Introduction: CC49 is an antitumor monoclonal antibody that is promising for use in radioimmunoguided surgery (RIGS). However, the murine antibody has been limited by human antimouse antibody(HAMA) response and slow clearance. This study examined the pharmacokinetics and tissue localization of a humanized domain-deleted CC49 antibody (HuCC49ΔCH2 MAb) in humans. Methods: Twenty-one patients with colorectal carcinoma were given 1 mg intravenous (I.V.) bolus of HuCC49ΔCH2 MAb radiolabeled with 2 mCi 125I after thyroid blockade. The level of circulating HuCC49ΔCH2 MAb was measured daily as precordial counts using a handheld gamma-detecting probe. Each patient underwent an exploratory laparotomy on postinjection days 3–20. Gamma counts were measured at normal organs, aortic bifurcation (AB), and both clinically evident and occult tumors. Results: Precordial and AB gamma counts showed an excellent linear correlation. HuCC49ΔCH2 MAb followed a two-compartment pharmacokinetic model. Normal organs and AB showed similar exposures to HuCC49ΔCH2 MAb, while HuCC49ΔCH2 MAb favorably distributed into tumors from day 3. Intestinal and metastatic liver lesions showed the highest partition coefficients. All patients showed no HAMA response. Discussion: CH2 region deletion of HuCC49ΔCH2 MAb did not alter the pharmacokinetics compared to murine CC49. The favorable partition coefficient K of HuCC49ΔCH2 MAb into tumors supports its use in RIGS.
