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2. Optimization Processes of Clinical Chelation-Based Radiopharmaceuticals for Pathway-Directed Targeted Radionuclide Therapy in Oncology.

Author

Tomiyoshi, Katsumi, Wilson, Lydia J., Mourtada, Firas, Mourtada, Jennifer Sims, Namiki, Yuta, Kamata, Wataru, Yang, David J., and Inoue, Tomio

Subjects
DECAY schemes (Radioactivity), TISSUE viability, DISEASE management, OVERALL survival, RADIOBIOLOGY
Abstract

Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, 68Ga and 99mTc are the current standards for diagnostic radionuclides, while 177Lu and 225Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to 225Ac daughters 221Fr and 213Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose–response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Assessment of DNA/RNA Deregulation in Cancer Using 99mTc-Labeled Thiopurine.

Author

Chiu, Chuang-Hsin, Yang, David J., Liou, Yi-Chen, Chang, Wei-Chung, Yu, Tsung-Hsun, Chung, Min-Ching, Lee, Yen-Chun, Chen, Ing-Jou, Wang, Pao-Yeh, Lin, Ching-Po, Tsay, Hey-Jen, and Yeh, Skye Hsin-Hsien

Subjects
*RNA metabolism, *DNA metabolism, *IN vitro studies, *RADIOPHARMACEUTICALS, *T-test (Statistics), *STATISTICAL significance, *RESEARCH funding, *OVARIAN tumors, *BREAST tumors, *CHELATING agents, *APOPTOSIS, *DEOXY sugars, *EPIGENOMICS, *IN vivo studies, *IMMUNODIAGNOSIS, *CELL cycle, *MICE, *PURINES, *ANIMAL experimentation, *MOLECULAR structure, *TUMORS, *DATA analysis software, *CELL surface antigens
Abstract

Background: DNA biomarkers are useful for the assessment of tumor cell proliferation. The authors aimed to synthesize a thiopurine-based ligand for evaluation of nuclear uptake and tumor localization. Materials and Methods: A 2-hydroxypropyl spacer was incorporated between a chelator (cyclam) and thiopurine ligand to produce SC-06-L1. In vitro cellular uptake and the cell/media ratios of [99mTc]Tc-SC-06-L1 were assessed in breast (MCF-7, MDA-MB-231) and ovarian (TOV-112D, OVCAR3) cancer cells. The nuclear and cytosolic uptake ratio of [99mTc]Tc-SC-06-L1 was determined in OVCAR-3 and MCF-7 cells. Cytotoxicity assays and flow cytometric analysis of cell cycle apoptosis were conducted in cancer cells treated with SC-06-L1. Imaging was conducted in tumor-bearing mice; fluorine-18-2′-fluorodeoxyglucose ([18F]FDG) was used as a control. Results: The radiochemical purity of [99mTc]Tc-SC-06-L1 was >95%. [99mTc]Tc-SC-06-L1 exhibited higher cell-to-media ratios than [18F]FDG in cancer cells. [99mTc]Tc-SC-06-L1 had high uptake in the nuclear fractions in OVCAR-3 and MCF-7 cells, with nuclear/cytosolic ratios of 8 and 2, respectively. Cytotoxicity assays showed that SC-06-L1 was non-toxic compared with azathioprine in breast and ovarian cancer cells. Conclusions: [99mTc]Tc-SC-06-L1 was stable and involved in nuclear activities. [99mTc]Tc-SC-06-L1 showed non-toxic to cancer cells and exhibited fast kinetic uptake patterns for tumor imaging. [99mTc]Tc-SC-06-L1 represents a promising biomarker for imaging purine pathway-directed systems. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Radiopharmaceuticals

Author

Yang, David J., Inoue, Tomio, Kim, E. Edmund, Kim, E. Edmund, editor, Lee, Myung-Chul, editor, Inoue, Tomio, editor, and Wong, Wai-Hoi, editor

Published
2013
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14. Radiopharmaceuticals

Author

Yang, David J., Inoue, Tomio, Kim, E. Edmund, Kim, E. Edmund, editor, Lee, Myung-Chul, editor, Inoue, Tomio, editor, and Wong, Wai Hoi, editor

Published
2004
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20. East Meets West: Technology Training in the People's Republic of China.

Author

Garland, Virginia E. and Yang, David J.

Abstract

Discusses the growth of educational technology in China and describes computer training workshops that were held to increase computer literacy and to suggest critical ways of thinking about the use of computers in academic and administrative settings. Results of research on changes in technology use, including needs assessment surveys, are described. (Contains seven references.) (LRW)

Published
1994

41. Editorial

Author

Yang, David J. and Kim, E. Edmund

Published
2008

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