PURPOSE: Mesothelin (MSLN) is frequently overexpressed in pancreatic and ovarian cancers, making it a potential drug target. We performed an 89Zr-PET imaging study with MMOT0530A, a MSLN antibody, in conjunction with a phase I study with the antibody-drug conjugate DMOT4039A, containing MMOT0530A bound to MMAE. The aim was to study antibody tumor uptake, whole body distribution and relation between uptake, response to treatment and MSLN expression.
EXPERIMENTAL DESIGN: Before DMOT4039A treatment, patients received 37 MBq 89Zr-MMOT0530A followed by PET/CT imaging 2, 4, and 7 days post injection (pi). Tracer uptake was expressed as standardized uptake value (SUV). MSLN expression was determined with immunohistochemistry (IHC) on archival tumor tissue.
RESULTS: Eleven patients were included, seven with pancreatic and four with ovarian cancer. IHC MSLN expression varied from absent to strong. Suitable tracer antibody dose was 10 mg MMOT0530A and optimal imaging time was 4 and 7 days pi. Tumor tracer uptake occurred in 37 lesions with mean SUVmax of 13.1 (± 7.5) on PET 4 days pi, with 11.5 (± 7.5) in (N=17) pancreatic and 14.5 (± 8.7) in (N=20) ovarian cancer lesions. Within patients, a mean 2.4-fold (± 1.10) difference in uptake between tumor lesions existed. Uptake in blood, liver, kidneys, spleen and intestine reflected normal antibody distribution. Tracer tumor uptake was correlated to immunohistochemistry. Best response to DMOT4039A was partial response in one patient.
CONCLUSIONS: With 89Zr-MMOT0530A-PET pancreatic and ovarian cancer lesions as well as antibody biodistribution could be visualized. This technique can potentially guide individualized antibody-based treatment.