallmark of cancer; consequently, neoplastic cells have an increased demand for vitamin B12. We exploited the vitamin B12 uptake pathway to non-invasively probe the nutrient demand of cancer cells. The synthesis, characterization, and tumor-homing properties of a vitamin B12 PET radiotracer are described.

Original languageEnglish (US)
Pages (from-to)1244-1251
Number of pages8
JournalChemMedChem
Volume9
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Positron emission tomography
Vitamin B 12
Positron-Emission Tomography
Imaging techniques
Nutrients
Tumors
Food
Neoplasms
ethylenediamine
Radiopharmaceuticals
Derivatives
Cell proliferation
Copper
Carrier Proteins
Animals
Cells
Cell Proliferation
Pharmacology
Acids

Keywords

  • CD320
  • cobalamin
  • positron emission tomography
  • radiochemistry
  • vitamins

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine
  • Medicine(all)

Cite this

Ikotun, O. F., Marquez, B. V., Fazen, C. H., Kahkoska, A. R., Doyle, R. P., & Lapi, S. E. (2014). Investigation of a vitamin B12 conjugate as a PET imaging probe. ChemMedChem, 9(6), 1244-1251. https://doi.org/10.1002/cmdc.201400048

Investigation of a vitamin B12 conjugate as a PET imaging probe. / Ikotun, Oluwatayo F.; Marquez, Bernadette V.; Fazen, Christopher H.; Kahkoska, Anna R.; Doyle, Robert Patrick; Lapi, Suzanne E.

In: ChemMedChem, Vol. 9, No. 6, 2014, p. 1244-1251.

Research output: Contribution to journalArticle

Ikotun, OF, Marquez, BV, Fazen, CH, Kahkoska, AR, Doyle, RP & Lapi, SE 2014, 'Investigation of a vitamin B12 conjugate as a PET imaging probe', ChemMedChem, vol. 9, no. 6, pp. 1244-1251. https://doi.org/10.1002/cmdc.201400048
Ikotun, Oluwatayo F. ; Marquez, Bernadette V. ; Fazen, Christopher H. ; Kahkoska, Anna R. ; Doyle, Robert Patrick ; Lapi, Suzanne E. / Investigation of a vitamin B12 conjugate as a PET imaging probe. In: ChemMedChem. 2014 ; Vol. 9, No. 6. pp. 1244-1251.
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