Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Our plain-English summary of Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft, by V. Izquierdo-Sánchez, S. Muñiz-Hernández, H. Vázquez-Becerra, et al (Molecules, 2018).

The study

• Authors: V. Izquierdo-Sánchez, S. Muñiz-Hernández, H. Vázquez-Becerra, J. Pacheco-Yepez, M.E. Romero-Piña, O. Arrieta, L.A. Medina
• Journal: Molecules
• Published: 2018;23(12)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

In plain English

This was a laboratory and animal study from Mexico City. It measured how nimotuzumab, an antibody aimed at a receptor called EGFR, bound to malignant pleural mesothelioma cells and spread in the body once made radioactive. It did not test the drug as a treatment or study asbestos exposure. The authors attached radioactive gallium-67 to the antibody. The labeling efficiency was 45%, the radiochemical purity was 92.4%, and about 98% stayed labeled in human serum after 72 hours. In cell tests, 21.6% of the labeled antibody bound to mesothelioma cells (MSTO-211H), versus 34.5% for high-EGFR cells and 6.9% for normal lung cells. Three mice with mesothelioma tumors grown under the skin were injected and scanned over 48 hours. Tumor uptake stayed roughly constant, with no statistical differences between time points. Tumor-to-liver ratios were above five, and uptake within the tumors was uneven. At 48 hours the tumor held 14% of the injected dose per gram and the stomach held 20%. The authors named the small number of animals as the main limitation. They concluded that the results should motivate further imaging studies toward use in patients.

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: Preclinical laboratory study: radiolabeling of an antibody, cell binding tests, and an animal experiment with imaging and organ measurements in mice carrying human mesothelioma tumors (xenografts)
• Who was studied: Three male athymic nude mice, 5 to 6 weeks old, obtained in Mexico City, injected under the skin with MSTO-211H human biphasic mesothelioma cells. Cell tests also used A431 cells (high EGFR) and MRC-5 normal lung cells.
• Exposure: No asbestos exposure was studied. The mice received an intravenous injection of the anti-EGFR antibody nimotuzumab labeled with gallium-67 (7.4 MBq, 50 µg). A control group received free gallium-67 chloride.
• Main results:
  • The radiochemical purity of the labeled antibody was 92.4 plus or minus 1.4% (5 preparations). Labeling efficiency was 45 plus or minus 4%. Stability in human serum after 72 hours was about 98%.
  • In cell binding tests, binding efficiency was 6.9 plus or minus 0.3% in MRC-5 normal lung cells, 34.5 plus or minus 1.9% in A431 cells (high EGFR), and 21.6 plus or minus 1% in MSTO-211H mesothelioma cells.
  • In the 3 mice, tumor uptake was constant over 48 hours, with no statistical differences between time points. Values ranged from 1.44 to 1.82%, with the apparent maximum at 24 hours.
  • The ratio of uptake in tumor to uptake in liver was greater than five at all imaging times (1, 12, 24 and 48 hours).
  • Uptake of the labeled antibody within tumor tissue was not even at any time point.
  • At 48 hours, organ measurements in the 3 mice showed 14% of the injected dose per gram in the tumor. Other organs: stomach 20%, spleen 9%, large intestine 7%, bladder 7%, lungs 6%, kidneys 5%, liver 3%, heart 3%, small intestine 3%.
  • Free gallium-67 chloride (control) accumulated in liver and bowel, with low accumulation in the tumor.
• The authors' conclusion: The authors concluded that they had presented a standardized method for labeling nimotuzumab with gallium-67 without significant loss of immunoreactivity. They said the biodistribution and tumor uptake results should motivate further imaging studies to explore its potential use as a theranostic biomarker in clinical studies of patients with malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors stated that the main limitation was the small number of animals (3) in the experiment.

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: Pleural Mesothelioma, Pleura, Occupational Exposure, Surgical Resection, Chemotherapy, EGFR, Mesothelioma, Biomarker.

Related studies

• HER1-targeted 86Y-panitumumab possesses superior targeting characteristics than 86Y-cetuximab for PET imaging of human malignant mesothelioma tumors xenografts — T.K. Nayak, K. Garmestani, et al. (2011)
• Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index in mesothelioma xenografts — P.M. Tedeschi, Y.K. Kathari, et al. (2014)
• Pulmonary uptake of gallium-67 in asbestos-exposed humans and sheep — R. Bégin, A. Cantin, et al. (1983)
• Unexpected gallium uptake in benign pulmonary pathology. Report of two cases — R.G. McLean, D. Choy, et al. (1984)
• Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice — D.J. Colin, O. Bejuy, et al. (2019)
• Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy — Y. Wang, X. Wang, et al. (2015)

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