title: New derivatives of vitamin B12 show preferential targeting of tumors.
abstract: 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 ((57)Co and (111)In) 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.
authors.affiliation: Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen PSI, Switzerland. robert.waibel@psi.ch
authors.forename: Robert
authors.initials: R
authors.lastname: Waibel
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Treichler
authors.forename: Niklaus G
authors.initials: NG
authors.lastname: Schaefer
authors.forename: Dave R
authors.initials: DR
authors.lastname: van Staveren
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundwiler
authors.forename: Susanne
authors.initials: S
authors.lastname: Kunze
authors.forename: Martin
authors.initials: M
authors.lastname: Küenzi
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
authors.forename: Jakob
authors.initials: J
authors.lastname: Nüesch
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Pius August
authors.initials: PA
authors.lastname: Schubiger
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D002277:Carcinoma; D045744:Cell Line, Tumor; D006801:Humans; D007680:Kidney Neoplasms; D008545:Melanoma; D014155:Transcobalamins / Q000187:drug effects / Q000378:metabolism; D001749:Urinary Bladder Neoplasms; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014155:Transcobalamins; D014805:Vitamin B 12