New derivatives of vitamin B12 show preferential targeting of tumors.
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.
Waibel
Robert
R
Center for Radiopharmaceutical Science, Paul Scherrer Institute, Villigen PSI, Switzerland. robert.waibel@psi.ch
Treichler
Hansjörg
H
Schaefer
Niklaus G
NG
van Staveren
Dave R
DR
Mundwiler
Stefan
S
Kunze
Susanne
S
Küenzi
Martin
M
Alberto
Roger
R
Nüesch
Jakob
J
Knuth
Alexander
A
Moch
Holger
H
Schibli
Roger
R
Schubiger
Pius August
PA
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*
D000970:Antineoplastic Agents; D014155:Transcobalamins; D014805:Vitamin B 12