Gene transfer strategies for improving radiolabeled peptide imaging and therapy

Utilization of molecular biology techniques offers attractive options in nu clear medicine for improving cancer imaging and therapy with radiolabeled p eptides, Two of these options include utilization of phage-panning to ident ify novel turner-specific peptides or single chain antibodies and gene tran sfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. Our group has focused on the latter approach for improv ing radiolabeled peptide imaging and therapy. The most widely used gene tra nsfer vectors in clinical gene therapy trials include retrovirus, cationic Lipids, and adenovirus. We have utilized adenovirus vectors for gene transf er 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 increas ed on cancer cells both in vitro and Irt vivoo following adenovirus infecti on. Of particular interest has been the adenovirus encoding for SSTr2 (AdCM VSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in an imal 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 o f another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allo Fc for non-invasive monitoring of gene delivery to tumor sites.