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New Derivatives of Vitamin B12 Show Preferential Targeting of Tumors

¹ Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen PSI, Switzerland; ² Ringgackerstrasse 1, Känerkinden, Switzerland; ³ Clinic of Medical Oncology, University Hospital of Zurich; ⁴ Department of Inorganic Chemistry, University of Zurich; ⁵ Institute of Surgical Pathology, Department Pathology, University Hospital of Zurich; and ⁶ Department of Chemistry and Applied Biosciences of the Eidgenössische Technische Hochschule Zürich, Zurich, Switzerland; and ⁷ Solidago AG, Bern, Switzerland

Requests for reprints: Robert Waibel, Center for Radiopharmaceutical Science, Paul Scherrer Institute, CH-5232 Villigen PSI, Switzerland. Phone: 56-310-2826; Fax: 56-310-2849; E-mail: robert.waibel{at}psi.ch.

Key Words: vitamin B12 • targeting • cancer • transcobalamin

Rapidly growing cells show an increased demand for nutrients and vitamins. The objective of our work is to exploit the supply route of vitamin B12 to deliver new derivatives of this vital vitamin to hyperproliferative cells. To date, radiolabeled (⁵⁷Co and ¹¹¹In) vitamin B12 derivatives showed labeling of tumor tissue but also undesired high accumulation of radioactivity in normal tissue. By abolishing the interaction of a tailored vitamin B12 derivative to its transport protein transcobalamin II and therefore interrupting transcobalamin II receptor and megalin mediated uptake in normal tissue, preferential accumulation of a radiolabeled vitamin in cancer tissue could be accomplished. We identified transcobalamin I on tumors as a possible new receptor for this preferential accumulation of vitamin-mediated targeting. The low systemic distribution of radioactivity and the high tumor to blood ratio opens the possibility of a more successful clinical application of vitamin B12 for imaging or therapy. [Cancer Res 2008;68(8):2904–11]