Diagnostic methods available for the detection, preoperative staging and post-therapeutic monitoring of patients with colorectal carcinoma remain deficient in both sensitivity and specificity. We have been studying one promising new diagnostic approach, immunoscintigraphy (IS, in these patients using an effective anti-colorectal carcinoma monoclonal antibody (MAb 1A3) labeled with 111In by a novel linking agent, BrphiHBED. Preliminary results from this ongoing study have been promising, particularly for the detection of rectal and rectosigmoid cancer deposits, but suggest a need for further improvements in sensitivity. We plan to evaluate two new radiopharmaceuticals developed in our laboratories that are likely to improve immunoscintigraphy. One of these, 64Cu-TETA-MAb1A3, will represent a completely novel first effort to combine the tumor- targeting specificity of a MAb with the superior imaging qualities, (i.e., high image contrast, quantification of tissue uptake and direct attenuation correction) of positron emission tomography (PET). the other, 123I-MAb 1A3 F(ab')2 will combine the advantages of MAb fragments, e.g. rapid clearance from normal tissues, with conventional planar scintigraphy and single- photon emission computed tomography (SPECT). Preclinical testing, including biodistribution studies, in a human colon cancer (GW39) hamster model have yielded excellent results and warrant these clinical trials. Additionally, new methods linking 64Cu and 99mTc to MAb 1A3 F(ab')2 and Fab' fragments will be evaluated in preclinical tests and, if promising, will be considered for clinical trials. We expect to be able to select a preferred MAb 1A3 radiopharmaceutical for IS in colorectal patients at the end of the first two years of this project. While these IS studies are in progress, we also will evaluate the emerging diagnostic approach of PET imaging using 18F-fluorodeoxyglucose - first, in a select group of patients with proven rectal or rectosigmoid cancer that are also being tested with IS, and then in a direct paired-comparison study to evaluate which is the preferred method for tumor imaging in these colorectal cancer patients. In the final year of this project, IS with our best radiopharmaceutical (64Cu, 123I, 111In, or perhaps 99mTc) coupled to MAb 1A3 will be compared with FDG-PET in 40 patients with suspected but unproven recurrent or metastatic rectal or rectosigmoid cancer. Taken in sum, these studies will thus provide a """"""""head-to-head"""""""" comparison of IS and FDG-PET, two techniques that show perhaps the greatest potential for advancing the diagnostic evaluation of such patients. At the completion of the three-year project we expect to have a definite answer regarding the diagnostic potential of radiolabeled MAb 1A3 for assessing patients with colorectal carcinoma and to have a strong indication of whether IS or PDG- PET is a preferred method for imaging these patients.
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