Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin expressing tumors

Our plain-English summary of Evaluation of (111)In labeled antibodies for SPECT imaging of mesothelin expressing tumors, by R. Misri, K. Saatchi, S.S. Ng, et al (Nuclear Medicine and Biology, 2011).

The study

• Authors: R. Misri, K. Saatchi, S.S. Ng, U. Kumar, U.O. Häfeli
• Journal: Nuclear Medicine and Biology
• Published: 2011;38(6):885-96
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Mesothelin is expressed in many cancers, especially in mesothelioma and lung, pancreatic and ovarian cancers. In the present study, we evaluate (111)In labeled antimesothelin antibodies as an imaging bioprobe for the SPECT imaging of mesothelin-expressing tumors.

Methods: We radiolabeled the antimesothelin antibodies mAbMB and mAbK1 with (111)In using the p-SCN-bn-DTPA chelator. The immunoreactivity, affinity (K(d)) and internalization properties of the resulting two (111)In labeled antibodies were evaluated in vitro using mesothelin-expressing A431K5 cells. The biodistribution and microSPECT/CT imaging studies with (111)In labeled antibodies were performed in mice bearing both mesothelin positive (A431K5) and mesothelin negative (A431) tumors.

Results: In vitro studies demonstrated that (111)In-mAbMB bound with a higher affinity (K(d)=3.6±1.7 nM) to the mesothelin-expressing A431K5 cells than did the (111)In-mAbK1 (K(d)=29.3±2.3 nM). (111)In-mAbMB was also internalized at a greater rate and extent into the A431K5 cells than was the (111)In-mAbK1. Biodistribution studies showed that (111)In-mAbMB was preferentially localized in A431K5 tumors when compared to A431 tumors. At the low dose, the peak A431K5 tumor uptake of 9.65±2.65% ID/g (injected dose per gram) occurred at 48 h, while at high dose tumor uptake peaked with 14.29±6.18% ID/g at 72 h. Non-specific localization of (111)In-mAbMB was mainly observed in spleen.(111)In-mAbK1 also showed superior localization in A431K5 tumors than in A431 tumors, but the peak uptake was only 3.04±0.68% ID/g at 24 h. MicroSPECT/CT studies confirmed better visualization of A431K5 tumors with (111)In-mAbMB, than with (111)In-mAbK1.

Conclusion: SPECT imaging of mesothelin expressing tumors was demonstrated successfully. Our findings indicate that the antimesothelin antibody mAbMB has the potential to be developed into a diagnostic agent for imaging mesothelin-expressing cancers.

Copyright © 2011 Elsevier Inc. All rights reserved.

In plain English

This was a laboratory and mouse study, not a study of asbestos exposure or patients. The authors attached radioactive indium-111 to two antibodies, mAbMB and mAbK1, that bind mesothelin, a protein they note is expressed in mesothelioma and other cancers, and tested them as SPECT scan tracers. The tumors were not mesothelioma but human A431 cells, either engineered to carry mesothelin (A431K5) or without it, grown in male SCID mice. In cell tests, mAbMB bound mesothelin about 8 times more strongly than mAbK1. At the lower dose, mAbMB uptake in mesothelin tumors peaked at 9.65% of the injected dose per gram at 48 hours. At the higher dose it reached 14.29% per gram at 72 hours, against 4.93% per gram in tumors without mesothelin. mAbK1, whose tumor uptake was measured only at the lower dose, showed 3.04% per gram in mesothelin tumors at 24 hours. Much mAbMB collected in the spleen. Scans showed mesothelin tumors with better contrast using mAbMB. The authors concluded mAbMB was the better imaging choice, but that its spleen uptake needs to be better understood and addressed.

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: Laboratory (cell) experiments and animal experiments (biodistribution and microSPECT/CT imaging in mice) comparing two radiolabeled anti-mesothelin antibodies
• Who was studied: Male C.B-17 SCID mice, mostly in groups of 3 to 5, each bearing a mesothelin-positive A431K5 tumor (human epidermoid A431 cells transfected with the mesothelin gene) in the neck and a mesothelin-negative A431 tumor in the lower back. A group of 3 tumor-free mice was also studied, and cell tests used A431K5 cells. The work was done at the University of British Columbia, Canada. Study dates are not given.
• Exposure: No asbestos exposure was studied. The exposure was intravenous injection of indium-111-labeled antimesothelin antibodies, mAbMB and mAbK1. In the biodistribution experiments, both were given at a lower dose of about 4 μg/740 kBq, and mAbMB was also given at a higher dose of 7.4 to 10.1 MBq (50 μg/9.25 MBq). For the SPECT/CT scans, mice received 7.4 to 10.1 MBq of either antibody.
• Main results:
  • In cell tests, 111In-mAbMB bound mesothelin about 8 times more strongly than 111In-mAbK1 (Kd 3.6 nM versus 29.3 nM).
  • At 18 hours, 76.4±6.8% of cell-bound 111In-mAbMB had been taken into A431K5 cells, compared with 59±0.6% for 111In-mAbK1.
  • At the lower dose (740 kBq), uptake of 111In-mAbMB in mesothelin-positive A431K5 tumors peaked at 9.65±2.65% of injected dose per gram at 48 hours. Uptake in A431 tumors at that time was 4.7±1.65% ID/g.
  • At the higher dose, 111In-mAbMB uptake at 72 hours was 14.29±6.18% ID/g in A431K5 tumors and 4.93±2.84% ID/g in A431 tumors.
  • Biodistribution of 111In-mAbK1 was measured only at the lower dose (740 kBq). At 24 hours it showed 3.04±0.68% ID/g in A431K5 tumors and 2.22±0.41% ID/g in A431 tumors. A431K5 tumor uptake of 111In-mAbMB was significantly higher than that of 111In-mAbK1 at 24 hours (P=.005) and 72 hours (P=.002).
  • In tumor-bearing mice at the lower dose, 111In-mAbMB spleen uptake was 82.4±15.3% ID/g at 24 hours. In mice without tumors it was 8.06±0.70% ID/g.
  • MicroSPECT/CT scans gave better target-to-non-target ratios and image contrast of A431K5 tumors with 111In-mAbMB than with 111In-mAbK1.
  • Western blotting showed mesothelin in the A431K5 tumors but not in the A431 tumors or the spleen.
• The authors' conclusion: The authors concluded that mesothelin-expressing tumors in mice could be imaged by SPECT with indium-111-labeled antibodies. In their view, 111In-mAbMB was a better choice than 111In-mAbK1, although its non-specific uptake in the spleen needs to be better understood and addressed.
• Limitations the authors state:
  • Because only 2 mice were imaged with 111In-mAbK1, no statistical analysis was done on those image data.
  • The non-specific spleen uptake of 111In-mAbMB was not fully explained. The authors did not measure shed mesothelin in the tumor-bearing mice.
  • Spleen uptake could interfere with imaging of pancreatic tumors.
  • The reasons for the decline in tumor uptake at 72 and 96 hours were not established and would need more study.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Ovarian Cancer.

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