Phase I clinical trial of the (131)I-labeled anticarcinoembryonic antigen CIGB-M3 multivalent antibody fragment.

Center for Genetic Engineering and Biotechnology (CIGB)-M3 is a trivalent recombinant single-chain Fv antibody fragment specific for carcinoembryonic antigen (CEA). Preclinical studies with radiolabeled CIGB-M3 have showed that the antibody fragment accumulates in human colon tumor xenografts growing in nude mice. A Phase I clinical trial was carried out to determine safety, biodistribution, and pharmacokinetics of the radiolabeled CIGB-M3 in two groups of patients with CEA+ colorectal cancers. Group I (10 patients) received a single intravenous injection of 0.3 mg of (131)I-CIGB-M3 (16.7-23.3 mCi/mg). Group II (7 patients) received 1 mg (5-7 mCi/mg). No adverse events related to the injected product were recorded, and no immunology response was detected up to 6 months after the injection. Tumors were detected in 15 of the 17 studied cases. The pharmacokinetic profile showed beta half-times of 14.1 and 6.3 hours for Groups I and II, respectively. Seventy-two (72) hours after the administration of the product, 85% of the total injected activity was excreted in urine in the form of free (131)I. The kidneys were identified as the organs that can limit the maximum tolerated dose. The (131)I-CIGB-M3 was safe in patients with colorectal cancer. The biodistribution and pharmacokinetic data suggest that the product can be further tested for molecular radiotherapy of CEA+tumors.

Activity optimization method in SPECT: a comparison with ROC analysis.

A discriminant method for optimizing activity in nuclear medicine studies is validated by comparison with ROC (received operating characteristic)-curves. The method is tested in 21 single photon emission computerized tomography (SPECT), performed with a cardiac phantom. Three different lesions (L(1), L(2) and L(3)) were placed in the myocardium-wall by pairs for each SPECT. Three activities (84, 37 or 18.5 MBq) of 99mTc were used as background. Linear discriminant analysis was used to select the parameters that characterize image quality among the measured variables in the images [(Background-to-Lesion (B/L(i)) and Signal-to-Noise (S(i)/N) ratios)]. Two clusters with different image quality (P=0.021) were obtained. The ratios B/L(1), B/L(2) and B/L(3) are the parameters used to construct the function with 100% of cases correctly classified into the clusters. The value of 37 MBq was the lowest tested activity for which good results for the B/L(i) ratios were obtained. The result coincides with the applied ROC-analysis (r=0.89).