Zr-nimotuzumab for immunoPET imaging of epidermal growth factor receptor I.

Rationale: Epidermal growth factor receptor (EGFR) upregulation is associated with enhanced proliferation and drug resistance in a number of cancers. Nimotuzumab is a humanized monoclonal antibody with high affinity for EGFR. The objective of this study was to determine if Zr-DFO-nimotuzumab could be suitable for human use as a PET probe for quantifying EGFR .

Methods: To evaluate the pharmacokinetics, biodistribution, microPET imaging, radiation dosimetry, and normal tissue toxicity in tumor and non-tumor bearing mice of Zr-desferoxamine-nimotuzumab (Zr-DFO-nimotuzumab) of a product prepared under GMP conditions. Nimotuzumab was conjugated to DFO and radiolabeled with Zr. Zr-DFO-nimotuzumab was characterized by gel-electrophoresis, biolayer interferometry (BLI) and flow cytometry. Zr-DFO-nimotuzumab was evaluated by microPET and by biodistribution in healthy and EGFR-positive tumor bearing mice.

Results: Flow cytometry with A431 cells showed no significant difference in the dissociation constant of nimotuzumab (13 ± 2 nM) compared with DFO-nimotuzumab (17 ± 4 nM). PET imaging in mice xenografts showed persistently high tumor uptake with the highest uptake obtained in DLD-1 xenograft (18.3 %IA/cc) at 168 hp.i. The projected human effective dose was low and was 0.184 mSv/MBq (0.679 rem/mCi) in females and 0.205 mSv/MBq (0.757 rem/mCi) in males. There was no apparent normal tissue toxicity as shown by cell blood counts and blood biochemistry analyses at 168-fold and 25-fold excess of the projected human radioactive and mass dose of the agent.

Conclusion: Zr-DFO-nimotuzumab had low organ absorbed dose and effective dose that makes it suitable for potential human use.