RADIOPHARMACOLOGY 

The Quarterly Journal of Nuclear Medicine 2001 June;45(2):201-6

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Radiolabeled bivalent haptens for tumor immunodetection and radioimmunotherapy

Gruaz-Guyon A. *, Janevik-Ivanovska E. *, Raguin O. *, De Labriolle-Vaylet C. *°, Barbet J. **

From the *INSERM U.339, Faculté de Médecine et Hôpital Saint-Antoine, Paris °Service de Médecine Nucléaire, Hôpital Saint-Antoine, Paris **UPRES 3290, Faculté de Médecine, Université de la Méditerranée, Marseille, France

The pre­tar­geting tech­nique ­referred to as the ­Affinity Enhance­ment ­System (AES) ­uses bispe­cific anti­bodies and radio­lab­eled biva­lent hap­tens ­that ­bind coop­er­a­tively to ­target ­cells in ­vivo. Experi­mental and clin­ical ­data dem­on­strate ­that ­DTPA biva­lent hap­tens can ­deliver ­large radi­a­tion ­doses to ­tumor ­cells ­with ­high ­tumor to ­normal ­tissue con­trast ­ratios and ­long ­activity res­i­dence ­time in ­tumors. Pre­lim­i­nary clin­ical ­results of radio­im­mu­no­therapy of medul­lary thy­roid car­ci­nomas and ­lung can­cers ­look prom­ising. ­Very encour­aging ­results in bio­dis­trib­u­tion and radio­im­mu­no­therapy experi­ments in ani­mals ­have ­been ­obtained ­with new hap­tens ­bearing two his­ta­mine-hem­i­suc­ci­nate suit­able for 131I, 99mTc and 188Re ­labeling. Tar­geting iso­topes to ­double ­antigen pos­i­tive ­tumor ­cells pro­vides a ­binding enhance­ment ­that ­increases spec­i­ficity for ­tumor ­cells as com­pared to ­single ­antigen tar­geting on ­normal ­cells. ­This ­approach may be ben­e­fi­cial for tar­geting iso­topes to B ­type ­acute lym­pho­blastic leu­kemia and Bur­kitt lym­phoma, as ­well as ­others ­tumors co-­expressing two ­markers of low spec­i­ficity, and ­might ­increase ­tumor irra­di­a­tion ­with min­imal irra­di­a­tion of ­normal ­cells.