A pharmacokinetic comparison of murine and chimeric forms of the 99mTc-labelled 174H.64 monoclonal antibody.

Abstract

The monoclonal antibody (MoAb) 174H.64 (Truscint SQ, Biomira Inc.) is a murine-derived MoAb reacting with an extracellular surface component of the cytoskeletal matrix ectopically expressed on squamous-cell carcinoma cell-surface membranes. A chimeric form of this MoAb has also been produced by genetically modifying the Fc portion of the MoAb by the insertion of a human Fc fragment. During this process the isotype was altered from an IgG1 (murine) to an IgG3 (chimeric). Pilot and phase I/II clinical trials of the murine and chimeric 99mTc-labelled 174H.64 MoAbs have been undertaken at selected European and North American sites. As part of this evaluation serum, urine and image data were collected at specific time intervals and used to obtain a kinetic model to describe the in vivo distribution of the MoAbs. A two-compartment model of the form: C(t) = C1 e-lambda 1t + Cz e-lambda zt was found to best describe the serum distribution of radioactivity of both the murine and chimeric MoAbs. The initial distribution half-lives were 2.9 +/- 0.7 hours and 2.7 +/- 0.2 hours, and the terminal elimination half-lives were 17.6 +/- 3.8 hours and 22.5 +/- 1.3 hours for the murine and chimeric MoAbs, respectively. No significant difference was found between the kinetic model parameters of two MoAbs at the 95% level. Assuming a similar clinical efficacy, these MoAbs could then be used interchangeably, with the chimeric MoAb offering potential advantages in reducing HAMA response.