Tc-Labeled tumor-associated glycoprotein 72 binding peptides G3-15 and T3-15

The tumor-associated glycoprotein 72 (TAG-72) is a high molecular weight mucigenous protein that is found mainly in the extracellular matrix of neoplastic tumors (1). This glycoprotein is usually not expressed in normal tissues but is overexpressed in the tumors of several cancers, such as those of the colon and rectum (colorectal cancer), stomach, pancreas, ovaries, prostate, lung, breast, etc. Therefore, TAG-72 is considered to have much theranostic value (useful for the diagnosis and/or therapy of a disease) because it can be used for antigen-directed surgical resection of cancerous tumors with radiolabeled anti-TAG-72 monoclonal antibodies (mAb) (1). In addition, the detection or absence of TAG-72 expression in colorectal cancer tumors was shown to have prognostic value because individuals who had complete removal of tumors with surgery guided by mouse anti-Tag-72 mAb were shown to have a long-term survival advantage compared to patients who had an incomplete removal of the lesions (2). However, the main limitation of using radiolabeled antibodies (Ab) or their fragments to detect and treat malignant tumors is the long circulation half-life of these molecules and the development of human anti-mouse antibodies in the patients (3). In comparison, synthetic anti-tumor peptides that can be used for the noninvasive imaging and therapy of cancers show rapid clearance from circulation and non-target tissue, have more access and deeper penetration into the lesions, and may not be immunogenic (3-5). Recently, the peptides GGVSCMQTSPVCENNL (A2-6) and NPGTCKDKWEICLLNGG (A3-10) were identified from a phase-display peptide library (f88-4/cys6) against TAG-72 and labeled with Tc to generate [Tc]-A2-6 and [Tc]-A3-10 (4). The labeled peptides were then evaluated in mice for the detection of LS-174T cell xenograft tumors that overexpress the TAG-72 antigen. In another study, two new peptides, FRERCDKHPQKCTKFL (G3-15) and DPRHCQKRVLPCPAWL (T3-15), which had a high affinity for the TAG-72 antigen, were identified when a modified procedure (from that used to purify the A2-6 and A3-10 peptides) was used to purify peptides from the f88-4/cys6 phage library (3). These peptides were then labeled with Tc to obtain [Tc]-G3-15 and [Tc]-T3-15, and the labeled compounds were tested for the detection of LS-174T cell xenograft tumors in mice. This chapter describes the results obtained with [Tc]-G3-15 and [Tc]-T3-15. Studies performed with [Tc]-A2-6 and [Tc]-A3-10 are described in a separate chapter of MICAD (www.micad.nih.gov) (6).