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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.

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Related in: MedlinePlus

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

Mentions: Representative SPECT/CT images from a 53 year old man with mesothelioma after 111In-amatuximab administration is shown in Figure 2A–2D. Intense focal radiotracer uptake is observed in the left iliac node. Tumor from the left iliac lymph node showed strong membranous and cytoplasmic mesothelin expression. Figure 3A–3D shows representative SPECT/CT images from a 70 year old man with mesothelioma after 111In-amatuximab administration demonstrating modest radiotracer uptake in the right pleural mass. Strong membranous and cytoplasmic mesothelin expression was seen in more than 90% of tumor cells from the right pleural-based mass.


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)

Representative images showing tumor localization of 111In amatuximab and tumor expression of mesothelin in a 53 year old man with metastatic mesotheliomaCT (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).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Representative images showing tumor localization of 111In amatuximab and tumor expression of mesothelin in a 53 year old man with metastatic mesotheliomaCT (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).
Mentions: Representative SPECT/CT images from a 53 year old man with mesothelioma after 111In-amatuximab administration is shown in Figure 2A–2D. Intense focal radiotracer uptake is observed in the left iliac node. Tumor from the left iliac lymph node showed strong membranous and cytoplasmic mesothelin expression. Figure 3A–3D shows representative SPECT/CT images from a 70 year old man with mesothelioma after 111In-amatuximab administration demonstrating modest radiotracer uptake in the right pleural mass. Strong membranous and cytoplasmic mesothelin expression was seen in more than 90% of tumor cells from the right pleural-based mass.

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