This exploratory study was meant to assess clinical and safety data with a novel fibroblast activation protein inhibitor-based targeted theranostics as a salvage treatment option in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients who had progressed on tyrosine kinase inhibitors. Patients with metastatic RR-DTC who progressed on sorafenib/lenvatinib were prospectively recruited. If [Ga]Ga-DOTA.SA.FAPi positron emission tomography/computed tomography scan demonstrated moderate-to-excellent uptake in metastases, and patients had given informed consent, they received intravenous [Lu]Lu-DOTAGA.(SA.FAPi) as therapy at eight-weekly intervals. The primary endpoints were thyroglobulin (Tg) response and functional imaging response. The secondary endpoints were visual analog score (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status. The grading of toxicities was performed by using Common Terminology Criteria for Adverse Events (CTCAEV5.0). The sequential images were acquired by a dual-headed gamma camera, and dosimetric calculations were performed by using OLINDA/EXM V2.1. Fifteen patients were recruited [age: 55 ± 9 years (range: 39-67)]. [Lu]Lu-DOTAGA.(SA.FAPi) had median whole-body Teff of 88.06 hours (interquartile range [IQR]: 86.6-99). The colon was identified as a critical organ. The whole-body effective dose was 1.62E-01 ± 1.53E-02 mSv/MBq. A total of 45 cycles were administered, and the median cumulative administered activity was 8.2 ± 2.7 GBq (range 5.5-14 GBq). The median absorbed doses to the tumor lesions were 1.08E+01 (IQR: 4.16E+00 to 8.97E+01) mSv/MBq per cycle. The Serum Tg level significantly decreased after treatment [(median Tg: baseline-10,549 ng/mL (IQR: 3066.5-39,450) versus at the time of assessment: 5649 ng/mL (IQR: 939.5-17,099), = 0.0005)]. Molecular response assessment revealed no complete response; however, partial response was documented in four, and stable disease in three patients. The VASmax scores [pre-therapy: 9 (IQR: 8-10) versus follow-up: 6 (3-6) (-0.0001)], and ECOG [3, (IQR: 2-3 vs. 2, (IQR: 2-3) (-0.0078)] performance scores significantly improved after treatment. None of the patients experienced grade III/IV hematological, renal, or hepatotoxicity. These preliminary data suggest that the novel molecule [Lu]Lu-DOTAGA.(SA.FAPi) is safe, seems effective, and, most importantly, opens up a new avenue for the treatment of aggressive RR-DTC patients who have exhausted all standard line of treatments.
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http://dx.doi.org/10.1089/thy.2021.0412 | DOI Listing |
J Biochem
January 2025
Division of Cancer Cell Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
In this aging society, the number of patients suffering from age-related diseases, including cancer, is increasing. Cellular senescence is a cell fate that involves permanent cell cycle arrest. Accumulated senescent cells in tissues over time present senescence-associated secretory phenotype (SASP) and make the inflammatory context, disturbing the tumor microenvironment.
View Article and Find Full Text PDFJ Biomater Sci Polym Ed
January 2025
Department of Medical Affairs, Curie Sciences, Samastipur, Bihar, India.
Recently, there has been a great interest in the development of innovative wound dressing materials based on natural bioactives, as they can accelerate the healing process and address the issues related to traditional wound dressings. The current study focuses on developing a novel derivative of guar gum (GG) and gallic acid (GA) using a simple, free radical-mediated polymerization reaction aimed at enhancing the antioxidant properties of GG. Multiple spectroscopic investigations were performed to validate the GA-GG conjugate.
View Article and Find Full Text PDFFront Immunol
December 2024
Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background: Muscle-invasive bladder cancer (MIBC) is a prevalent cancer characterized by molecular and clinical heterogeneity. Assessing the spatial heterogeneity of the MIBC microenvironment is crucial to understand its clinical significance.
Methods: In this study, we used imaging mass cytometry (IMC) to assess the spatial heterogeneity of MIBC microenvironment across 185 regions of interest in 40 tissue samples.
Front Immunol
December 2024
Department of Urology, The Second People's Hospital of Meishan City, Meishan, Sichuan, China.
Background: Prostate cancer (PCa) is a multifactorial and heterogeneous disease, ranking among the most prevalent malignancies in men. In 2020, there were 1,414,259 new cases of PCa worldwide, accounting for 7.3% of all malignant tumors.
View Article and Find Full Text PDFClin Cosmet Investig Dermatol
December 2024
Plastic Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Peoples Republic of China'.
Background: Recent evidence suggests a crucial biological role for Circular RNAs (circRNAs) in keloid diseases, yet the underlying mechanisms remain unclear. This study explored the biological effects and molecular mechanisms of hsa_circ_0002198 in keloid formation.
Methods: Real-time quantitative PCR (qRT-PCR) was employed to assess the expression of circ_0002198 in keloid tissues, normal skin tissues, keloid fibroblasts (KFs), and normal skin fibroblasts (NFs) from nine patients.
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