Purpose: To evaluate magnetic resonance (MR) imaging results after administration of gadolinium texaphyrin, a tumor-selective radiation sensitizer that is detectable at MR imaging, and to determine an appropriate intravenous dose of gadolinium texaphyrin for repeated injections during radiation therapy, the dose-limiting toxicity of reiterated doses of gadolinium texaphyrin, the maximal tolerated dose, the biolocalization of gadolinium texaphyrin (as assessed at MR examinations), and the response to treatment.
Materials And Methods: Ten daily intravenous injections of gadolinium texaphyrin, each followed by whole-brain radiation therapy (total of 10 fractions, 30 Gy), were administered to patients with brain metastases in a multicenter study. At the study institution, 11 patients underwent MR imaging before and after the first injection, after the 10th injection, and 8 weeks after entry into the study.
Results: MR imaging revealed selective drug uptake in metastases, without enhancement of normal brain tissue. In 10 patients, tumor uptake was higher after the 10th injection than after the first injection, which indicated accumulation of gadolinium texaphyrin in metastases. One lesion was visible only after the 10th injection and not at the pretherapeutic MR examination with injection of conventional gadolinium-based contrast material. Response to treatment was defined as a reduction in the size of the metastases between the preinjection MR study and the last MR study; seven patients achieved partial remission with tumor regression exceeding 50% of the initial size, and four achieved a minor response with less than 50% tumor regression.
Conclusion: These preliminary results indicate that gadolinium texaphyrin is tumor selective and that brain metastases can be depicted at MR imaging long after the administration of gadolinium texaphyrin.
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http://dx.doi.org/10.1148/radiology.212.3.r99se10755 | DOI Listing |
Discov Oncol
April 2024
Beckman Laser Institute, University of California, Irvine, CA, 92617, USA.
Purpose: Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled with the need to consider the tolerance of normal tissues and the potential effects on neurocognitive function, impose constraints on the amount of RT that can be safely delivered. A strategy for augmenting the effectiveness of RT involves the utilization of radiation sensitizers (RS).
View Article and Find Full Text PDFEur J Med Chem
March 2024
School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China. Electronic address:
Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2024
Department of Chemistry, The University of Texas at Austin, Austin, TX 78712-1224.
Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin () facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway.
View Article and Find Full Text PDFNat Commun
October 2023
Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, P. R. China.
Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks "Gd-Tex-lipids" to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors.
View Article and Find Full Text PDFCancers (Basel)
September 2022
Image-Guided Biomolecular Intervention Research and Division of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Background: Residual viable tumor cells after ablation at the tumor periphery serve as the source for tumor recurrence, leading to treatment failure. Purpose: To develop a novel three-dimensional (3D) multi-modal perfusion-thermal electrode system completely eradicating medium-to-large malignancies. Materials and Methods: This study included five steps: (i) design of the new system; (ii) production of the new system; (iii) ex vivo evaluation of its perfusion-thermal functions; (iv) mathematic modeling and computer simulation to confirm the optimal temperature profiles during the thermal ablation process, and; (v) in vivo technical validation using five living rabbits with orthotopic liver tumors.
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