Sequential Use of lndium-111 Labeled Monoclonal Antibodies 96.5 and ZME-018 does not Increase Detection Sensitivity for Metastatic Melanoma

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Abstract
Two indium-111 labeled anti-melanoma murine monoclonal antibodies (MAb), 96.5 and ZME-018, each recognizing separate antigens on melanoma cells, were administered intravenously to 17 patients with melanoma in a sequential fashion to determine whether: 1) additional tumor sites could be imaged with the combination compared to a single MAb; 2) the first MAb influenced the biodistribution and tumor localization of the second; and 3) significant toxicity occurred with the combination. Patients were randomized to receive either 96.5, followed by ZME-018, ZME-018 followed by 96.5, or each MAb followed by itself (controls). Infusions of the second MAb occurred 10 days after the first infusion. Gamma camera images were obtained 72 hours after each antibody infusion. There were 139 known metastatic sites of which 72 lesions were localized by either MAb for an overall sensitivity of 52%. The detection rate was higher when lesions only greater than 1.5 cm were considered. Imaging results were independent of MAb administration sequence. When ZME-018 was given as the first infusion, 53% of known lesions were detected, compared to 34% when ZME-018 was given as a second infusion (p = NS). However, mean sensitivities using 96.5 as the first or second infusion were 48% and 66% respectively (p = NS). There was not a significant number of sites detected by MAb 2 that were missed by MAb 1. Human anti-murine antibody (HAMA) response occurred in seven of eight patients studied; two patients who experienced toxicity had levels of HAMA greater than 2000 ng/ml. We conclude that the use of these two murine anti-melanoma monoclonal antibodies given in sequential fashion did not significantly change the imaging sensitivity from that seen with each individual antibody. Moreover, with the exception of one patient, mean plasma half-life of the MAb did not change significantly, suggesting that overall clearance mechanisms were not saturated by the consecutive doses of monoclonal antibody or significantly altered by the presence of HAMA.

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