Biomedical subjects

Keigo Endo

Publications and source records attributed to Keigo Endo.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Design, synthesis, and evaluation of [188Re]organorhenium-labeled antibody fragments with renal enzyme-cleavable linkage for low renal radioactivity levels.

Renal localization of radiolabeled antibody fragments constitutes a problem in targeted imaging and radiotherapy. We have reported that Fab fragments labeled with 3'-[131I]iodohippuryl Nepsilon-maleoyl-lysine (HML) showed markedly low renal radioactivity levels even shortly after injection, due to a rapid and selective release of m-[131I]iodohippuric acid by the action of brush border enzymes. To estimate the applicability of the molecular design to metallic radionuclides, [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was conjugated with Nepsilon-tert-butoxycarbonyl-glycyl-lysine or Nepsilon-maleoyl-glycyl-lysine to prepare [188Re]CpTR-GK-Boc or [188Re]CpTR-GK. The cleavage of the glycyl-lysine linkage of the two compounds generates a glycine conjugate of [188Re]CpTR-COOH ([188Re]CpTR-Gly), which possesses in vivo behaviors similar to those of m-iodohippuric acid. The hydrolysis rate of the peptide bond in [188Re]CpTR-GK-Boc was compared with that in 3'-[125I]iodohippuryl Nepsilon-Boc-lysine ([125I]HL-Boc) using brush border membrane vesicles (BBMVs) prepared from rat kidneys. [188Re]CpTR-GK was conjugated to thiolated Fab fragments to prepare [188Re]CpTR-GK-Fab. The biodistribution of radioactivity after injection of [188Re]CpTR-GK-Fab was compared with that of [125I]HML-Fab and [188Re]CpTR-Fab prepared by conjugating N-hydroxysuccinimidyl ester of [188Re]CpTR-COOH with antibody fragments. While [188Re]CpTR-GK-Boc liberated [188Re]CpTR-Gly in BBMVs, [125I]HL-Boc liberated m-[125I]iodohippuric acid at a much faster rate. In addition, although [125I]HL-Boc was hydrolyzed by both metalloenzymes and nonmetalloenzymes, metalloenzymes were responsible for the cleavage of the peptide linkage in [188Re]CpTR-GK-Boc. In biodistribution studies, [188Re]CpTR-GK-Fab exhibited significantly lower renal radioactivity levels than did [188Re]CpTR-Fab. However, the renal radioactivity levels of [188Re]CpTR-GK-Fab were slightly higher than those of [125I]HML-Fab. The analysis of urine samples collected for 6 h postinjection of [188Re]CpTR-GK-Fab showed that [188Re]CpTR-Gly was the major radiometabolite. In tumor-bearing mice, [188Re]CpTR-GK-Fab significantly reduced renal radioactivity levels without impairing the radioactivity levels in tumor. These findings indicate that the molecular design of HML can be applied to metallic radionuclides by using a radiometal chelate of high inertness and by designing a radiometabolite of high urinary excretion when released from antibody fragments following cleavage of a glycyl-lysine linkage. This study also indicates that a change in chemical structure of a radiolabel attached to a glycyl-lysine linkage significantly affected enzymes involved in the hydrolysis reaction. Since there are many kinds of enzymes that cleave a variety of peptide linkages on the renal brush border membrane, selection of a peptide linkage optimal to a radiometal chelate of interest may provide radiolabeled antibody fragments that exhibit renal radioactivity levels similar to those of [131I]HML-labeled ones. The in vitro system using BBMVs might be useful for selecting an appropriate peptide linkage.

Animals↗

PubMedDate not supplied

Hypointensities in the brain on T2*-weighted gradient-echo magnetic resonance imaging.

The objectives of this review are to present various entities that can result in hypointensity on brain T2*-weighted gradient-echo (GE) images and to show the usefulness of this sequence. There are six etiologies, resulting in hypointensity on T2*-weighted GE images, ie, the presence of hemosiderin, deoxyhemogrobin, ferritin, calcium, other metals, and air. This sequence is sensitive to magnetic susceptibility effect and useful for detecting some kinds of small brain lesions and for differential diagnosis in some special conditions.

Brain↗

PubMedDate not supplied

Evaluation of hemangioma by positron emission tomography: role in a multimodality approach.

PURPOSE: The relative utility of various preoperative diagnostic imaging modalities for the evaluation of hemangioma of the extremities, including positron emission tomography (PET) (using 18F-fluoro-2-deoxy-D-glucose [FDG] and fluorine-18 alpha-methyltyrosine [FMT]), computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), was investigated. METHODS: Imaging findings in 16 patients with 16 histopathologically documented hemangiomas of the extremities were retrospectively reviewed. Preoperative imaging included: FDG-PET (n = 16), FMT-PET (n = 12), MRI (n =16), CT (n =11), and DSA (n =14). RESULTS: All 16 lesions examined by PET with FDG and/or FMT showed accumulation. The standardized uptake values (SUVs) for FDG-PET for the 16 examined tumors ranged from 0.7 to 1.67; for FMT-PET, they ranged from 0.14 to 1.00. The SUVs with both tracers indicated the benign nature of the tumor. Computed tomography demonstrated variable attenuation and phleboliths in two patients. The MRI signal characteristics were relatively consistent: heterogeneous signals were slightly higher than those of skeletal muscle on T1-weighted images and brighter than those of subcutaneous fat on T2-weighted images. The pooling and cotton-wool staining depicted in DSA was found to be significantly correlated with FDG accumulation, suggesting that localized blood retention-induced ischemia may accelerate anaerobic glycolysis, which leads to high FDG uptake. CONCLUSION: Although plain radiography, CT, MRI, and angiography may provide anatomic extent and be pathognomonic, FDG-PET and FMT-PET may be the most reliable among the studied imaging modalities for differentiating benign hemangiomas from other soft tissue tumors, especially malignant neoplasms.

Adolescent↗

PubMedDate not supplied

Carbon-11 choline positron emission tomography in musculoskeletal tumors: comparison with fluorine-18 fluorodeoxyglucose positron emission tomography.

PURPOSE: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET. METHOD: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET. RESULTS: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371). CONCLUSION: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.

Adolescent↗

PubMedDate not supplied

Correlation of 18-F-fluorodeoxyglucose (FDG) accumulation with glucose transporter (Glut-1) expression in esophageal squamous cell carcinoma.

BACKGROUND: We previously reported that positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) might be a useful tool for evaluating the stage of esophageal squamous cell carcinoma (SCC), and that FDG-PET shows greater accuracy in the diagnosis of lymph node metastasis than computed tomography. Further, we elucidated the relationships among FDG-PET performance, glucose transporter (Glut)-1 expression and serum levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA) and squamous cell carcinoma antigen (SCC-Ag) in esophageal SCC. PATIENTS AND METHODS: We studied 44 patients with thoracic esophageal SCC who had undergone radical esophagectomy. Immunohistochemical analysis was used to detect the expression of Glut-1 in resected specimens and FDG accumulation was assessed by FDG-PET scan. RESULTS: FDG uptake in the primary tumor was found in 34 out of 44 (77.3%) patients. No significant correlation was observed between SUVs and the tumor markers CEA, CYFRA and SCC-Ag. The survival rate in patients with high FDG uptake (SUV > 3) was significantly lower than in cases with low FDG uptake (SUV < 3) (p < 0.01). A significant correlation was observed between SUV and Glut-1 expression (p < 0.05). The prognosis in patients with both low Glut-1 expression and low FDG uptake tended to be more favorable than in patients with high Glut-1 expression and/or high FDG uptake. CONCLUSION: Glut-1 expression was related to FDG uptake, and assessment of both FDG uptake and Glut-1 expression might be useful for providing prognostic information in patients with esophageal SCC.

Adult↗

PubMedDate not supplied

The combination of multi-voxel MR spectroscopy with MR imaging improve the diagnostic accuracy for localization of prostate cancer.

BACKGROUND: We assessed the usefulness of combined multi-voxel magnetic resonance spectroscopy (MRS) and MR imaging (MRI) in the diagnosis of prostate cancer localization. PATIENTS AND METHODS: MRS and MRI were performed in 21 patients with prostate cancer. On T2-weighted images, tumor localization was based on low signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed when the ratio of choline plus creatine to citrate was greater than 0.86. The results were analyzed with reference to pathological confirmation of prostate cancer at bilateral or unilateral lobe. RESULTS: Six out of 11 patients with unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9 of 10 patients with bilateral positive biopsy specimens were diagnosed as bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and MRS. The accuracy of MRI alone was 71.4%, while that of combined MRI and MRS was 81.0%. CONCLUSION: Combined MRI and MRS improved the diagnostic accuracy for localization of prostate cancer.

Adenocarcinoma↗

PubMedDate not supplied

Comparison between whole-body positron emission tomography and bone scintigraphy in evaluating bony metastases of esophageal carcinomas.

BACKGROUND: Positron emission tomography (PET) with 18-F-fluorodeoxyglucose (FDG) has already proved useful in assessing the extension of esophageal carcinomas, detecting tumor recurrence and monitoring responses to therapy. This study aimed to elucidate the potential role of FDG-PET compared with technetium-99m methylene diphosphonate (Tc-99m MDP) bone scintigraphy in the evaluation of bony metastasis in esophageal carcinoma patients. PATIENTS AND METHODS: Forty-four patients with thoracic esophageal carcinomas, who underwent FDG-PET together with bone scintigraphy within 1 month between January 2000 and September 2003, were included in this study. RESULTS: Of the 44 patients, 13 had 31 bone metastases and, of these, 6 were diagnosed pretreatment and 7 had recurrence after esophagectomy surgery. Of the 31 metastases, 9 were in the vertebral column, 11 in the thoracic cage (including the ribs, clavicle, sternum and scapula), 9 in the pelvic bones and 2 in the long bones of the extremities. In evaluating the detection of bony metastasis, FDG-PET showed 92% sensitivity, 94% specificity and 93% accuracy, compared with 77%, 84% and 82%o, respectively, for bone scintigraphy. Although the sensitivity, specificity and accuracy of PET were slightly higher than those of bone scintigraphy, these differences were not statistically significant according to the McNemar's test. Three patients with false-negative findings on their bone scans had positive findings with PET; all of these lesions were osteolytic metastases. CONCLUSION: FDG-PET scans were superior to bone scintigraphy in detecting bony metastases of esophageal carcinomas. Therefore, FDG-PET can be used for the detection and follow-up of bone tumors when Tc-99m MDP bone scintigraphy gives negative findings.

Adult↗