30 results on '"Lin, Wuu-Jyh"'
Search Results
2. 188Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells
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Luo, Tsai-Yueh, Cheng, Po-Ching, Chiang, Ping-Fang, Chuang, Ting-Wu, Yeh, Chung-Hsin, and Lin, Wuu-Jyh
- Published
- 2015
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3. Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [68Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter
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Farn, Shiou-Shiow, primary, Chang, Kang-Wei, additional, Lin, Wan-Chi, additional, Yu, Hung-Man, additional, Lin, Kun-Liang, additional, Tseng, Yu-Chin, additional, Chang, Yu, additional, Yu, Chung-Shan, additional, and Lin, Wuu-Jyh, additional
- Published
- 2021
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4. Design of PET Radiopharmaceuticals for Brain Imaging
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Hsu Jyh Ping, Lin Wuu Jyh, Li Ming Hsin, Shiue Chyng, Lin Jiang Jen, Farn Shiou Shiow, Lo Pro Long, Chang Kang Wei, Luo Tsai Yueh, Chen Jenn Tzong, Duh Ting Shien, and Chen Dow Che
- Subjects
Drug pharmacokinetics ,Positron ,Neuroimaging ,medicine.diagnostic_test ,In vivo ,business.industry ,Positron emission tomography ,Medicine ,General Medicine ,business ,Nuclear medicine ,Structural imaging - Abstract
Positron Emission Tomography (PET) is a multidisciplinary science. In contrast to CT and MRI, which are structural imaging techniques, PET is based on the characteristics of positron emitterslabeled radiopharmaceuticals and has been applied to study human pathophysiology in vivo non-invasively.
- Published
- 2019
5. Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [68Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter.
- Author
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Farn, Shiou-Shiow, Chang, Kang-Wei, Lin, Wan-Chi, Yu, Hung-Man, Lin, Kun-Liang, Tseng, Yu-Chin, Chang, Yu, Yu, Chung-Shan, and Lin, Wuu-Jyh
- Published
- 2021
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6. Evaluation of the Biological Behavior of a Gold Nanocore-Encapsulated Human Serum Albumin Nanoparticle (Au@HSANP) in a CT-26 Tumor/Ascites Mouse Model after Intravenous/Intraperitoneal Administration
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Chen, Chao-Cheng, primary, Li, Jia-Je, additional, Guo, Nai-Hua, additional, Chang, Deng-Yuan, additional, Wang, Chung-Yih, additional, Chen, Jenn-Tzong, additional, Lin, Wuu-Jyh, additional, Chi, Kwan-Hwa, additional, Lee, Yi-Jang, additional, Liu, Ren-Shyan, additional, Chen, Chuan-Lin, additional, and Wang, Hsin-Ell, additional
- Published
- 2019
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7. Molecular imaging, pharmacokinetics, and dosimetry of [sup.111]In-AMBA in human prostate tumor-bearing mice
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Ho, Chung-Li, Liu, I-Hsiang, Wu, Yu-Hsien, Chen, Liang-Cheng, Chen, Chun-Lin, Lee, Wan-Chi, Chuang, Cheng-Hui, Lee, Te-Wei, Lin, Wuu-Jyh, Shen, Lie-Hang, and Chang, Chih-Hsien
- Subjects
Tumors -- Physiological aspects -- Development and progression ,Prostate cancer -- Physiological aspects -- Development and progression ,Pharmacokinetics -- Research ,Radiation -- Measurement ,Diagnostic imaging -- Methods ,Biotechnology industry ,High technology industry - Abstract
Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-C[H.sub.2]CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-N[H.sub.2] (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of [sup.111]In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of [sup.111]In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8h. MicroSPECT/CT imaging studies suggested that the uptake of [sup.111]In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life ([t.sub.1/2a]) and the elimination half-life ([t.sub.1/2])of [sup.111]In-AMBA in mice were 1.53 h and 30.7 h, respectively. The [C.sub.m]ax and AUC of [sup.111]In-AMBA were 7.57% ID/g and 66.39 h* % ID/g, respectively. The effective dose appeared to be 0.11 mSv/[MBq.sup.-1]. We demonstrated a good uptake of [sup.111]In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. [sup.111]In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anti- cancer therapy., 1. Introduction Prostate cancer is estimated to rank first in number of cancer cases and second in number of deaths due to cancer among men in the Western world [1]. [...]
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- 2011
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8. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma
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Shih, Ying-Hsia, primary, Peng, Cheng-Liang, additional, Chiang, Ping-Fang, additional, Lin, Wuu-Jyh, additional, Luo, Tsai-Yueh, additional, and Shieh, Ming-Jium, additional
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- 2015
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9. 111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma
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Shih, Ying-Hsia, primary, Peng, Cheng-Liang, additional, Lee, Shin-Yu, additional, Chiang, Ping-Fang, additional, Yao, Cheng-Jung, additional, Lin, Wuu-Jyh, additional, Luo, Tsai-Yueh, additional, and Shieh, Ming-Jium, additional
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- 2015
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10. 188Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells
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Luo, Tsai-Yueh, primary, Cheng, Po-Ching, additional, Chiang, Ping-Fang, additional, Chuang, Ting-Wu, additional, Yeh, Chung-Hsin, additional, and Lin, Wuu-Jyh, additional
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- 2014
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11. Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
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Peng, Cheng-Liang, primary, Shih, Ying-Hsia, additional, Lin, Xi-Zhang, additional, Yeh, Chung-Hsin, additional, Shieh, Ming-Jium, additional, Lin, Wuu-Jyh, additional, and Luo, Tsai-Yueh, additional
- Published
- 2014
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12. Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma
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Wu, Shih-Yen, primary, Huang, Shih-Pin, additional, Lo, Yen-Chen, additional, Liu, Ren-Shyan, additional, Wang, Shyh-Jen, additional, Lin, Wuu-Jyh, additional, Shen, Chih-Chieh, additional, and Wang, Hsin-Ell, additional
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- 2014
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13. Tumor Burden Talks in Cancer Treatment with PEGylated Liposomal Drugs
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Lin, Yi-Yu, primary, Kao, Hao-Wen, additional, Li, Jia-Je, additional, Hwang, Jeng-Jong, additional, Tseng, Yun-Long, additional, Lin, Wuu-Jyh, additional, Lin, Ming-Hsien, additional, Ting, Gann, additional, and Wang, Hsin-Ell, additional
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- 2013
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14. Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role ofCa+2-Dependent Pathway
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Wang, Wei-Hsun, primary, Chiang, I-Tsang, additional, Ding, Kuke, additional, Chung, Jing-Gung, additional, Lin, Wuu-Jyh, additional, Lin, Song-Shei, additional, and Hwang, Jeng-Jong, additional
- Published
- 2012
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15. Molecular Imaging, Pharmacokinetics, and Dosimetry of111In-AMBA in Human Prostate Tumor-Bearing Mice
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Ho, Chung-Li, primary, Liu, I-Hsiang, additional, Wu, Yu-Hsien, additional, Chen, Liang-Cheng, additional, Chen, Chun-Lin, additional, Lee, Wan-Chi, additional, Chuang, Cheng-Hui, additional, Lee, Te-Wei, additional, Lin, Wuu-Jyh, additional, Shen, Lie-Hang, additional, and Chang, Chih-Hsien, additional
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- 2011
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16. Therapeutic Efficacy Evaluation of 111In-Labeled PEGylated Liposomal Vinorelbine in Murine Colon Carcinoma with Multimodalities of Molecular Imaging
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Chow, Tong-Hsien, primary, Lin, Yi-Yu, additional, Hwang, Jeng-Jong, additional, Wang, Hsin-Ell, additional, Tseng, Yun-Long, additional, Pang, Victor Fei, additional, Liu, Ren-Shyan, additional, Lin, Wuu-Jyh, additional, Yang, Chung-Shi, additional, and Ting, Gann, additional
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- 2009
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17. Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells.
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Luo, Tsai-Yueh, Cheng, Po-Ching, Chiang, Ping-Fang, Chuang, Ting-Wu, Yeh, Chung-Hsin, and Lin, Wuu-Jyh
- Abstract
Purpose: The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2. Materials and methods: Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control. Results: Our results indicated that Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner. Conclusion: Briefly, our study demonstrates that Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment. [ABSTRACT FROM AUTHOR]
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- 2015
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18. Molecular imaging, pharmacokinetics, and dosimetry of In-AMBA in human prostate tumor-bearing mice.
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Ho, Chung-Li, Liu, I-Hsiang, Wu, Yu-Hsien, Chen, Liang-Cheng, Chen, Chun-Lin, Lee, Wan-Chi, Chuang, Cheng-Hui, Lee, Te-Wei, Lin, Wuu-Jyh, Shen, Lie-Hang, and Chang, Chih-Hsien
- Abstract
Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH(2)CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of (111)In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of (111)In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of (111)In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t(1/2[alpha])) and the elimination half-life (t(1/2[beta])) of (111)In-AMBA in mice were 1.53 h and 30.7 h, respectively. The C(max) and AUC of (111)In-AMBA were 7.57% ID/g and 66.39 h % ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq(-1). We demonstrated a good uptake of (111)In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. (111)In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy. [ABSTRACT FROM AUTHOR]
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- 2011
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19. [123I]Iodooctyl fenbufen amide as a SPECT tracer for imaging tumors that over-express COX enzymes
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Huang, Ho-Lien, Yeh, Chun-Nan, Lee, Wei-Yuan, Huang, Ying-Cheng, Chang, Kang-Wei, Lin, Kun-Ju, Tien, Shu-Fan, Su, Wen-Chin, Yang, Ching-Hsiuan, Chen, Jenn-Tzong, Lin, Wuu-Jyh, Fan, Shio-Shio, and Yu, Chung-Shan
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IODINE isotopes , *AMIDES , *IODINE compounds , *RADIOACTIVE tracers , *TUMOR diagnosis , *CYCLOOXYGENASES - Abstract
Abstract: This study is concerned with the development of an agent for single photon emission computer tomography (SPECT) for imaging inflammation and tumor progression. [123I]Iodooctyl fenbufen amide ([123I]IOFA) was prepared from the precursor N-octyl-4-oxo-4-(4′-(trimethylstannyl)biphenyl-4-yl)butanamide with a radiochemical yield of 15%, specific activity of 37 GBq/μmol, and radiochemical purity of 95%. Analysis of the binding of [123I]IOFA to COX-1 and COX-2 enzymes by using HPLC and a gel filtration column showed a selectivity ratio of 1:1.3. An assay for the competitive inhibition of substrate transfer showed that IOFA exhibited a comparable IC50 value compared to fenbufen. In the normal rat liver, a lower level and homogeneous pattern of [123I]IOFA radioactivity was observed by SPECT. In contrast, in the rat liver with thioacetamide-induced cholangiocarcinoma, a higher uptake and heterogeneous pattern of [123I]IOFA radioactivity was seen as hot spots in tumor lesions by SPECT imaging. Importantly, elevated COX-1 and COX-2 expressions from immunostaining were found in the bile ducts of tumor rats but not of normal rats. Therefore, [123I]IOFA was found to exhibit the potential for imaging tumors that over-express COX. [Copyright &y& Elsevier]
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- 2013
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20. Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [ 68 Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter.
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Farn SS, Chang KW, Lin WC, Yu HM, Lin KL, Tseng YC, Chang Y, Yu CS, and Lin WJ
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- Animals, Autoradiography methods, Heterocyclic Compounds, 1-Ring chemical synthesis, Male, Rats, Rats, Sprague-Dawley, Time Factors, Tissue Distribution, Dopamine Plasma Membrane Transport Proteins metabolism, Gallium Radioisotopes chemistry, Heterocyclic Compounds, 1-Ring chemistry, Positron-Emission Tomography methods
- Abstract
Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [
99m Tc]TRODAT-1, [123 I]β-CIT, and [123 I]FP-CIT are commercially available;99 Mo/99m Tc generator is in short supply and123 I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating68 Ga, a radioisotope derived from a68 Ge/68 Ga generator., Methods: IPCAT-NOTA 22 was synthesized and labeled with [68 Ga]GaCl4 - at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats., Results: [68 Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68 Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68 Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5-15, 30-40, and 60-70 minutes, respectively, in NanoPET studies. The RCP% of [68 Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%., Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68 Ga]IPCAT-NOTA 24 uptake and transporter localization., Competing Interests: Shiou-Shiow Farn and Kang-Wei Chang are co-first authors. The authors declare that they have no conflicts of interest., (© 2021 Farn et al.)- Published
- 2021
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21. Preparation and therapeutic evaluation of (188)Re-thermogelling emulsion in rat model of hepatocellular carcinoma.
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Shih YH, Lin XZ, Yeh CH, Peng CL, Shieh MJ, Lin WJ, and Luo TY
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- Animals, Carcinoma, Hepatocellular pathology, Drug Combinations, Emulsions chemical synthesis, Emulsions chemistry, Hydrogels chemical synthesis, Hydrogels chemistry, Iodized Oil chemistry, Liver Neoplasms, Experimental pathology, Male, Organometallic Compounds chemistry, Polyethylene Glycols, Polyglactin 910, Radioisotopes chemistry, Rats, Rats, Sprague-Dawley, Rhenium chemistry, Survival Analysis, Tissue Distribution, Carcinoma, Hepatocellular radiotherapy, Emulsions therapeutic use, Hydrogels therapeutic use, Liver Neoplasms, Experimental radiotherapy, Radioisotopes therapeutic use, Rhenium therapeutic use
- Abstract
Radiolabeled Lipiodol(®) (Guerbet, Villepinte, France) is routinely used in hepatoma therapy. The temperature-sensitive hydrogel polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol triblock copolymer is used as an embolic agent and sustained drug release system. This study attempted to combine the polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol hydrogel and radio-labeled Lipiodol to form a new radio-thermogelling emulsion, rhenium-188-N,N'-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride-Lipiodol/hydrogel ((188)Re-ELH). The therapeutic potential of (188)Re-ELH was evaluated in a rodent hepatoma model. Rhenium-188 chelated with N,N'-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride was extracted with Lipiodol to obtain rhenium-188-N,N'-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride-Lipiodol ((188)Re-EL), which was blended with the hydrogel in equal volumes to develop (188)Re-ELH. The (188)Re-ELH phase stability was evaluated at different temperatures. Biodistribution patterns and micro-single-photon emission computed tomography/computed tomography images in Sprague Dawley rats implanted with the rat hepatoma cell line N1-S1 were observed after in situ tumoral injection of ~3.7 MBq (188)Re-ELH. The therapeutic potential of (188)Re-EL (48.58±3.86 MBq/0.1 mL, n=12) was evaluated in a 2-month survival study using the same animal model. The therapeutic effects of (188)Re-ELH (25.52±4.64 MBq/0.1 mL, n=12) were evaluated and compared with those of (188)Re-EL. The responses were assessed by changes in tumor size and survival rates. The (188)Re-ELH emulsion was stable in the gel form at 25°C-35°C for >52 hours. Biodistribution data and micro-single-photon emission computed tomography/computed tomography images of the (188)Re-ELH group indicated that most activity was selectively observed in hepatomas. Long-term (188)Re-ELH studies have demonstrated protracted reductions in tumor volumes and positive effects on the survival rates (75%) of N1-S1 hepatoma-bearing rats. Conversely, the 2-month survival rate was 13% in the control sham group. Therapeutic responses differed significantly between the two groups (P<0.005). Thus, the hydrogel enhanced the injection stability of (188)Re-EL in an animal hepatoma model. Given the synergistic results, direct (188)Re-ELH intratumoral injection is a potential therapeutic alternative for hepatoma treatment.
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- 2014
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22. Simultaneous imaging of temporal changes of NF-κB activity and viable tumor cells in Huh7/NF-κB-tk-luc2/rfp tumor-bearing mice.
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Wang WH, Chiang IT, Liu YC, Hsu FT, Chen HW, Chen CL, Lee YJ, Lin WJ, and Hwang JJ
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- Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Cell Line, Tumor, Cell Survival drug effects, Enzyme Activation drug effects, Humans, Mice, NF-kappa B antagonists & inhibitors, Neoplasms diagnosis, Neoplasms drug therapy, Neoplasms pathology, Niacinamide administration & dosage, Niacinamide analogs & derivatives, Niacinamide pharmacology, Phenylurea Compounds administration & dosage, Phenylurea Compounds pharmacology, Sorafenib, Transplantation, Heterologous, Tumor Burden drug effects, Gene Expression, Genes, Reporter, Molecular Imaging methods, NF-kappa B metabolism
- Abstract
Few studies have reported that the effect of sorafenib on advanced human hepatocellular carcinoma (HCC) is taking place via the inhibition of NF-κB signal transduction. Here we constructed a human HCC Huh7 stable clone with NF-κB-responsive element to drive dual reporter genes, herpes simplex virus thymidine kinase (tk) and firefly luciferase (luc2), and co-transfected with a third red fluorescent protein (rfp) gene, renamed as Huh7/NF-κB-tk-luc2/rfp cells, and combined with bioluminescent imaging (BLI) and red fluorescent protein imaging (RFPI) to monitor the effect of sorafenib on NF-κB activation and tumor inhibition. The results show that sorafenib could suppress the NF-κB-DNA binding activity, and the expression of downstream effector proteins. Notably, the relative photon fluxes obtained from RFPI and BLI, which represent the viable tumor cells and cells with NF-κB activation, decreased after sorafenib treatment by 50 to 65%, and 87.5 to >90%, respectively, suggesting that NF-κB activation is suppressed in viable HCC cells by sorafenib. Simultaneous molecular imaging of the temporal change of NF-κB activity and of viable cells in the same Huh7/NF-κB-tk-luc2/rfp tumors of the animal may reflect the real status of NF-κB activity and the viable tumor cells at the time of imaging.
- Published
- 2013
23. Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells.
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Chiang IT, Liu YC, Wang WH, Hsu FT, Chen HW, Lin WJ, Chang WY, and Hwang JJ
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- Base Sequence, Carcinoma, Hepatocellular enzymology, Carcinoma, Hepatocellular pathology, Cell Line, Tumor, DNA Primers, Electrophoretic Mobility Shift Assay, Humans, Liver Neoplasms enzymology, Liver Neoplasms pathology, Matrix Metalloproteinase 9 metabolism, Niacinamide analogs & derivatives, Phenylurea Compounds, Reverse Transcriptase Polymerase Chain Reaction, Sorafenib, Vascular Endothelial Growth Factor A metabolism, Benzenesulfonates pharmacology, Carcinoma, Hepatocellular metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Liver Neoplasms metabolism, Matrix Metalloproteinase 9 drug effects, NF-kappa B metabolism, Pyridines pharmacology, Tetradecanoylphorbol Acetate pharmacology, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up-regulation of nuclear factor-kappaB (NF-κB). Sorafenib can improve the overall survival in patients with HCC, however, the association of its inhibitory mechanisms with the inactivation of NF-κB remains unclear. Here, Huh7 cell line transfected with NF-κB-luc2 vector was used to study the effects of sorafenib on NF-κB activity, on expressions of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), which were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA increased the NF-κB activity and the expressions of MMP-9 and VEGF significantly, but its effects were suppressed by sorafenib in a dose-dependent manner. Similar results were found with PD98059, an inhibitor of extracellular signal-regulated kinase (ERK). Furthermore, transfection of Huh7 cell with an inhibitor of kappaB-α mutant vector, led to reduced TPA-induced MMP-9 and VEGF mRNA expressions. Sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-κB pathway in HCC cells.
- Published
- 2012
24. Curcumin-induced apoptosis in human hepatocellular carcinoma j5 cells: critical role of ca(+2)-dependent pathway.
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Wang WH, Chiang IT, Ding K, Chung JG, Lin WJ, Lin SS, and Hwang JJ
- Abstract
The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC). Here, we investigated the effects of Ca(2+) on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨ(m)), the increase of reactive oxygen species (ROS) production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca(2+) in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨ(m), ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium.
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- 2012
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25. Improvement of biodistribution and therapeutic index via increase of polyethylene glycol on drug-carrying liposomes in an HT-29/luc xenografted mouse model.
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Chow TH, Lin YY, Hwang JJ, Wang HE, Tseng YL, Wang SJ, Liu RS, Lin WJ, Yang CS, and Ting G
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- Animals, Antineoplastic Agents, Phytogenic pharmacology, Humans, Indium Radioisotopes, Liposomes, Luciferases genetics, Luminescence, Mice, Mice, Inbred NOD, Mice, SCID, Radiopharmaceuticals, Tissue Distribution, Tumor Cells, Cultured transplantation, Vinblastine pharmacokinetics, Vinblastine pharmacology, Vinorelbine, Antineoplastic Agents, Phytogenic pharmacokinetics, Colorectal Neoplasms drug therapy, Disease Models, Animal, Luciferases metabolism, Polyethylene Glycols pharmacokinetics, Vinblastine analogs & derivatives
- Abstract
Liposomes modified with a high concentration of polyethylene glycol (PEG) could significantly prolong the retention time of the carried drug in the circulation, thus improving the drug accumulation in the tumor. In this study, 6 mol% rather than 0.9 mol% PEGylated liposomes (100 nm in diameter) encapsulated with indium-111 were used in a human colorectal carcinoma HT-29/luc tumor-bearing mouse model for comparing the PEGylation effect. Pharmacokinetics, biodistribution, passive-targeted assay, bioluminescence imaging (BLI) and tumor growth measurements were used for the spatial and temporal distribution, tumor localization and therapeutic evaluation of the drug. Pharmacokinetic studies indicated that the terminal half-life (T((1/2))lambdaz) and C(max) of 6 mol% PEG (111)In liposomes were similar to those of 0.9 mol% PEG (111)In liposomes. In the blood, the total body clearance (Cl) of 6 mol% PEG (111)In liposomes was about 1.7-fold lower and the area under the curve (AUC) was 1.7-fold higher than those of 0.9 mol% PEG (111)In liposomes. These results showed that the long-term circulation and localization of 6 mol% PEGylated liposomes was more appropriate for use in the tumor-bearing animal model. In addition, the biodistribution of 6 mol% PEG (111)In liposomes showed significantly lower uptake in the liver, spleen, kidneys, small intestine and bone marrow than those of 0.9 mol% PEG (111)In liposomes. The clearance rate of both drugs from the blood decreased with time, with the maximum at 24 h post intravenous (i.v.) injection. Prominent tumor uptake and the highest tumor/muscle ratios were found at 48 h post injection. Both AUC and relative ratio of the AUCs (RR-AUC) also showed that 6 mol% PEGylated liposomes significantly reduced the uptake of drugs in the reticuloendothelial system (RES), yet enhanced the uptake in the tumor. Gamma scintigraphy at 48 h post injection also demonstrated more distinct tumor uptake with 6 mol% PEG (111)In liposomes as compared to that of 0.9 mol% PEGylated liposomes (p<0.01). BLI and in vivo tumor growth tracing showed that growth in tumor volume could largely be inhibited by 6 mol% PEG (111)In liposomes. The results suggest that 6 mol% PEGylated liposomes might be a more suitable liposomal carrier for drug delivery than 0.9 mol% PEGylated liposomes, not only by reducing the drug accumulation in the RES or its related organs, but by prolonging drug circulation and eventually enhancing the targeting efficiency in the tumor to reach a better therapeutic index.
- Published
- 2009
26. The value of 18F-FDG PET in the detection of stage M0 carcinoma of the nasopharynx.
- Author
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Yen TC, Chang JT, Ng SH, Chang YC, Chan SC, Lin KJ, Lin WJ, Fu YK, and Lin CY
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell secondary, Female, Humans, Male, Middle Aged, Nasopharyngeal Neoplasms secondary, Neoplasm Staging methods, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Severity of Illness Index, Single-Blind Method, Whole-Body Counting methods, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell pathology, Fluorodeoxyglucose F18, Nasopharyngeal Neoplasms diagnostic imaging, Nasopharyngeal Neoplasms pathology, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local pathology, Positron-Emission Tomography methods
- Abstract
Unlabelled: Distant metastasis is an important issue for nasopharyngeal carcinoma (NPC). The potential value of PET using 18F-FDG has not been well defined. This prospective study investigated the impact of 18F-FDG PET in NPC patients with stage M0 disease., Methods: From April 2001 to June 2003, 140 NPC patients (118 primary and 22 primary recurrent) with stage M0 (negative results from chest radiography, liver sonography, and whole-body bone scanning) underwent 18F-FDG PET to check for distant metastases. Confirmatory MRI or CT was performed if any abnormal 18F-FDG uptake was found at distant sites. The distant lesion was confirmed pathologically, if feasible, and was followed up clinically and with imaging for at least 6 mo., Results: 18F-FDG PET detected 26 true-positive metastatic sites in 18 (12.9%) of the 140 patients, among whom 14 had primary and 4 had recurrent tumors. The patient-based sensitivity and specificity of 18F-FDG PET for distant metastases were 100% and 86.9%, respectively. Mediastinal lymph nodes (n = 8) were the most common sites, followed by lung, liver, and bone (n = 5 each) and by other lymph nodes (n = 3). In patients with primary tumors, advanced nodal status (N2-3) was a statistically significant variable associated with development of distant metastases (P = 0.044). For recurrent NPC, neither age, sex, initial tumor stage, grade of differentiation, nor nodal stage showed a statistically significant difference between patients with and patients without distant metastases., Conclusion: 18F-FDG PET is valuable in avoiding aggressive locoregional radiotherapy in some NPC patients by the revelation of occult distant metastases, especially in patients with primary disease at a nodal stage of N2-3.
- Published
- 2005
27. Clinical usefulness of 18F-FDG PET in nasopharyngeal carcinoma patients with questionable MRI findings for recurrence.
- Author
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Ng SH, Joseph CT, Chan SC, Ko SF, Wang HM, Liao CT, Chang YC, Lin WJ, Fu YK, and Yen TC
- Subjects
- Adolescent, Adult, Aged, Carcinoma diagnosis, Female, Humans, Male, Middle Aged, Nasopharyngeal Neoplasms diagnosis, Neoplasm Recurrence, Local diagnosis, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Carcinoma diagnostic imaging, Carcinoma secondary, Fluorodeoxyglucose F18, Magnetic Resonance Imaging methods, Nasopharyngeal Neoplasms diagnostic imaging, Neoplasm Recurrence, Local diagnostic imaging, Positron-Emission Tomography methods
- Abstract
Unlabelled: It has been reported that 18F-FDG PET is highly sensitive for the detection of recurrent head-and-neck cancer. The objective of our prospective study was to validate the ability of this technique to detect the presence of tumors in primary, nodal, and distant sites as well as to assess its overall clinical usefulness in patients with questionable MRI findings for residual or recurrent nasopharyngeal carcinoma (NPC)., Methods: From January 2002 to October 2003, a group of 37 NPC patients whose postradiation follow-up MRI examination showed questionable residual or recurrent disease was assessed with 18F-FDG PET. 18F-FDG PET was interpreted visually. Disease at primary, nodal, and distant sites was assessed. The final diagnosis was confirmed histopathologically or with clinical and imaging follow-up of at least 6 mo., Results: Our results showed that the sensitivity and specificity of 18F-FDG PET for the detection of recurrent NPC were 91.6% and 76.0%, respectively, at the primary site; 90.0% and 88.9%, respectively, at nodal sites; and 100% and 90.6%, respectively, at distant sites. The overall sensitivity and specificity were 89.5% and 55.6%, respectively. Among the 37 patients, 18F-FDG PET added significant information to the MRI findings in 18, including offering true-negative findings in 10, revealing unexpected small metastatic adenopathy in 3, and disclosing distant metastatic foci in 5., Conclusion: 18F-FDG PET is highly sensitive and moderately specific for the detection of recurrent NPC in patients with questionable MRI findings. Overall, 18F-FDG PET appears to add significant information to MRI findings in about half of the NPC patients whose MRI examination shows questionable tumor recurrence.
- Published
- 2004
28. Defining the priority of using 18F-FDG PET for recurrent cervical cancer.
- Author
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Yen TC, See LC, Chang TC, Huang KG, Ng KK, Tang SG, Chang YC, Hsueh S, Tsai CS, Hong JH, Lin CT, Chao A, Ma SY, Lin WJ, Fu YK, Fan CC, and Lai CH
- Subjects
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Middle Aged, Neoplasm Recurrence, Local epidemiology, Positron-Emission Tomography statistics & numerical data, Prognosis, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Survival Analysis, Treatment Outcome, Uterine Cervical Neoplasms epidemiology, Fluorodeoxyglucose F18, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local therapy, Positron-Emission Tomography methods, Uterine Cervical Neoplasms diagnostic imaging, Uterine Cervical Neoplasms therapy
- Abstract
Unlabelled: PET with 18F-FDG has shown its potential in cervical cancer. For maximizing the benefits of this new imaging technology, we aimed to define the prognostic features of recurrent cervical cancer patients for selecting appropriate candidates using 18F-FDG PET., Methods: Patients enrolled were from 2 independent prospective studies investigating the role of 18F-FDG PET in cervical cancer patients after definitive treatment with documented failure (CTRP-018) or unexplained elevated tumor marker serum levels (CTRP-016) and proven relapse after PET. A total of 55 eligible patients received PET and CT or MRI. Lesion status was determined from pathologic results or clinical follow-up. The benefits calculated were based on treatment that was modified because of the PET findings. The Cox proportional hazards ratio (HR) was used to select independent prognostic covariates., Results: Thirty-six (65.5%) patients had treatment that was modified due to PET. Primary radiation (HR = 14.62; 95% confidence interval [CI] = 2.74-77.92), squamous cell carcinoma antigen (SCC-Ag) > or = 4 ng/mL (HR = 5.82; 95% CI = 1.53-22.04), and presence of symptoms (HR = 6.24; 95% CI = 1.99-19.61) at recurrence were significant factors associated with poor survival. A scoring system using these covariates defined 3 distinct prognostic groups: score < or = 1 (HR = 1.00); score = 2 (HR = 6.91; 95% CI = 1.49-32.14); and score = 3 (HR = 60.46; 95% CI = 9.68-378.09) (P < 0.0001)., Conclusion: Using this risk score, 18F-FDG PET may offer maximal benefits by selecting appropriate recurrent cervical cancer patients for salvage therapy with precise restaging information.
- Published
- 2004
29. 18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression.
- Author
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Yen TC, See LC, Lai CH, Yah-Huei CW, Ng KK, Ma SY, Lin WJ, Chen JT, Chen WJ, Lai CR, and Hsueh S
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell pathology, Female, Glucose Transporter Type 1, Humans, Middle Aged, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local pathology, Radionuclide Imaging, Radiopharmaceuticals pharmacokinetics, Reproducibility of Results, Sensitivity and Specificity, Statistics as Topic, Uterine Cervical Neoplasms pathology, Carcinoma, Squamous Cell diagnostic imaging, Carcinoma, Squamous Cell metabolism, Fluorodeoxyglucose F18 pharmacokinetics, Monosaccharide Transport Proteins metabolism, Uterine Cervical Neoplasms diagnostic imaging, Uterine Cervical Neoplasms metabolism
- Abstract
Unlabelled: This prospective study investigates the relationship between glucose transporter-1 (Glut-1) expression and PET images using (18)F-FDG and its uptake and compares them with the tumor status (primary vs. recurrent or persistent), initial grade of histologic differentiation, and International Federation of Gynecologic Obstetrics (FIGO) staging for cervical cancer patients., Methods: A dual-phase (18)F-FDG PET scan was performed on 51 participants within the 2 wk before surgery or biopsy. (18)F-FDG uptake was quantified by calculating standardized uptake values (SUVs). After (18)F-FDG PET scanning, 51 histologically proven squamous cell carcinoma specimens were examined to determine their degree of differentiation, using hematoxylin and eosin staining, and the expression of Glut-1 by an immunohistochemical stain. Twenty normal cervical and 20 cervical intraepithelial neoplasia (CIN) sets of tissue were also used to compare the results of Glut-1 expression in these tissues. The expression of Glut-1 was the product of (the intensity [with grades 0-3, defined qualitatively]) with (percentages of the lesion area that were positive). The results of Glut-1 expression were analyzed in combination with the SUVs (SUV1 was that at 40 min and SUV2 was that at 3 h), tumor status, initial cell differentiation, and FIGO staging., Results: Significant overexpression of Glut-1 was noted in 48 of the 51 (94.1%) cancer specimens. None or only minimal expression of Glut-1 was observed in basal layers of normal and CIN tissues. Significant positive correlation was observed between Glut-1 expression and the SUVs in cervical cancer specimens (r = 0.74, P < 0.000 for SUV1 and r = 0.65, P < 0.000 for SUV2). In recurrent or persistent tumor, tumor size was significantly associated with both Glut-1 expression (r = 0.508, P = 0.011) and SUV1 (r = 0. 456, P = 0.025). For recurrent or persistent tumor, only SUV1 reached statistical significance when compared with lymph node metastasis (P = 0.0226)., Conclusion: Glut-1 expression was related to (18)F-FDG uptake in cervical cancer patients. Recurrent or persistent cervical cancer tumor had significantly higher Glut-1 expression than metastatic lymph nodes. The values of SUV and the expression of Glut-1 did not correlate with the initial grade of histologic differentiation and FIGO staging.
- Published
- 2004
30. Delayed (18)F-FDG PET for detection of paraaortic lymph node metastases in cervical cancer patients.
- Author
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Ma SY, See LC, Lai CH, Chou HH, Tsai CS, Ng KK, Hsueh S, Lin WJ, Chen JT, and Yen TC
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Lymphatic Metastasis, Magnetic Resonance Imaging, Middle Aged, Prospective Studies, Time Factors, Uterine Cervical Neoplasms pathology, Fluorodeoxyglucose F18, Tomography, Emission-Computed, Uterine Cervical Neoplasms diagnostic imaging
- Abstract
Unlabelled: This prospective study investigated the usefulness of dual-phase (18)F-FDG PET scans (40 min and 3 h) in detecting paraaortic lymph node (PALN) metastasis for cervical cancer., Methods: One hundred four consecutive cervical cancer patients (International Federation of Gynecology and Obstetrics staging Ib-IVb, recurrent or persistent tumors) were included. All patients received a whole-body (18)F-FDG PET scan at 40 min and an additional scan from the T11 level to the inguinal region at 3 h after injection of 370 MBq (18)F-FDG. The maximum standardized uptake value (SUV) and retention index (RI [%], obtained by subtracting the normalized SUV value obtained at 40 min from that at 3 h) of the lesions were determined., Results: In all, 38 of the 104 patients were confirmed to have PALN metastases. For 31 patients (81.6%) with 13 upper (L1-L2 level) and 30 lower (L3-L4 level) PALNs, these metastases were detected with the 40-min scan. In addition, for 7 patients (18.4%) with 7 lower PALNs, metastases were found with the 3-h scan (RI = 12.6%). Two patients (3.0%) had 2 false-positive lesions initially (40 min) but were classified as benign with the 3-h scan. The sensitivity, specificity, and accuracy of (18)F-FDG PET scans at 40 min were 81.6%, 97.0%, and 91.3%, respectively. These quantities were all 100% when both the 40-min and 3-h scans were taken together. Eight patients (21.1%) had their treatment planning changed. We divided the 38 patients into 2 subgroups. Subgroup A included those with either only upper or only lower PALN metastases, and subgroup B included those with both upper and lower PALN metastases. In subgroup A, the SUV values were greater in the upper than in the lower PALNs in both the 40-min and 3-h images (P = 0.077). In subgroup B, there was no significant difference of SUV values between upper and lower PALNs in the 40-min (P = 0.433) and 3-h (P = 0.937) images., Conclusion: Our results showed that an additional 3-h scan is helpful for PALN detection of cervical cancer patients. A delayed image (3 h) is especially useful for lower PALN metastases.
- Published
- 2003
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