Pharmacokinetics, Dosimetry and Toxicity of Rhenium-188-Labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody, MN-14, in Gastrointestinal Cancer

• Published in: The Journal of nuclear medicine (1978) Vol. 39; no. 1; pp. 34 - 42
• Main Authors: Juweid, Malik, Sharkey, Robert M, Swayne, Lawrence C, Griffiths, Gary L, Dunn, Robert, Goldenberg, David M
• Format: Journal Article
• Language: English
• Published: Reston, VA Soc Nuclear Med 01.01.1998; Society of Nuclear Medicine
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Carcinoembryonic Antigen - immunology; Colonic Neoplasms - radiotherapy; Dose-Response Relationship, Radiation; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; Pancreatic Neoplasms - radiotherapy; Radiation therapy and radiosensitizing agent; Radioimmunotherapy; Radioisotopes - adverse effects; Radioisotopes - pharmacokinetics; Radioisotopes - therapeutic use; Radiotherapy Dosage; Rhenium - adverse effects; Rhenium - pharmacokinetics; Rhenium - therapeutic use; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tissue Distribution; Treatment with physical agents; Treatment. General aspects; Tumors; Human; Stomach; Radiolabelling; Maximal dose; Gut; Monoclonal antibody; Malignant tumor; Carcinoembryonic antigen; Immunoradiotherapy; Digestive diseases; Intestinal disease; Dosimetry; Rhenium; Pharmacokinetics; Gastric disease
• ISSN: 0161-5505; 1535-5667

The biodistribution, pharmacokinetics and dosimetry of 188Re-labeled MN-14, an IgG anti-carcinoembryonic antigen monoclonal antibody (MAb), were assessed in patients in advanced gastrointestinal cancer. In addition, the dose-limiting toxicity (DLT) and maximum tolerated dose of fractionated doses of this agent were determined. Eleven patients were administered radioactive doses of directly labeled 188Re-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/m2-80 mCi/m2. External scintigraphy was used to evaluate the MAb biodistribution, and quantitative external scintigraphic methods were used to determine the organ and tumor radiation doses. The biodistribution studies showed enhanced 188Re-MN-14 uptake in the liver, spleen and kidneys, compared to that of 131I-MN-14. The biological T(1/2) values for 188Re-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 188Re-MN-14 was estimated to be 60 mCi/m2. Despite its relatively increased renal and hepatic uptake, red marrow suppression is the only DLT of 188Re-MN-14. The feasibility of administering relatively high doses of 188Re on a completely outpatient basis may make this agent a preferred candidate for radioimmunotherapy.