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The Quarterly Journal of Nuclear Medicine 2000 September;44(3):208-23


lingua: Inglese

Gene transfer strategies for improving radiolabeled peptide imaging and therapy

Rogers B. E., Zinn K. R., Buchsbaum D. J.

From the Departments of Radiation Oncology and *Radiology University of Alabama at Birmingham, Birmingham, AL, USA


Utilization of molec­u­lar biol­o­gy tech­niques ­offers attrac­tive ­options in nucle­ar med­i­cine for improv­ing can­cer imag­ing and ther­a­py ­with radio­lab­eled pep­tides. Two of ­these ­options ­include util­iza­tion of ­phage-pan­ning to iden­ti­fy nov­el ­tumor-spe­cif­ic pep­tides or sin­gle ­chain anti­bod­ies and ­gene trans­fer tech­niques to ­increase the num­ber of anti­gen/recep­tor ­sites ­expressed on malig­nant ­cells. Our ­group has ­focused on the lat­ter ­approach for improv­ing radio­lab­eled pep­tide imag­ing and ther­a­py. The ­most wide­ly ­used ­gene trans­fer vec­tors in clin­i­cal ­gene ther­a­py ­trials ­include ret­ro­vi­rus, cat­ion­ic lip­ids, and aden­o­vi­rus. We ­have uti­lized aden­o­vi­rus vec­tors for ­gene trans­fer ­because of ­their abil­ity to accom­plish effi­cient in vivo ­gene trans­fer. Adenovirus vec­tors encod­ing the ­genes for a varie­ty of anti­gens/recep­tors (car­cin­oem­bryon­ic anti­gen, gas­trin-releas­ing pep­tide recep­tor, som­a­tos­ta­tin recep­tor sub­type 2 (SSTr2)) ­have all ­shown ­that ­their expres­sion is ­increased on can­cer ­cells ­both in ­vitro and in ­vivo fol­low­ing aden­o­vi­rus infec­tion. Of par­tic­u­lar inter­est has ­been the aden­o­vi­rus encod­ing for SSTr2 (AdCMVSSTr2). Various radio­iso­topes ­have ­been ­attached to som­a­tos­ta­tin ana­logues for imag­ing and ther­a­py of SSTr2-pos­i­tive ­tumors ­both clin­i­cal­ly and in ani­mal mod­els. The use of ­these ana­logues in com­bi­na­tion ­with AdCMVSSTr2 is a prom­is­ing ­approach for improv­ing the detec­tion sen­si­tiv­ity and ther­a­peu­tic effi­ca­cy of ­these radio­lab­eled pep­tides ­against sol­id ­tumors. In addi­tion, we ­have pro­posed the use of SSTr2 as a mark­er for imag­ing the expres­sion of ­another can­cer ther­a­peu­tic trans­gene (e.g. cyto­sine deam­i­nase, thy­mi­dine ­kinase) encod­ed with­in the ­same vec­tor. This ­would ­allow for non-inva­sive mon­i­tor­ing of ­gene deliv­ery to ­tumor ­sites.

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