Optimal modification of panitumumab and trastuzumab with desferrioxamine chelator (DFO) for the development of 89Zr-immuno-PET tracers for HERs.

1108 Objectives In spite of the many imaging applications of the 89Zr labeled mAbs, there are no reported studies that indicate an optimal degree of modification of mAbs specifically with DFO for the development of the active forms of immuno-PET imaging agents. In order to produce improved quality immuno-PET imaging probe, it is necessary to determine the maximum possible extent of modification of mAb without compromising their bioactivity. In general, with an increase in the number of chelate per mAb or degree of labeling (DOL), specific activity (mCi/mg of mAb) of the probe increases but the specific binding of the probe decreases. Methods Two clinically approved HER-targeting mAbs panitumumab (HER1) and trastuzumab (HER2) were conjugated with desferrioxamine chelator with different conjugation ratios (DFO : mAb) 1 to 5. In-vitro receptor binding was performed for each conjugation using MDA MB 468 (HER1+) and MCF 7 (HER2+) cell lines. Specific activity was determined after labeling each conjugate with 89Zr. Based on the specific activity and corresponding cell binding results, number DFO chelate per mAb was optimized. Results Results showed that moving from DOL 1.0 to 2.0 although there was ~10 % loss of receptor binding but specific activity became almost double at DOL 2.0. Conclusions Therefore, the optimal number of DFO per mAb should be around 2.0. Funded by NCI/NIH, Contract No. HHSN261200800001E