β Scribed by J. S. W. Stewart; V. Hird; D. Snook; M. Sullivan; M. J. Myers; A. A. Epenetos
No coin nor oath required. For personal study only.
The pharmacokinetics of intraperitoneal (i.p.) radiolabelled monoclonal antibody (MAb) was studied in 35 patients receiving 40 i.p. injections. Eleven patients received '"I-labelled MAb, 24 received ' OYlabelled MAb, and 5 patients received a second 1311 MAb treatment after having developed human anti-mouse antibodies (HAMA). All patients had blood and urine isotope activity monitored for 5 days after MAb injection. The radiation dose to bone marrow from the vascular compartment in the marrow was calculated by applying the MlRD formula to the measured blood activity. In HAMAnegative patients, peak blood isotope activity was observed at 40 hr post injection with a mean of 26% and 21 O/ o of the injected I 3 ' l and ' OY activity respectively. Sixty-five percent of the injected I 3 ' l activity, but only 12% of the administered ' OY. was excreted in the urine. Myelosuppression limited the administered I 3 ' l and ' OY activities to below 160 and 20 mCi respectively. In patients receiving I 3 ' l labelled MAbs, the marrow is irradiated by MAb within i t s circulation, producing myelosuppression that can be predicted by applying the MlRD formula to the blood isotope activity. This is not true for 9oY-labelled MAbs, where bone absorption of yttrium (which cannot be measured in patients) is the dominant radiation source for bone-marrow irradiation. Patients with HAMA present clear 1311 MAb rapidly with a decreased radiation dose to marrow and reduced myelosuppression. Giving patients intravenous antimouse immunoglobulin to clear '3'1-labelled MAb absorbed from the peritoneal cavity could decrease the toxicity observed in these patients. Patients receiving ' OY DTPA-chelated MAbs are unlikely to benefit, as catabolized yttrium is not excreted, and is concentrated in liver, spleen and bone. On the other hand, the use of i.v. chelating agents such as EDTA may scavenge non-proteinbound ' OY with increased excretion in the urine and less myelosuppression.
'HAMA-positive patients.
π SIMILAR VOLUMES
3'I-labelled HMFGl or HMFGl F(ab')2 monoclonal antibody (MAb) was administered intraperitoneally to I S patients with epithelial ovarian cancer who had completed chemotherapy and were in complete or good partial remission. Each patient received 2-3 mCi. Patients were scanned immediately after and un