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Rivista di Medicina Nucleare e Imaging Molecolare

A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the Society of Radiopharmaceutical Sciences and to the International Research Group of Immunoscintigraphy
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The Quarterly Journal of Nuclear Medicine 2001 June;45(2):160-6

lingua: Inglese

Modern trends in radioimmunotherapy of cancer: pretargeting strategies for the treatment of ovarian cancer

McQuarrie S. A., Xiao Z., Miller G. G. *, Mercer J. R., Suresh M. R.

From the Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta, Edmonton
*Noujaim Institute for Phar­ma­ceu­ti­cal Oncology Research, University of Alberta, Edmonton, Canada


A ­review of pub­lished ­data on ­some of the prob­lems asso­ciat­ed in treat­ing can­cer ­using radio­im­mu­no­ther­a­py is pre­sent­ed. Potential improve­ments for ­this ­type of ther­a­py ­using pretar­get­ing strat­e­gies are dis­cussed and pre­lim­i­nary ­results on a nov­el mul­ti­step reg­i­men to ­treat ­human ovar­ian can­cer are pre­sent­ed. A pre­tar­get­ing strat­e­gy ­using a bio­tin­y­lat­ed, ­anti-CA125 mono­clo­nal anti­body (MAb) to ­attract bio­tin­y­lat­ed ­long-cir­cu­lat­ing lipo­somes to the sur­face of CA125-express­ing ovar­ian can­cer ­cells, was ­employed. Confocal ­laser scan­ning micros­co­py and flu­o­res­cent ­labels ­were ­used to estab­lish the bio­dis­trib­u­tion pat­terns in NIH:­OVCAR-3 (CA-125 pos­i­tive) and SK-OV-3 (CA-125 neg­a­tive) ­human ovar­ian can­cer ­cells. Shedding kinet­ics of the pretar­get­ed ­stage ­were meas­ured ­using 125I ­labeled MAbs. No sig­nif­i­cant inter­nal­iza­tion of the MAb ­used in the pre­tar­get­ing ­step was ­observed by 4 hrs. The anti­body was grad­u­al­ly inter­nal­ized start­ing at 6 hrs, and ­most of the ­labelled MAb was detect­ed in cyto­plasm by 24 hrs. Shedding and exo­cy­to­sis of the anti­gen-MAb com­plex was not sig­nif­i­cant for up to 6-­hours fol­low­ing admin­is­tra­tion of the iod­i­nat­ed MAb. Biotinylated lipo­somes ­were ­shown to spe­cif­i­cal­ly tar­get the bio­tin­y­lat­ed MAb/strep­tav­i­din com­plex on the ­cell sur­face. We ­have dem­on­strat­ed ­that by a ­three-­step pre­tar­get­ing ­approach, bio­tin­y­lat­ed lipo­somes can be spe­cif­i­cal­ly deliv­ered to ­cells pre­tar­get­ed ­with bio­tin­y­lat­ed MAb/SAv com­plex. The ­slow inter­nal­iza­tion and shed­ding prop­er­ties of the two MAbs are ­ideal for mul­ti­step pre­tar­get­ing meth­ods. A suc­cess­ful mul­ti­step link­age was estab­lished ­with the bio­tin­y­lat­ed MAb B27.1, strep­tav­i­din and bio­tin­y­lat­ed lipo­somes to ­OVCAR-3 ­cells, but not to SK-OV-3 ­cells.

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