Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using single photon emission computed tomography-computed tomography (SPECT-CT) imaging

Our plain-English summary of Safety and biodistribution of 111In-amatuximab in patients with mesothelin expressing cancers using single photon emission computed tomography-computed tomography (SPECT-CT) imaging, by L. Lindenberg, A. Thomas, S. Adler, et al (Oncotarget, 2015).

The study

• Authors: L. Lindenberg, A. Thomas, S. Adler, E. Mena, K. Kurdziel, J. Maltzman, B. Wallin, K. Hoffman, I. Pastan, C.H. Paik, P. Choyke, R. Hassan
• Journal: Oncotarget
• Published: 2015;6(6):4496-504
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This prospective, single-institution trial tested a radioactively labelled antibody, 111In-amatuximab, which targets the protein mesothelin, in patients with mesothelin-expressing cancers. Seven patients enrolled and six were imaged between October 2011 and February 2013. Four had malignant mesothelioma and two had pancreatic adenocarcinoma. Patients were scanned with SPECT/CT at 2–4 hours, 24–48 hours and 96–168 hours after injection. In every patient and at every time point, the tumor-to-background ratio was at least 1.2 (range 1.2 to 62.0), which the article describes as the minimum that can be visualized. Ratios were higher in mesothelioma than in pancreatic adenocarcinoma at all time points, but these differences were not statistically significant. The most strongly increased uptake was seen in two distant metastatic lesions. The liver received the highest estimated radiation dose (0.041 mGy/MBq), and no treatment-emergent adverse effects were observed. Serum CA125 rose significantly 14 days after injection (p = 0.03), while serum mesothelin did not change significantly. The authors concluded that the antibody localizes to primary and metastatic sites of these cancers. They named the small number of patients as a major limitation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective, single-institution imaging trial (biodistribution, dosimetry and safety study of a radiolabelled antibody)
• Who was studied: 7 patients enrolled and 6 imaged between October 2011 and February 2013: 4 with malignant mesothelioma and 2 with pancreatic adenocarcinoma. Median age was 66 (range 53–73); 2 were women and 4 were men. One patient was withdrawn because they could not lie flat on the scanner.
• Exposure: Not an asbestos exposure study. Patients received approximately 5 mCi of 111In-amatuximab intravenously. The first five patients were first given 50 mg of unlabelled amatuximab; the last patient received the radiotracer alone.
• Main results:
  • In all 6 imaged patients and at all imaging time points, target lesion tumor-to-background ratio was at least 1.2 (range 1.2 to 62.0), the minimum considered visible.
  • Tumor-to-background ratios were higher in the 4 mesothelioma patients than in the 2 pancreatic adenocarcinoma patients at all time points, but the differences were not statistically significant.
  • Strongly increased uptake was seen in two distant metastatic lesions: the left external iliac node in patient 2 and a gastroesophageal mass in patient 3. Uptake in primary tumor sites was more modest.
  • The estimated effective dose was 0.15 mSv/MBq. The liver received the highest absorbed dose (0.041 mGy/MBq), followed by the stomach wall (0.023 mGy/MBq).
  • No treatment-emergent adverse effects were observed. Of the 4 patients with no detectable human antichimeric antibodies (HACA) at baseline, 3 developed low titers two weeks after the radiotracer.
  • In the 6 patients, serum CA125 increased significantly from a mean of 303 before injection to a mean of 494 fourteen days after (p = 0.03). Serum mesothelin levels before and after were not significantly different (p = 0.16).
• The authors' conclusion: The authors concluded that a radiolabelled anti-mesothelin monoclonal antibody localizes to the primary and metastatic sites of mesothelin-expressing cancers, and that 111In-amatuximab was well tolerated with a favorable dosimetry profile.
• Limitations the authors state:
  • The small number of patients assessed
  • Pathologic confirmation of mesothelin expression was not required for study entry in pancreatic adenocarcinoma and mesothelioma
  • Variability in post-injection imaging time points and use of organ volume approximation for dosimetry estimates

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Monoclonal Antibody, Mesothelioma, Adenocarcinoma.

Related studies

• Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin expressing tumors — R. Misri, K. Saatchi, et al. (2011)
• A novel PET imaging using ⁶⁴Cu-labeled monoclonal antibody against mesothelin commonly expressed on cancer cells — K. Kobayashi, T. Sasaki, et al. (2015)
• Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors — Y. Fujisaka, T. Kurata, et al. (2015)
• Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce Immunogenicity for Treatment of Mesothelin-Expressing Tumors — R. Mazor, J. Zhang, et al. (2015)
• Asymmetrically increased rib cage uptake on bone scintigraphy: Incidental detection of pleural mesothelioma on single photon emission computed tomography/computed tomography — V.S. Dhull, P. Sharma, et al. (2014)
• Pan-cancer profiles of mesothelin (MSLN) unveil diagnostic potential and therapeutic targetability of pancreatic adenocarcinoma — M.R. Sheikh, B. Mistry, et al. (2026)

Browse more research in Oncotarget, or return to medical research.