A Comparative Study of 157Gd and 10B Effect in a Carborane-Based Theranostic Agent for Membrane-Targeted Carbonic Anhydrase IX Inhibition and MRI-Guided Neutron Capture Therapy in Mesothelioma Treatment

Our plain-English summary of A Comparative Study of 157Gd and 10B Effect in a Carborane-Based Theranostic Agent for Membrane-Targeted Carbonic Anhydrase IX Inhibition and MRI-Guided Neutron Capture Therapy in Mesothelioma Treatment, by S. Rakhshan, A. Lanfranco, D. Alberti, et al (ACS Central Science, 2025).

The study

• Authors: S. Rakhshan, A. Lanfranco, D. Alberti, P. Renzi, A. Zarechian, S. Elkhanoufi, J.C. Cutrin, N. Protti, S. Geninatti Crich, A. Deagostino
• Journal: ACS Central Science
• Published: 2025;11(11):2215-2229
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This study investigates combined gadolinium and boron neutron capture therapy (GdBNCT) with carbonic anhydrase IX (CA IX) inhibition for mesothelioma treatment using a multifunctional platform (Gd-B-CA-SF). This platform incorporates a carborane cage for BNCT, a Gd complex for GdNCT/MRI, and a sulfamido group for CA IX inhibition. In vitro studies confirmed CA IX inhibition and selective binding of the compound to AB22 mesothelioma cells, with a 10-fold higher boron uptake compared to that in healthy Met-5a mesothelium. The combination of B and Gd in one molecule allows the exploration of potential additional effects coming from the nuclides 10B and 157Gd. Irradiation of AB22 cells showed complete tumor regrowth inhibition after treatment with 157Gd-10B-CA-SF, an effect strictly related to the presence of 157Gd and its localization on the cytosolic membrane. In vivo MRI studies confirmed higher accumulation of Gd-B-CA-SF in AB22 tumors in mice, demonstrating effective targeting. In vivo NCT experiments showed reduced tumor growth in 157Gd-10B-CA-SF treated mice, confirming the effectiveness of both 157Gd and 10B, even at relatively low concentrations. These results demonstrate the translational potential of Gd-B-CA-SF as a theranostic agent for an innovative approach to cancer treatment.

© 2025 The Authors. Published by American Chemical Society.

In plain English

This laboratory and mouse study tested an experimental compound, Gd-B-CA-SF, as a possible mesothelioma treatment. The compound combined boron and gadolinium, which capture neutrons in neutron capture therapy, with a group that blocks carbonic anhydrase IX, an enzyme on cancer cells. The gadolinium also shows up on MRI scans. Mouse mesothelioma cells (AB22) took up about ten times more boron than a human mesothelium cell line (Met-5a). After neutron irradiation in a reactor, AB22 cells given the version enriched in both gadolinium-157 and boron-10 had about 64% viability the next day, measured relative to untreated, non-irradiated control cells set at 100%. Over the following 15 days, these cells showed the strongest inhibition of regrowth, which the authors' abstract describes as complete. In mice with AB22 tumors under the skin, tumors treated with this version and irradiated (5 mice) grew significantly less than untreated, non-irradiated tumors (6 mice, p = 0.01). Irradiation alone gave a slight reduction that was not statistically significant. The compound also collected in the liver and kidneys. The authors concluded it has translational potential as a combined imaging and treatment agent. No asbestos exposure was studied.

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 study: chemical synthesis of a new compound, enzyme and cell-culture (in vitro) experiments, and animal experiments in a mouse tumor model
• Who was studied: Two cell lines, AB22 (murine mesothelioma) and Met-5a (immortalized human mesothelium). BALB/C mice with AB22 cells implanted under the skin of the lower neck. The in vivo neutron capture therapy experiment used 16 tumor-bearing mice: 5 treated and irradiated, 5 irradiated only, and 6 neither treated nor irradiated.
• Exposure: Not an asbestos exposure study. The exposures were the experimental compound Gd-B-CA-SF, made in natural-abundance and boron-10 and/or gadolinium-157 enriched versions (0.2 mM in cells; 0.1 mmol Gd/kg and 1 mmol B/kg in mice), followed by thermal neutron irradiation in the TRIGA Mark II reactor at the University of Pavia for 15 minutes.
• Main results:
  • Total boron in AB22 mesothelioma cells was 21 ± 3 μg/g, compared with 2.5 ± 0.7 μg/g in Met-5a mesothelium cells (Table 3). The authors describe this as a 10-fold higher uptake.
  • Attaching the gadolinium complex reduced the compound's overall ability to inhibit the carbonic anhydrase enzymes compared with the precursor CA-SF. The authors reported slightly greater selectivity for CA IX than for CA II.
  • In cell MRI images, signal enhancement was +57% ± 3 in AB22 cells and +14% ± 7 in Met-5a cells after incubation with 0.2 mM Gd-B-CA-SF.
  • One day after irradiation, viability of AB22 cells was close to control in all groups except those treated with the version enriched in both gadolinium-157 and boron-10, which had about 64% viability (p = 0.0149). Viability was calculated relative to untreated, non-irradiated control cells set at 100%.
  • Over 15 days, regrowth of irradiated AB22 cells was markedly inhibited with the gadolinium-157 enriched version, and even more with the version enriched in both gadolinium-157 and boron-10. The authors' abstract describes this cell-culture result as complete regrowth inhibition. With non-enriched compound, the neutron capture effect was negligible.
  • In mice, the maximum boron concentration in the tumor was about 13 ppm, with a tumor to healthy muscle ratio of 6.5 to 1. Only the liver and kidneys accumulated more gadolinium than the tumors.
  • Mice given the version enriched in both gadolinium-157 and boron-10 and then irradiated (n = 5) had significantly less tumor growth than non-irradiated, untreated control mice (n = 6), with p = 0.01 at the end point.
  • Mice that were irradiated without the compound (n = 5) showed a slight reduction in tumor growth that was not statistically significant compared with non-irradiated controls.
  • Blood urea nitrogen 24 hours after treatment was 18 ± 1 mg/dL in treated mice and 16 ± 2 mg/dL in PBS-treated mice (n = 3). Creatinine was below 0.4 mg/dL in both groups. Kidney tissue from treated mice showed a small number of vacuoles in tubule cells.
• The authors' conclusion: The authors concluded that Gd-B-CA-SF selectively targets mesothelioma cells and reduced tumor growth when enriched in gadolinium-157 and boron-10 and combined with neutron irradiation. They stated that this highlights its translational potential as a combined imaging and therapy (theranostic) agent.
• Limitations the authors state:
  • Gadolinium and boron concentrations measured by ICP-MS in tissue were lower than those estimated by MRI. The authors noted that comparing in vivo and ex vivo methods has methodological challenges.
  • The compound showed high uptake in the liver, which the authors called a drawback they suggest could be addressed by shielding.
  • The compound was only to a limited extent taken inside cells and largely stayed on the cell surface.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Mesothelium.

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