Yu-Hsien Wu

National Chiao Tung University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (10)24.32 Total impact

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    ABSTRACT: The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.
    Nuclear Medicine and Biology 09/2011; 39(1):35-43. · 2.52 Impact Factor
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    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(1/2α)) and the elimination half-life (t(1/2β)) 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.
    BioMed Research International 01/2011; 2011:101497. · 2.71 Impact Factor
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    ABSTRACT: Fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine ((18)F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by (18)F-FDG and (18)F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 10(5) and 1 × 10(6) C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after (18)F-FDG and (18)F-FLT imaging. The biodistribution of (18)F-FDG and (18)F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, (18)F-FLT was superior to (18)F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that (18)F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.
    BioMed Research International 01/2011; 2011:535902. · 2.71 Impact Factor
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    ABSTRACT: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered (188)Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of (188)Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with (188)Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. In biodistribution, the highest uptake of (188)Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of (188)Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.
    International Journal of Nanomedicine 01/2011; 6:2607-19. · 4.20 Impact Factor
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    ABSTRACT: AMBA (DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)) is a bombesin (BN)-like peptide having high affinity with gastrin-releasing peptide receptors (GRPr).(177)Lu-AMBA is currently undergoing clinical trial as a systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. This study evaluated the biodistribution, pharmacokinetics, bioluminescent imaging (BLI) and microSPECT/CT imaging of (177)Lu-AMBA in PC-3M-luc-C6 luciferase-expressing human prostate tumour-bearing mice. Plasma stability of (177)Lu-AMBA could be maintained up to 55.67±6.07% at 24 h in a protection buffer. High positive correlations of PC-3M luc-C6 tumour growth in SCID mice between caliper measurement and BLI were observed (R(2)=0.999). Both the biodistribution and microSPECT/CT imaging in PC-3M-luc-C6 bearing-tumour mice showed that (177)Lu-AMBA in tumour uptake could be retained for 24 h. The distribution half-life (t(1/2α)) and the elimination half-life (t(1/2β)) of (177) Lu-AMBA in mice were 0.52 h and 26.6 h, respectively. These results indicated that BLI could be used to monitor the growth of tumour. High uptake of (177)Lu-AMBA in PC-3M-luc-C6 tumour-bearing mice by microSPECT/CT imaging can further evaluate the potential of (177)Lu-AMBA therapy for PC-3M-luc-C6 tumours.
    Anticancer research 10/2010; 30(10):4039-48. · 1.71 Impact Factor
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    ABSTRACT: Today, the Internet is very diversified, further complicating the classic NAT traversal problems. In order to solve these problems, there are many proposed methods classified into two categories. One enhances the NAT traversal techniques of applications, and the other tries to modify the behavior of NATs. In this article we focus on the former because NATs have been installed, and their behavior cannot be altered through endpoint users. Accordingly, in order to test NAT traversal techniques of five VoIP applications (Skype, MSN, Google Talk, X-Lite, and Linphone), three network topologies have been designed with two endpoints behind the same, different, or multilevel NATs. Through a series of experiments and from the experiment results, we observe that these VoIP applications use some traversal techniques, such as NAT mappedaddress probe, peer discovery, path check, and relay first, proposed by STUN, TURN, and ICE to make a direct connection when endpoints are behind the same or different NATs with independent mapping rules. However, with multilevel NATs, no endpoints can establish a direct connection when they use the above mentioned techniques, even if hairpin behavior is supported by NATs.
    IEEE Communications Magazine 01/2010; 48:58-65. · 3.66 Impact Factor
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    ABSTRACT: Nanoliposome can be designed as a drug delivery carrier to improve the pharmacological and therapeutic properties of drug administration. (188)Re-labeled nanoliposomes are useful for diagnostic imaging as well as for targeted radionuclide therapy. In this study, the in vivo nuclear imaging, pharmacokinetics and biodistribution of administered nanoliposomes were investigated as drug and radionuclide carriers for targeting solid tumor via intravenous (i.v.) administration. The radiotherapeutics ((188)Re-liposome) and radiochemotherapeutics ((188)Re-DXR-liposome) were i.v. administered to nude mice bearing human HT-29 colorectal adenocarcinoma xenografts. (188)Re-liposome and (188)Re-DXR-liposomes show similar biodistribution profile; both have higher tumor uptake, higher blood retention time, and lower excretion rate than (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylenediamine (BMEDA). In contrast to tumor uptake, the area under the curve (AUC) value of tumor for (188)Re-liposome and (188)Re-DXR-liposome was 16.5- and 11.5-fold higher than that of free (188)Re-BMEDA, respectively. Additionally, (188)Re-liposome and (188)Re-DXR-liposome had a higher tumor-to-muscle ratio at 24 h (14.4+/-2 .7 and 17.14+/-4.1, respectively) than (188)Re-BMEDA (1.6+/-0.1). The tumor targeting and distribution of (188)Re-(DXR)-liposome (representing (188)Re-DXR-liposome and (188)Re-liposome) can also be acquired by signal photon-emission computed tomography/computed tomography images as well as whole body autoradiograph. These results suggest that (188)Re-(DXR)-liposomes are potentially promising agents for passive targeting treatment of malignant disease.
    Anticancer research 01/2010; 30(1):65-72. · 1.71 Impact Factor
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    ABSTRACT: Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN in GRPR-expressing PC-3 tumor cells was 22.9 +/- 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA(1), Lys(3), Tyr(4)]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA(1), Lys(3), Tyr(4)]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.
    Cancer Biotherapy & Radiopharmaceuticals 09/2009; 24(4):435-43. · 1.44 Impact Factor
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    ABSTRACT: The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiotherapeutics of (188)Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel (188)Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.
    Nuclear Medicine and Biology 12/2008; 35(8):883-93. · 2.52 Impact Factor
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    ABSTRACT: Recombinant human factor IX (rhFIX) is a 56 kDa glycoprotein with full biological activity providing a guarantee of freedom from blood-borne viral contamination in the therapy of hemophilia B, but no data are available on the distribution of transgenic pig-produced rhFIX post injection (p.i.). Therefore, an 131I-radiolabeled rhFIX was developed to evaluate the distribution of rhFIX in rats. rhFIX was labeled with the lodogen method. 131I-rhFIX (25 microCi/25 microg/200 microl/rat) was intravenously injected through the tail vein in normal Sprague-Dawley (SD) rats and the biodistribution was examined from 5 min to 72 h p.i.. The pharmacokinetics were also evaluated from 5 min to 96 h p.i. The radiolabeled efficiency and radiochemical purity of 131I-rhFIX was over 96% and 98%, respectively. The biodistribution study showed that the rhFIX chiefly accumulated in the liver. The distribution and elimination half-life (t(1/2alpha) and t(1/2beta)) of 131I-rhFIX were 0.82 and 9.34 h, respectively. The maximum concentration in the plasma (Cmax) and the area under the concentration versus time curve (AUC(INF)) of 131I-rhFIX in rats were 3.09% injected dose (ID)/g and 15.3 h x % ID/g. The transgenic pig-produced rhFIX is mostly retained in the liver and the preclinical biodistribution and pharmacokinetic studies of 131I radiolabeled rhFIX are helpful for researching its biological effect in vivo.
    In vivo (Athens, Greece) 01/2008; 22(6):693-7. · 1.15 Impact Factor