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Biomedical subjects

D J Yang

Publications and source records attributed to D J Yang.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fluorine-18 fluoromisonidazole tumour to muscle retention ratio for the detection of hypoxia in nasopharyngeal carcinoma.

In vivo demonstration of hypoxia is of significance for tumour patient management. Fluorine-18 fluoromisonidazole ([18F]FMISO) is a proven hypoxic imaging agent. We developed an [18F]FMISO tumour to muscle retention ratio (TMRR) for the detection of tumour hypoxia in nasopharyngeal carcinoma (NPC). Data were acquired by positron emission tomography (PET) of the nasopharynx and neck after intravenous injection of 370 MBq of [18F]FMISO. Two imaging protocols were adopted: a long protocol for comprehensive dynamic information and a short protocol for a simple, clinically convenient imaging procedure. Tomograms were reconstructed and evaluated visually. ROI analysis on the basis of time-activity curve evaluation was performed to calculate the TMRR of NPC or cervical nodal metastases (CNMs) in relation to the suboccipital muscles at 2 h. The calculation of the TMRR was exactly the same for both the long and the short protocol as two 30-min composite frames had been created immediately after intravenous injection and 2 h after injection of [18F]FMISO in the long protocol. The normal tissue to muscle retention ratio (NTMRR) was derived similarly from the normal nasopharynx. The data of 12 controls and 24 patients with NPC were analysed. The long protocol was used in 15 patients, and the short protocol in nine. In controls, the mean NTMRR+/-1 SD was 0.96+/-0.14. The mean TMRRs for NPC and CNMs were 2.56+/-1.50 and 1.35+/-0.51, respectively; these values were significantly higher than the mean NTMRR for normal controls (P<0.005 in each case). At the retention threshold value of 1.24, tumour hypoxia occurred in 100% of the primary lesions of NPC and 58% of CNMs. The TMRR for undifferentiated carcinoma was significantly lower than that for non-keratinized carcinoma (P<0.05). The [18F]FMISO TMRR is a simple and clinically useful index for detecting tumour hypoxia in NPC.

Carcinoma↗
PubMed1996

Carcinoid tumors: imaging procedures and interventional radiology.

The hypervascular nature of carcinoid tumors and their metastases allows a more aggressive role by the radiologist in diagnosis and interventional management. Double-contrast gastrointestinal studies still best define the primary neoplasms. Appendiceal tumors, the most frequent site of carcinoids, frequently escape radiologic detection until large enough to be discovered by computed tomography (CT). Superior mesenteric arteriography of the small bowel and cecum is useful when the scanning procedures are not revealing. The "spokewheel" configuration of the desmoplastic mesenteric masses and lymph node metastases are best seen by CT, whereas hepatic metastases can be demonstrated by CT, CT-angioportography (CTAP), ultrasonography (US), magnetic resonance imaging (MRI), and octreotide scintigraphy. Percutaneous needle biopsy with radiologic guidance confirms the diagnosis of carcinoid tumors and their metastases. Hepatic arteriography is frequently performed in preparation for hepatic embolization or chemoembolization. Hepatic vascular occlusion therapy, the procedure of choice for the management of inoperable carcinoid liver metastases, results in a partial response in at least 50% of patients and a mortality rate of 5%. Chemoembolization with microencapsulated cytotoxic agents and direct percutaneous ethanol injection should also be considered for the treatment of liver metastases.

Angiography↗
PubMed1996

Biodistribution of cyclic carbonate of ioxilan: a radiopaque particulate macrophage imaging agent.

RATIONALE AND OBJECTIVES: A biodegradable radiopaque particulate contrast agent formulated from cyclic carbonate of ioxilan (IXC), which is a prodrug of nonionic water-solubel contrast ioxilan, recently has been developed. This contrast agent enhances liver attenuation and is cleared from the body as ioxilan. In the current study, we tested whether the biodistribution of IXC particles would be affected by the characteristics of particles. METHODS: IXC nanoparticles (average diameter = 290 nm) and IXC microparticles (average diameter = 1.7 mm) were prepared, characterized, and injected intravenously (i.v.; 50 mg I/kg body weight) into rats. Two sensitive, reproducible analytic methods--inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC)- were used to quantify tissue iodine and ioxilan concentrations. RESULTS: Both IXC nanoparticles and microparticles were taken up in the liver and spleen. The IXC nanoparticles remained in the liver at high concentrations for 6 hr and were slowly cleared. They also gave a high blood iodine concentration in the first 5 min after i.v. injection, suggesting their potential use as a blood-pool imaging agent. Unlike the nanoparticles, the microparticles had a significantly lower uptake by the kidney. CONCLUSION: Because of reduced renal uptake, microparticles are a preferred macrophage imaging agent. Biodegradable radiopaque particles may be used either as blood-pool imaging agents or as macrophage imaging agents depending on their size and distribution characteristics. The ICP-MS and HPLC methods are useful for biodistribution studies of iodinated contrast agents.

Animals↗
PubMed1996

Assessment of tumor cell proliferation using [18F]fluorodeoxyadenosine and[18F]fluoroethyluracil.

This study was to develop radiofluorinated ethyluracil (FEU) and deoxyadenosine analogues (FAD) for noninvasive assessment of tumor proliferative potential by positron emission tomography (PET). 5-(2-Fluoroethyl)uracil ([18F]FEU) was prepared by treating 2,4-dimethoxy-5-(2-hydroxyethyl)pyrimidine with K18F, followed by hydrolysis with HBr. Fluorodeoxyadenosine ([18F]FAD) was prepared by treating a triacetylated analogue of adenosine with K18F. In vitro cell proliferation assay of [18F]-FEU was performed using human peripheral blood mononucleus cells. Tissue distributions were studied in breast tumor-bearing rats at 0.5, 1, 2 and 4 h along with autoradiography at 45 min postinjection. PET imaging studies were conducted in VX-2 tumor-bearing rabbits. In vitro assay indicated that [18F]FEU incorporated into DNA/RNA during cell proliferation. Tumor-to-tissue count density ratios of [18F]FAD and [18F]-FEU increased as a function of time. [18F]FAD had higher tumor-to-nontumor tissue count density ratios than [18F]FEU. Autoradiograms of [18F]FEU and [18F]FAD, and PET images of [18F]FEU, showed that the tumors could be well visualized. The results suggest that [18F]FEU and [18F]FAD have potential use in evaluating tumor cell proliferation by PET.

Animals↗
PubMed1996

Synthesis, biodistribution, and estrogen receptor scintigraphy of indium-111-diethylenetriaminepentaacetic acid-tamoxifen analogue.

This study was aimed at developing a hydrophilic diethylenetriaminepentaacetic acid-tamoxifen (DTPA-Tam) analogue for use in imaging estrogen receptor positive (ER+) lesions. In rat uterine cytosol, the IC50 of DTPA-Tam conjugate was 1 microM and of tamoxifen, 2 microM. Biodistribution, autoradiography, and radionuclide imaging of 111In-DTPA-Tam in breast-tumor-bearing rats showed that tumor-to-tissue ratios increased steadily between 30 min and 48 h. The in vivo response of MCF-7 breast cancer xenografts to tamoxifen and DTPA-Tam in nude mice demonstrated that DTPA-Tam could reduce tumor growth rate. These results indicate that DTPA-Tam, a new hydrophilic ER+ ligand, might be useful in diagnosing ER+ lesions.

Animals↗
PubMed1996

Positron emission tomography using [18F]fluorotamoxifen to evaluate therapeutic responses in patients with breast cancer: preliminary study.

Positron emission tomography (PET) was used to assess the biodistribution and clinical usefulness of [18F]fluorotamoxifen (FTX) in 10 patients with estrogen-receptor(ER)-positive breast tumors. Ten patients with ER-positive breast cancer were prospectively studied, and the consecutive PET imagings (each takes 15 or 20 min) were obtained for 60 or 80 min after the injection of 88.8-392.2 MBq (2.4-10.6 mCi) of [18F]FTX. Twenty three suspected primary or metastatic lesions in 10 patients were evaluated and the tumor uptakes of [18F]FTX in nineteen tumor lesions were correlated to the response of tamoxifen therapy. Three lesions in three patients were considered to be truly negative for breast cancer on the bases of biopsy specimens and/or clinical course. Five (71.4%) of seven patients and 16 (80.0%) of 20 lesions were interpreted to be truly positive for breast cancer. The mean standardized uptake value (SUV) of the radiotracer in tumor was 3.0 on delayed images. There was no significant correlation between the standardized uptake values of [18F]FTX and the ER concentrations in primary lesions. Nineteen tumor lesions in six patients were evaluable to compare the [18F]FTX uptake with responses to tamoxifen therapy after the PET study. Three patients who had a good response to tamoxifen therapy showed positive lesions on PET images, whereas two of three patients who had a poor response showed negative lesions and one showed mixed results. There was no significant difference of [18F]FTX uptake in bone lesions between good and poor responders. However, when bone lesions were excluded, [18F]FTX uptakes in tumors with good responses were significantly higher than those with poor responses (mean and standard deviation of SUV: 2.46 +/- 0.62 vs 1.37 +/- 0.59, P < 0.05). PET imaging using [18F]FTX provides useful information in predicting the effect of tamoxifen therapy in patients with ER-positive breast cancer. Further study is warranted to confirm the clinical utility of PET using [18F]FTX in breast cancer patients.

Aged↗
PubMed1996

Percutaneous intratumoral injection of cisplatin microspheres in tumor-bearing rats to diminish acute nephrotoxicity.

Poly(D,L-lactide) microspheres loaded with cisplatin (PLA-CDDP MS) were prepared by a solvent evaporation technique for direct intratumoral injection. The microspheres, 50-100 microns, containing 40.04% of cisplatin produce sustained release in vitro. PLA-CDDP MS (6 mg/kg body weight of cisplatin) suspensions were injected intratumorally into mammary tumors in rats. Cisplatin solution (6 mg/kg body weight) was injected either intratumorally or intraperitoneally in two groups. After treatments, the tumor size decreased in each of the groups as a function of time. Sixteen days post-injection, the tumors had either disappeared or significantly shrunk. PLA-CDDP MS had a similar antitumor effect compared with cisplatin aqueous solution. Blood urea nitrogen, serum creatinine and histopathology examinations revealed that the renal toxicity in the PLA-CDDP MS group was significantly less than in the control groups. These results indicate that intratumoral injection of PLA-CDDP MS maintains anticancer potency and reduces acute renal toxicity.

Animals↗
PubMed1996

Synthesis and evaluation of water-soluble polyethylene glycol-paclitaxel conjugate as a paclitaxel prodrug.

Water-soluble paclitaxel may cause less side effects and be less costly to administer in comparison to a taxol formulation using a cremophor EL/alcohol vehicle. In this study, polyethylene glycol (PEG; MW 5000) was conjugated to the 2' position of paclitaxel through a spacer succinyl group. PEG-paclitaxel as a non-ionic paclitaxel prodrug was highly water soluble (> 20 mg equiv. paclitaxel/ml). The release of paclitaxel from phosphate-buffered solution was pH dependent. The half-life of PEG-paclitaxel was 7.6, 54 and 311 min at pH 9.0, 7.4 and 6.0, respectively. PEG-paclitaxel inhibited the growth of B16 melanoma cells to an extent similar to that of paclitaxel. In MCA-4 mammary tumor-bearing mice, a single dose of PEG-paclitaxel (40 mg equiv. paclitaxel/kg body weight) significantly delayed tumor growth. The average number of days for the tumor to reach 12 from 8 mm in diameter increased from 6.5 days for control animals to 8.5 days for PEG-paclitaxel-treated animals and 9.4 days for paclitaxel-treated animals. These studies demonstrated that PEG may be used as an effective solubilizing carrier for paclitaxel.

Animals↗
PubMed1996

Evaluation of [131I]iodoerythronitroimidazole as a predictor for the radiosensitizing effect.

The aim of this study was to evaluate whether radiolabeled iodoerythronitroimidazole (IETNIM) could predict the radiosensitization effect on tumors. Tumor-bearing mice were irradiated at a dose of 25, 31 and 37 Gy after the injection of IETNIM. They were also exposed to 37 Gy radiation at 35, 70, 140 and 240 min after the i.p. injection of IETNIM. After the irradiation, tumor growth assays were conducted and the effect of IETNIM as a radiosensitizer was estimated as enhancement factor (EF). Tumor uptake was measured at 35, 70, 140 and 240 min after i.p. injection of [131I]IETNIM, which were the same intervals used in the radiosensitization study. EF of IETNIM in mice treated with 25, 30 and 37 Gy irradiation was 0.72, 0.98 and 1.28, respectively. EF of IETNIM in mice irradiated at 35, 70, 140 and 240 min after the injection was 1.50, 1.69, 1.46 and 1.08, which corresponded to the tumor uptake and blood clearance of [131I]IETNIM. [131I]IETNIM may be a suitable radiopharmaceutical to predict the radiosensitization effect of misonidazole analogs on tumors.

Animals↗
PubMed1996

Development of new markers for hypoxic cells: [131I]Iodomisonidazole and [131I]Iodoerythronitroimidazole.

This study was aimed at developing ligands to evaluate tumor hypoxia by planar scintigraphy. Two 2-nitroimidazole analogues were developed as precursor compounds to image hypoxic tumors. Both tosylmisonidazole (Ts MISO) and tosylerythronitroimidazole (Ts ETNIM) were labeled with 131I. The biodistribution and autoradiographic evaluations by planar scintigraphy of 131I-IMISO and 131I-IETNIM were conducted at 1, 2 and 4 hours after administration to rats bearing 13762 breast tumors. Biodistribution of 131I-IMISO was also evaluated in Madison lung tumor-bearing mice. Intratumoral oxygen tension was measured by the Eppendorf system. Biodistribution showed similar tumor/blood and tumor/muscle count density ratios for both compounds. The thyroid uptake of both analogues was increased with time, suggesting in vivo deiodination probably occurred. Autoradiographs of 131I-IMISO and 131I-IETNIM revealed good visualization of the neoplasms. The tumor oxygen tension was 3-6 mmHg as compared to the normal tissue oxygenation of 30-40 mmHg. The findings indicate that these analogues can localize in the hypoxic region of solid tumors and may assist with quantitation of the hypoxic fraction of tumor for proper selection and evaluation of appropriate radiotherapy and chemotherapy.

Animals↗
PubMed1996

New isochromophilones VII and VIII produced by Penicillium sp. FO-4164.

New isochromophilones VII and VIII were isolated from the culture broth of Penicillium sp. FO-4164. The structures were elucidated as 6H-2-benzopyran-6,8(7H)-dione, 5-chloro-3-(3',5'-dimethyl-1',3'-heptadienyl)-1,7,8a-trihydro-7, 8a-dihydroxy-7-methyl-7-acetate for isochromophilone VII and 6H-2-benzopyran-6-one,5-chloro-3-(3',5'-dimethyl-1', 3'-heptadienyl)-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-8-acetate for isochromophilone VIII. Isochromophilones VII and VIII inhibited diacylglycerol acyltransferase activity with IC50 values of 20.0 and 127 microM and acyl-CoA: cholesterol acyltransferase activity with IC50 values of 24.5 and 47.0 microM, respectively.

Acyltransferases↗
PubMed1996

Pyripyropenes, novel ACAT inhibitors produced by Aspergillus fumigatus. IV. Structure elucidation of pyripyropenes M to R.

Six new pyripyropenes, M to R, were isolated from the ethyl acetate extracts of the jar fermentation broth of Aspergillus fumigatus FO-1289-2501. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to L. Among them pyripyropene M showed the most potent inhibition against acyl-CoA : cholesterol acyltransferase activity with an IC50 value of 3.80 microM in rat liver microsomes, but pyripyropenes N to R showed moderate inhibitory activity (IC50 11.0 approximately 78.0 microM).

Animals↗
PubMed1996

Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer.

UNLABELLED: We retrospectively investigated the value of PET with fluorine-18 fluorodeoxyglucose (FDG) for preoperative chemotherapy response in patients with locally advanced breast cancer. METHODS: FDG-PET studies were performed on 16 consecutive patients. All patients had PET studies before chemotherapy, 13 patients between the end of the first cycle and at the midpoint of chemotherapy, and 14 patients before surgery. Visual diagnoses and the standardized uptake values (SUV) of PET scans were compared with pathology findings at surgery and with the results of mammography, ultrasonography (US) or both, which were performed before chemotherapy and before local surgery for residual disease. Each patient's clinical course was monitored for up to 3 yr. RESULTS: Sensitivity for detection of pathologically proven primary lesions was 100%, 62.5% and 87.5% with FDG-PET, mammography and US, respectively; and sensitivity for detection of initial nodal involvement was 77%, 70% and 87.5%, respectively. Sensitivity for detection of residual primary tumor was 75%, 71.4% and 87.5%, respectively; and sensitivity for detection of residual nodal involvement was 41.6%, 71.4% and 66.6%, respectively. The mean SUV value of primary lesions was 9.4 (range 2.0-20.7, n = 16), with only two lesions showing an SUV below 3. Clinical improvement of primary lesions was seen in all patients; improvement with smaller size and less FDG uptake was visible as early as the second study in 11 patients (69%). Mean SUV values obtained at the second and third studies decreased significantly from those obtained in the first study. In four patients, the disease recurred after breast surgery with high SUV values. The mammograms and sonograms obtained before surgery showed a decrease in the diameter of 6 and 12 primary lesions of the 13 and 14 patients examined, respectively. CONCLUSION: FDG-PET is valuable for monitoring the effects of preoperative chemotherapy in patients with locally advanced breast cancer with better sensitivity for primary tumor and better specificity for nodal metastasis in comparison with ultrasonography.

Adult↗
PubMed1996

Patellar dislocation after total knee arthroplasty.

BACKGROUND: Patellar problem is an important cause of nonseptic failure of the current condylar design of total knee arthroplasties. Patellar dislocation after total knee arthroplasty is infrequent but can cause disabling symptoms. METHODS: From March, '84 to July, '92, 1652 total knee arthroplasties were performed at this Hospital. Of these 1100 knees in 978 patients were available to be followed up regularly at the Outpatient Department. Eleven cases of patellar dislocation after total knee arthroplasty were encountered during follow-up. Among these patients, nine patients had received operation at this Hospital; the other two patients had been referred here by the other hospitals. All 11 patients had been treated with surgical methods: proximal realignment of the quadriceps alone in 6 knees, lateral retinacular release combined with revision of the malaligned components in 2 knees, combined proximal and distal realignment in 2 knees and patellar tendon transfer in 1 knee. RESULTS: After an average follow-up of 21.8 months, from April, '84 to April, '93, there was one redislocation, unfortunately caused by trauma. Using the average knee rating scale of the Hospital for Special Surgery, New York, USA, the results of 90.5 were satisfactory and encouraging. CONCLUSIONS: Patellar dislocation after total knee arthroplasty can cause disabling symptoms, including pain, weakness, limited range of motion, extension lag and difficulty when climbing up or down stairs. The cause of patellar dislocation after total knee arthroplasty was error in surgical technique in this series. Revision of the component should be performed in those with malaligned component. Proximal realignment is recommended in those with quadriceps imbalance. Distal realignment is recommended only when proximal realignment alone has failed to restore proper patellar tracking, this should be carried out with great caution due to the potential for serious complications.

Aged↗
PubMed1996

Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors.

UNLABELLED: Two commonly used tumor-seeking agents for PET are 2-deoxy-2-18F-fluoro-D-glucose (FDG) and L-methyl-11C-methionine (Met). This study compared FDG and Met in detecting residual or recurrent malignant tumors in the same patients. METHODS: Thirty-four lesions in 24 patients with clinically suspected recurrent or residual tumors were studied with PET using Met as well as FDG. FDG scans were conducted 1 hr after the completion of PET with Met. The color-coded superimposed images of standardized uptake values (SUVs) and transmission data were produced, and the peak SUVs in the lesions were then evaluated. Lesions above 2.5 SUV were interpreted as positive results for active tumor. RESULTS: The sensitivity of FDG-PET and Met-PET were 64.5% (20/31 lesions) and 61.3% (19/31 lesions), respectively. The mean SUV of FDG in residual or recurrent malignant tumors (n = 31) was significantly higher than that of Met but there was a significant correlation (r = 0.788, p < 0.01) between FDG and Met SUVs in all lesions (n = 34). CONCLUSION: PET using FDG and Met appear equally effective in detecting residual or recurrent malignant tumors although FDG uptakes were slightly higher than Met uptakes. Both showed a limited diagnostic sensitivity for small (< 1.5 cm) tumors.

Adult↗
PubMed1996

Comparison of fluorine-18-FDG PET and technetium-99m-MIBI SPECT in evaluation of musculoskeletal sarcomas.

UNLABELLED: We compared the diagnostic accuracy of [18F]FDG PET and 99mTc-MIBI SPECT in musculoskeletal sarcomas. METHODS: Forty-eight patients with clinically suspected recurrent or residual musculoskeletal sarcomas were examined with both FDG-PET and MIBI-SPECT within 2 wk of each study (one follow-up study in nine patients and we follow-up studies in one patient). Imaging findings were visually inspected with grading scales in conjunction with CT and/or MRI, and count-density ratios of lesion-to-contralateral area and standard uptake values (SUVs) of FDG and MIBI in lesions were also generated. The results were correlated with histologic findings (in 51 studies) and/or long-term follow-up evaluations. RESULTS: The diagnostic sensitivities and specificities were 98% and 90% using FDG, and 81.6% and 80% using MIBI, respectively, with statistical significance in the sensitivity. The tumors were demonstrated better in FDG studies, which produced higher visual grades (2.1 versus 1.6), and the tumors showed increasing SUVs with time (from 6.3 to 7.3). Four of nine patients with positive FDG but negative MIBI scans failed to respond to multidrug therapy. CONCLUSION: FDG-PET and MIBI-SPECT are useful in differentiating active sarcomas from post-treatment changes and in evaluating therapeutic response. MIBI-SPECT and FDG-PET findings should be interpreted in con junction with CT and/or MRI. FDG-PET shows statistically significant higher sensitivity than MIBI-SPECT. A positive FDG but negative MIBI scan might suggest a multidrug resistance.

Adult↗