Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging

Abstract

Amatuximab is a chimeric high-affinity monoclonal IgG1/k antibody targeting mesothelin that is being developed for treatment of mesothelin-expressing cancers. Considering the ongoing clinical development of amatuximab in these cancers, our objective was to characterize the biodistribution, and dosimetry of 111Indium (111In) radiolabelled amatuximab in mesothelin-expressing cancers. Between October 2011 and February 2013, six patients including four with malignant mesothelioma and two with pancreatic adenocarcinoma underwent Single Photon Emission Computed Tomography-Computed Tomography (SPECT/CT) imaging following administration of 111In amatuximab. SPECT/CT images were obtained at 2–4 hours, 24–48 hours and 96–168 hours after radiotracer injection. In all patients, tumor to background ratios (TBR) consistently met or exceeded an uptake of 1.2 (range 1.2–62.0) which is considered the minimum TBR that can be visualized. TBRs were higher in tumors of patients with mesothelioma than pancreatic adenocarcinoma. 111In-amatuximab uptake was noted in both primary tumors and metastatic sites. The radiotracer dose was generally well-tolerated and demonstrated physiologic uptake in the heart, liver, kidneys and spleen. This is the first study to show tumor localization of an anti-mesothelin antibody in humans. Our results show that 111In-amatuximab was well tolerated with a favorable dosimetry profile. It localizes to mesothelin expressing cancers with a higher uptake in mesothelioma than pancreatic cancer.

Phase I Study of DMOT4039A, an Antibody–Drug Conjugate Targeting Mesothelin, in Patients with Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

“…Finally, primary resistance to chemotherapy in pancreatic cancer may be more prevalent. To explore these possibilities, a companion imaging study (NCT01832116) using PET with the anti-mesothelin antibody conjugated to zirconium-89 was conducted, which demonstrated that primary pancreatic tumors accumulated less antibody than their respective metastases, whereas uptake was similar between ovarian tumors and their metastases (note: n ¼ 3 and n ¼ 2) consistent with previously published data (33). These preliminary observations suggest that relatively poor ADC uptake may be more relevant than primary resistance of pancreatic tumors (34).…”

ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment

“…study, in 4 patients with mesothelioma and 2 patients with pancreatic cancer. Here, 4 mCi 111 In-labeled MSLN antibody amatuximab was administered and subsequent SPECT showed uptake in pancreatic cancer lesions but a higher uptake in mesothelioma lesions (51).…”

Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors

“…Biodistribution and dosimetry of 111 In-amatuximab in 6 patients with mesothelin-expressing cancers (4 with malignant mesothelioma and 2 with pancreatic adenocarcinoma) was recently evaluated using Single Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) imaging [26]. 111 In-amatuximab targeted mesothelin-expressing cancer cells, with a clinically meaningful uptake in both primary tumors and metastatic sites of both tumor types, although a higher uptake was noted in mesothelioma than pancreatic cancer.…”