89Zr-cetuximab PET imaging in patients with advanced colorectal cancer

Abstract

Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of 89Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq 89Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients 89Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.

Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach

“…This is in agreement with the results in advanced colorectal cancer [25], where also 6 days post-injection was described as optimal imaging time point. The imaging time point did not influence the average peak or maximum uptake; the improvement in TBR between the time points is due to a decrease in background activity.…”

Personalizing NSCLC therapy by characterizing tumors using TKI-PET and immuno-PET

“…a large number of extratumoral receptor molecules has to be saturated before tumor receptor molecules can be imaged. In such cases, simultaneous injection of cold doses of mAbs with radiolabeled mAbs is needed to improve image quality [22,23]. However, co-injection of cold mAbs also affects the quantification of tumor uptake as tumor target molecules become occupied with cold mAbs, thus decreasing accuracy of quantification.…”

“…This study did not investigate the predictive value of tracer uptake. The other clinical study was performed by Menke et al in 10 KRAS wild type colorectal cancer patients using a co-injection of [ 89 Zr]cetuximab and cold cetuximab [23]. Patients underwent 6 serial PET scans from 1 h to 10 days post injection.…”

Extracellular domain shedding influences specific tumor uptake and organ distribution of the EGFR PET tracer 89Zr-imgatuzumab

“…Many factors have been suggested for this mismatch, including perfusion rates, vascularity, vascular permeability, interstitial pressure and mAb plasma half-life [17]. Circulating HER2 extracellular domain (ECD) and trastuzumab are known to form complexes, which are swiftly cleared by the liver [18].…”