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

Lindenberg L, Thomas A, Adler S, Mena E, Kurdziel K, Maltzman J, Wallin B, Hoffman K, Pastan I, Paik CH, Choyke P, Hassan R - Oncotarget (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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.

Show MeSH

Related in: MedlinePlus

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
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4414206&req=5

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

Mentions: For all patients and at all imaging time points, target lesion TBR was at least 1.2 (range 1.2− 62.0), which is considered the minimum TBR that can be visualized.17 Figure 1 shows mean TBR at 2–4 hours, 24–48 hours and at 96–168 hours for patients with mesothelioma and pancreatic adenocarcinoma. TBRs were higher for mesothelioma than pancreatic adenocarcinoma at all time points. Relative increases in TBR after 111In-amatuximab administration were also higher for mesothelioma. These differences however, were not statistically significant. As expected for monoclonal antibodies, tumor to blood pool ratios were low and ranged between 0.2 to 7.4 (mean 1.5).


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

Lindenberg L, Thomas A, Adler S, Mena E, Kurdziel K, Maltzman J, Wallin B, Hoffman K, Pastan I, Paik CH, Choyke P, Hassan R - Oncotarget (2015)

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
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414206&req=5

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
Mentions: For all patients and at all imaging time points, target lesion TBR was at least 1.2 (range 1.2− 62.0), which is considered the minimum TBR that can be visualized.17 Figure 1 shows mean TBR at 2–4 hours, 24–48 hours and at 96–168 hours for patients with mesothelioma and pancreatic adenocarcinoma. TBRs were higher for mesothelioma than pancreatic adenocarcinoma at all time points. Relative increases in TBR after 111In-amatuximab administration were also higher for mesothelioma. These differences however, were not statistically significant. As expected for monoclonal antibodies, tumor to blood pool ratios were low and ranged between 0.2 to 7.4 (mean 1.5).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

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.

Show MeSH
Related in: MedlinePlus