Pharmacokinetics, dosimetry and toxicity of rhenium-188-labeled anti-carcinoembryonic antigen monoclonal antibody, MN-14, in gastrointestinal cancer

The biodistribution, pharmacokinetics and dosimetry of (188)Relabeled MN-14, an IgG anti-carcinoembryonic antigen monoclonal antibody (MAb), were assessed in patients in advanced gastrointes tinal cancer. In addition, the dose-limiting toxicity (DLT) and maximum tolerated dose of fractionated doses of this agent were determined, Methods: Eleven patients were administered radioactive doses of directly labeled Re-188-MN-14 IgG, ranging from 20.5 mCi to 161.0 mCi (2.0 mg-4.9 mg). Ten of these patients received two or three MAb infusions, given 3-4 days apart, delivering total doses of 30 mCi/m(2)-80 mCi/m(2). External scintigraphy was used to evaluate the MAb biodistributionl and quantitative external scintigraphic methods were used to determine the organ and tumor radiation doses, Results: The biodistribution studies showed enhanced Re-188-MN-14 uptake in the liver, spleen and kidneys, compared to that of I-131-MN-14. The biological T-1/2 values for Re-188-MN-14 in the blood and whole body (in hours) were 8.2 +/- 4.1 (n = 7) and 107.8 +/- 104.2 (n = 9), respectively (mean +/- s.d.). The radiation absorbed doses (cGy/mCi) delivered to the total body, red marrow, lungs, liver, spleen and kidneys were 0.5 +/- 0.05, 3.6 +/- 1.6, 2.0 +/- 0.8, 5.9 +/- 2.5, 7.1 +/- 1.9 and 8.5 +/- 2.8, respectively. Red marrow suppression was the only DLT observed. The maximum tolerated dose of fractionated doses of Re-188-MN-14 was estimated to be 60 mCi/m(2). Conclusion: Despite its relatively increased renal and hepatic uptake, red marrow suppression is the only DLT of Re-188-MN-14. The feasibility of administering relatively high doses of Re-188-MN-14 completely outpatient basis may make this agent a preferred candidate for radioimmunotherapy.