Radioimmunoguided Surgery techniques which use radiolabeled tumor specific markers and an intraoperative detector in an attempt to improve therapy and survival in patients with cancer have been under development for over fifteen years. Monoclonal antibody (MAb) CC49 is a second-generation murine IgG(1) which has improved localization properties over its predecessor MAb B72.3, and has been studied in a number of patients. In order to determine the pharmacokinetics of iodine-125 (I-125) CC49 MAb, size-exclusion, highperformance liquid chromatography (HPLC) was used to assess radioactive components in serum and urine following administration of the drug to colon cancer patients. Methods: Five patients received an intravenous infusion of 10mg of MAb CC49 labeled with 2mCi I-125. Following infusion, serum and urine specimens were collected from patients at predetermined time intervals prior to surgery. HPLC analysis of these specimens was completed to determine the radioactive species in each sample. Results: Serum and urine specimens showed that serum levels of CC49 decrease exponentially and become unmeasurable by day 14 (half-life 1.89 days, +/- 0.19), with a steady, low-level of free I-125 measurable in postinjection serum until day 21 after infusion. There was no evidence of MAb fragmentation or antibody:antigen (Ab:Ag) complex formation in serum, and no evidence of whole MAb, F(ab')(2), or Fab fragment excretion in urine. Preinjection sera with MAb added in vitro also failed to demonstrate Ab:Ag complex formation. Analysis of urine showed low level excretion of free I-125 which peaked by day 1 and declined exponentially through day 21, with a very low molecular weight (<1 kDa) MAb fragment excreted in urine between 1 and 21 days. Conclusion: Radioiodinated I-125 CC49 MAb remains in serum of cancer patients approximately 14 days, and tissue radioactivity beyond this time may reflect tissue sequestered MAb and/or free I-125 and not ''bloo pool'' radioactivity. CC49 MAb appears to be deiodinated in small but significant quantities before it is metabolized, and clearance of radioactivity is mainly in free I-125 form in urine. Mensurable quantities of a < 1 Kda MAb fragment in urine and not serum may suggest a renal mechanism of MAb metabolism, but may also represent a metabolic end product of MAb metabolism with a very short serum half-life (T-1/2) which accumulates in urine.
