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

Clinical Trial

. 2015 Feb 28;6(6):4496-504.

doi: 10.18632/oncotarget.2883.

Anish Thomas 2, Stephen Adler 3, Esther Mena 4, Karen Kurdziel 1, Julia Maltzman 5, Bruce Wallin 5, Kimberly Hoffman 5, Ira Pastan 6, Chang Hum Paik 7, Peter Choyke 1, Raffit Hassan 2

Affiliations

Clinical Trial

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

Liza Lindenberg et al. Oncotarget. 2015.

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.

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Conflict of interest statement

Conflicts of interest

JM, BW and KH are employees of Morphotek, Inc. The other authors have no conflicts of interest.

Figures

Figure 1

Figure 1. Tumor to background ratios (mean and standard deviation) at 2–4 hours, 24–48 hours and at 96–168 hours after 111In amatuximab for patients with mesothelioma and pancreatic adenocarcinoma

Figure 2

Figure 2. Representative images showing tumor localization of 111In amatuximab and tumor expression of mesothelin in a 53 year old man with metastatic mesothelioma

CT (A), SPECT (B) and SPECT/CT (C) fusion image at 24 hours post-injection of 111In amatuximab showing focal uptake in the left iliac node (indicated by the red arrow). (D) Representative immunohistochemical staining of tumor from left inguinal lymph showing strong membranous and cytoplasmic staining for mesothelin in all tumor cells. Mesothelin staining is indicated by brown staining of tumor cells (20 X magnification).

Figure 3

Figure 3. Representative images showing tumor localization of 111In amatuximab and tumor expression of mesothelin in a 70 year old man with mesothelioma

CT (A), SPECT (B) and SPECT/CT (C) fusion image at 24 hours post-injection of 111In amatuximab showing mild uptake in the right pleural-based mass (arrows). High uptake in the liver, aorta and spleen are physiologic. The increased uptake at the skin level on the left side is the standard vial containing 111Indium. (D) Representative immunohistochemical staining of tumor from right pleural mass showing strong membranous and cytoplasmic staining for mesothelin in > 90% of tumor cells. Mesothelin staining is indicated by brown staining of tumor cells (20 X magnification).

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