Biomedical subjects

June-Key Chung

Publications and source records attributed to June-Key Chung.

72 records · Page 4Linked to original sources

PubMed2003

Prognostic value of rest (201)Tl-dipyridamole stress (99m)Tc-sestamibi gated SPECT for predicting patient-based clinical outcomes after bypass surgery in patients with ischemic left ventricular dysfunction.

UNLABELLED: We investigated the postoperative prognostic value of preoperative myocardial SPECT for predicting clinical outcomes, including event-free survival and functional improvement. METHODS: A total of 123 patients with ischemic heart disease and left ventricular dysfunction were enrolled. The ratio of men to women was 103:20, and the mean (+/-SD) age was 61 +/- 8 y. The disease involved 3 vessels in 95 patients, 2 vessels in 27 patients, and 1 vessel in 1 patient. Rest (201)Tl-dipyridamole stress (99m)Tc-sestamibi gated 24-h-delayed SPECT was performed before and 3-4 mo after bypass surgery. With a 20-segment model, a dysfunctional segment was defined as that with systolic wall thickening of <20%. Dysfunctional but viable segments were defined for each viability predictor, including rest thallium uptake of >60%, reversibility score (rest perfusion minus stress perfusion) of >7, systolic wall thickening of >10%, and 24-h-delayed thallium uptake of >60%. Global left ventricular functional improvement was defined as a 5% increase in the left ventricular ejection fraction (LVEF) or a 10-mL decrease in the end-systolic volume (ESV). A long-term follow-up evaluation was performed by chart reviews and telephone interviews over a period of up to 6 y. Cardiac events were defined as cardiac death, myocardial infarction, or heart failure requiring hospitalization. RESULTS: After bypass surgery, the LVEF was improved from 36.4% +/- 8.8% (mean +/- SD) to 44.3% +/- 11.1%, and the ESV was improved from 96.6 +/- 46.7 mL (mean +/- SD) to 75.1 +/- 44.0 mL. Global left ventricular function was improved in 96 patients but not improved in 27. Rest thallium uptake (>or=4 segments) and reversibility (>or=5 segments) were found to be significant variables in the receiver-operating-characteristic (ROC) curve analysis, with area-under-the-curve (AUC) values of 0.755 (P < 0.05) and 0.735 (P < 0.05), respectively. The values for preserved systolic wall thickening and delayed thallium uptake had no statistical significance. Using a multivariate logistic function, we created a single variable consisting of rest thallium uptake and reversibility; this variable had better prediction power than any other single variable (AUC value for the ROC curve, 0.794). Patients with a higher logistic function value (>or=0.84) showed better event-free survival than did those with a lower logistic function value (<0.84) (log-rank test, P < 0.05). CONCLUSION: The number of viable segments should be >4 for rest (201)Tl SPECT or >5 for the reversibility parameter for the prediction of global functional improvement in a patient-based evaluation. With a logistic function created from these parameters, the long-term clinical prognosis after bypass surgery could be predicted by the presence of viability on preoperative rest-stress myocardial SPECT.

Coronary Artery Bypass↗

PubMed2003

Lipiodol solution of 188Re-HDD as a new therapeutic agent for transhepatic arterial embolization in liver cancer: preclinical study in a rabbit liver cancer model.

UNLABELLED: It has been reported that lipiodol solution of (188)Re-labeled 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N(2)S(2) derivative, shows excellent targeting of liver cancer after transhepatic arterial embolization (TAE). However, its tumor retention is not high enough to treat liver cancer. Therefore, a new form of TDD, 4-hexadecyl-TDD (HDD), was developed to improve tumor retention by introducing a long alkyl chain. In this study, we compared the tumor retention properties of (188)Re-HDD/lipiodol and (188)Re-TDD/lipiodol, using a rabbit liver cancer model, and performed dosimetry using the results. METHODS: The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE was performed on 3 rabbits with (188)Re-TDD/lipiodol and on 4 rabbits with (188)Re-HDD/lipiodol, and conjugated anterior and posterior planar scans were obtained at 1, 2, 6, 24, and 48 h after TAE. From these images, tumor retention was calculated and compared between (188)Re-TDD and (188)Re-HDD. Afterward, the required dose of radioactivity and the radiation dosimetry for exposure of major organs were calculated using MIRDOSE3.1 software. RESULTS: The residence times of radioactivity in the liver were 10.2 +/- 1.0 h in the (188)Re-TDD group and 17.6 +/- 0.8 h in the (188)Re-HDD group (P = 0.034). The required radioactivity for 100 Gy of irradiation to 2.64- to 5.27-cm tumors was 142-1,070 MBq of (188)Re-HDD in the rabbit model. The radiation exposures for the major organs were within the tolerable range, and the S-value for the whole body (effective dose equivalent) was calculated to be 0.209 mSv/MBq. CONCLUSION: Introduction of a long alkyl chain significantly improved the tumor retention of (188)Re-HDD/lipiodol, compared with that of (188)Re-TDD/lipiodol. Moreover, the required radioactivity for humans and the radiation exposure were within the feasible range for clinical application.

Animals↗

PubMed2002

Criteria for definition of regional functional improvement on quantitative post-stress gated myocardial SPET after bypass surgery in patients with ischaemic cardiomyopathy.

Myocardial viability can be defined as functional improvement of dysfunctional myocardium after revascularization. The purpose of this study was to define the optimal criteria for definition of regional functional improvement after coronary artery bypass graft (CABG) surgery on quantitative gated single-photon emission tomography (SPET). Thirty-two patients (26 men, 6 women; age 56 +/- 13 years) with coronary artery disease (three-vessel disease, 17; two-vessel disease, 15; previous history of myocardial infarction, 9) and severe left ventricular dysfunction (LVEF < or = 35%) underwent CABG. Rest thallium-201/dipyridamole stress technetium-99m methoxyisobutylisonitrile gated myocardial SPET was performed before and 3 months after CABG. Global LV functional improvement was defined as either an improvement in LVEF of 10% ( n = 15) or an improvement in LVEF of 5% combined with a decrease in end-systolic volume of 10 ml ( n = 2) after CABG on quantitative gated SPET. Postoperative regional wall thickening improvement (DeltaRWT), regional wall motion improvement (DeltaRWM) and regional resting (DeltaRP) and stress perfusion improvement (DeltaRstrP) were used to determine global functional improvement by ROC curve analysis, and the optimal criteria for definition of viable regional dysfunctional myocardium were defined on the ROC curves. Correlations were verified by determining the number of improved myocardial regions and LVEF improvement. LVEF was improved from 25% +/- 6% to 34% +/- 11% after CABG. A total of 229 segments were dysfunctional (wall motion < or = 2 mm, thickening < or = 20%) before CABG. On ROC curve analysis using global functional improvement as an indicator of viability, the areas under the ROC curves (AUCs) of DeltaRWT and DeltaRWM were 0.717 and 0.620, respectively. The AUC of DeltaRWT was significantly larger than that of DeltaRWM ( P = 0.009) and the optimal cut-off value of DeltaRWT was 15%. The AUCs of DeltaRP and DeltaRstrP were not significant. The correlation coefficients between summed DeltaRWT and DeltaRWM and LVEF improvement were 0.591 and 0.472, respectively. The number of segments with a DeltaRWT of more than 15% correlated with LVEF improvement (rho = 0.533 by Spearman rank correlation). Regional wall thickening improvement showed the best correlation with global LV functional improvement after CABG. The most reliable regional criterion of myocardial viability was improvement in regional wall thickening by > or = 15% on quantitative gated SPET.

Cardiac Volume↗

PubMed2002

The usefulness of repeated ictal SPET for the localization of epileptogenic zones in intractable epilepsy.

This study investigated whether repeated ictal single-photon emission tomography (SPET) is helpful in the localization of epileptogenic zones and whether it can provide information confirming that an area of increased perfusion is really the culprit epileptogenic lesion. Fifty-four repeated ictal SPET studies were performed in 24 patients with ambiguous or unexpected findings on the first ictal SPET study. These patients were enrolled from among 502 patients with intractable epilepsy in whom pre-operative localization of epileptogenic zones was attempted with a view to possible surgical resection. Video monitoring of ictal behaviour and EEGs was performed in all patients. Repeated ictal SPET was performed using technetium-99m hexamethylpropylene amine oxime (HMPAO) when there was no prominently hyperperfused area or when unexpected findings were obtained during the first study. Two ictal SPET studies were performed in 19 patients, three studies in four patients and four studies in one patient. The average delay between ictal onset and injection was 28 s for the first study and 22 s for the second, third and fourth studies. Using interictal SPET, ictal-interictal subtraction images were acquired and co-registered with the population magnetic resonance imaging (MRI) template. Invasive study and surgery were performed in 18 patients, and in these cases the surgical outcome was known. In the other six patients, epileptogenic foci were determined using MRI, positron emission tomography (PET) and ictal EEG findings. Two patients were found to have mesial temporal lobe epilepsy, two lateral temporal lobe epilepsy, eight frontal lobe epilepsy, three parietal lobe epilepsy and one occipital lobe epilepsy. The other eight had multifocal epilepsy. The first study was normal in 12 patients (group I) and indicated certain zones to be epileptogenic in the other 12 (group II). Among group I, the correct epileptogenic zone or lateralization was revealed at the repeated study in nine patients, while in the other three it was not. Among group II, six patients showed the same results at the second study, thus confirming that the initially identified zones were of epileptogenic significance. In the other six patients, different areas were identified on the first and second studies, and repeated ictal SPET corroborated multifocality of the ictal EEG findings in five. These results indicate that repeated ictal SPET is useful because it can yield new or additional information about the epileptogenic zones and can confirm that a region of interest is an epileptogenic zone or that the epilepsy is of multifocal origin.

Adolescent↗

PubMed2002

Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET.

The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.

Brain Diseases↗

PubMed2002

In vitro and in vivo characteristics of a human colon cancer cell line, SNU-C5N, expressing sodium-iodide symporter.

Rat NIS (rNIS) genes were transfected into a human colon cancer cell line (SNU-C5) by lipofection. The transfected cells (SNU-C5N) exhibited an increase 125I uptake to a level 10 times higher than the untransfected SNU-C5 cells. The addition of 300 microM DIDS, an anion channel blocker, to the culture media led to a 2.35 times increase of 125I uptake in the cells. For the first 10 minutes, up to 70% of the cellular radioactivity was released into the medium. In the biodistribution study using SNU-C5N-xenografted mice, the %ID/g of the SNU-C5N tumors at 1, 3, 6, and 12 h after the 125I injection were 4.43%, 1.09%, 1.05%, and 0.05%, respectively, which were significantly higher than those for the SNU-C5 tumors (P<0.05). In tumor imaging, the SNU-C5N-xenografted tumor was clearly visible. In this study, NIS lipofection is efficient for triggering significant iodide uptake by a nonthyroidal tumor. However, for an increased therapeutic effect, the key issue is iodide retention in the target tissue.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2002

Cationic complex: (99m)Tc-N,N'-dimethyldiaminedithiol.

Diaminedithiol (DADT) or N-monosubstituted DADT is known to form lipophilic neutral chelates with technetium. As a result, they are used for brain imaging agents. However, 99mTc-N,N'-dimethylDADT has been demonstrated to have a positive charge and a lower lipophilicity (log P = 0.1) in this experiment. The results of a biodistribution study showed that most activity was found in the intestine after 1 hr, which is the evidence of bile excretion. Increased heart-uptake in mice suggests that this compound or its derivatives can be used as a myocardial-imaging agent.

Animals↗

PubMed2002

Identification of angiogenesis in primary breast carcinoma according to the image analysis.

Tumor angiogenesis may be an independent prognostic factor for breast cancer survival. However, we can get the angiogenic property of the breast cancer only after the removal of breast tissue. To get this information before surgical resection of the tumor, we evaluated 29 breast carcinoma patients with Tc-99m MIBI scintimammography and power Doppler ultrasound (US) with a microbubble contrast agent preoperatively and compare their results with intratumoral microvessel density (IMD) and reverse transcriptase-polymerase chain reaction (RT-PCR) of VEGF mRNA. IMD was well correlated with VEGF121 (r = 0.220, P = 0.024) and VEGF165 (r = 0.419, P = 0.046) mRNA level of the tumor. Power Doppler US grading of the tumor is well correlated with IMD (r = 0.552, P = 0.033). However, early uptake and washout index calculated from Tc-99m MIBI scintimammography showed no correlation with IMD or VEGF mRNA level, while washout index was inversely correlated with power Doppler US grading (r = -0.945, P = 0.001). In conclusion, the preoperative evaluation of breast cancer with power Doppler US with a microbubble contrast agent could predict tumor angiogenesis. Tc-99m MIBI scintimammography needs further study to use it as an image analysis for angiogenesis.

Adult↗

PubMed2002

Superiority of HMPAO ictal SPECT to ECD ictal SPECT in localizing the epileptogenic zone.

PURPOSE: We examined diagnostic performances of Tc-99m hexamethylpropylene amine oxime (HMPAO) and Tc-99m electron capture detection (ECD) ictal single-photon emission computed tomography (SPECT) to localize the epileptogenic zones in mesial temporal lobe epilepsy (TLE) and neocortical epilepsy (NE). METHODS: Epileptogenic zones were identified by invasive EEG or surgical outcome. Ictal SPECT was performed with stabilized Tc-99m HMPAO (TLE, 17; NE, 23) and with Tc-99m ECD (TLE, 7; NE, 7). Single-blind visual interpretation was used to localize the epileptogenic zones. Asymmetric index was calculated. Subtraction ictal SPECT was coregistered to a magnetic resonance imaging (MRI) template. RESULTS: In TLE, the sensitivity of Tc-99m HMPAO SPECT was 82% (14 of 17) and that of Tc-99m ECD SPECT was 71% (five of seven). The asymmetric index (AI; 25 +/- 10) of Tc-99m HMPAO SPECT was larger (p = 0.05) than the AI (13 +/- 13) of Tc-99m ECD SPECT in patients with TLE. In NE, the sensitivity of Tc-99m HMPAO SPECT was 70% (16 of 23), but that of Tc-99m ECD SPECT was 29% (two of seven). The AI (15 +/- 10) of Tc-99m HMPAO SPECT was significantly larger (p = 0.02) than the AI (4.8 +/- 6) of Tc-99m ECD SPECT in patients with NE. Subtraction ictal SPECT coregistered to MRI supported the visual assessment. CONCLUSIONS: We concluded that the sensitivity of Tc-99m ECD ictal SPECT is similar to that of Tc-99m HMPAO ictal SPECT in TLE; however, ictal hyperperfusion was higher with the Tc-99m HMPAO SPECT. In patients with NE, Tc-99m HMPAO ictal SPECT also was superior to Tc-99m ECD ictal SPECT in sensitivity and degree of hyperperfusion.

Adult↗

PubMed2002

Septal stunning by dipyridamole stress shown on quantitative gated perfusion SPECT in a child with hypertrophic cardiomyopathy.

PURPOSE: Myocardial ischemia is an important problem in hypertrophic cardiomyopathy. Stunning is an important mechanism in progressive dysfunction of the ischemic myocardium. In this report, the authors found prolonged myocardial stunning in a child with hypertrophic cardiomyopathy that was induced by dipyridamole stress on quantitative gated SPECT. MATERIALS AND METHODS: A 6-year-old boy with septal hypertrophy underwent rest and dipyridamole stress gated myocardial SPECT. Software was used to quantify automatically segmental perfusion and function at rest and after stress. RESULTS: Perfusion imaging showed a reversible perfusion decrease in the hypertrophic septum. Cine-gated imaging of the septum showed dyskinesia and a severe abnormality of systolic thickening during the poststress period, whereas it showed nearly complete recovery at rest. Quantified regional perfusion and function indices also showed this perfusion decrease and myocardial dysfunction after dipyridamole stress. CONCLUSION: In a child with hypertrophic cardiomyopathy, myocardial stunning was induced by dipyridamole stress, in accordance with decreased perfusion reserve.

Cardiomyopathy, Hypertrophic↗

PubMed2002

(18)F-FDG PET in localization of frontal lobe epilepsy: comparison of visual and SPM analysis.

UNLABELLED: The sensitivity of (18)F-FDG PET to localize epileptogenic zones in frontal lobe epilepsy was evaluated by both visual assessment and statistical parametric mapping (SPM). METHODS: Twenty-nine patients with frontal lobe epilepsy were examined. All patients showed good outcome after surgical resection (Engel class I or II). On pathologic examination, 22 patients had cortical dysplasia, 4 had tumors, 1 had cortical scars, and 2 had an old infarct. Hypometabolic lesions were found on (18)F-FDG PET images by both visual assessment and SPM analysis. On SPM analysis, the cutoff threshold was varied and sensitivity to find epileptogenic zones was compared. RESULTS: MRI showed structural lesions in 15 patients and normal findings in 14. (18)F-FDG PET correctly localized the epileptogenic zones in 16 patients (55%) by visual assessment. The sensitivity of (18)F-FDG PET was 36% in patients without structural lesions on MRI and 73% in patients with structural lesions. On SPM analysis, using an uncorrected probability value of 0.005 as the threshold, the sensitivity of SPM analysis was 66%, which was not statistically different from the sensitivity of visual assessment. The sensitivity decreased according to the decrease in probability value. CONCLUSION: (18)F-FDG PET was sensitive in localizing epileptogenic zones by revealing hypometabolic areas in nonlesional patients with frontal lobe epilepsy as well as in lesional patients. SPM analysis showed a comparable sensitivity to visual assessment and could be used as an aid in diagnosing epileptogenic zones in frontal lobe epilepsy.

Adult↗

PubMed2002

Sodium iodide symporter: its role in nuclear medicine.

Thyroid iodide uptake is basic to the clinical applications of radioiodine. Iodide uptake occurs across the membrane of the thyroid follicular cells through an active transporter process mediated by the sodium iodide symporter (NIS). The recent cloning of the NIS gene enabled the better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to the clarification and expansion of its role in nuclear medicine. In papillary and follicular carcinoma, NIS immunostaining was positive in only a few tumor cells, and no NIS protein expression was detected in anaplastic carcinomas. Decreased NIS expression levels account for the reduced iodide uptake in thyroid carcinomas. Thus, by targeting NIS expression in cancer cells, we could enable these cells to concentrate iodide from plasma and in so doing offer the possibility of radioiodine therapy. Several investigators have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake by up to several hundredfold that of controls in nonthyroid cancers as well as in thyroid cancer. In addition, my group proposes that NIS may serve as an alternative imaging reporter gene in addition to the HSVtk and dopaminergic receptor genes. The NIS has the potential to expand the role of nuclear medicine in the future, just as it has served as the base for the development of nuclear medicine in the past.

Animals↗

PubMed2002

Usefulness of whole-body (18)F-FDG PET in patients with suspected metastatic brain tumors.

UNLABELLED: The aim of this study was to evaluate the diagnostic value of whole-body (18)F-FDG PET imaging in the differentiation of metastatic brain tumor from primary brain tumor and in the localization of the primary lesion in patients with metastatic brain tumor. METHODS: The subjects consisted of 127 patients (77 men, 50 women; mean age +/- SD, 55 +/- 12 y) with brain masses that were suspected to be metastatic brain tumors on radiologic studies: 77 with confirmed metastatic brain tumor and 50 with primary brain tumor. Whole-body (18)F-FDG PET was performed on all patients. When the abnormal lesion was detected outside the brain, we interpreted the brain lesion as metastatic brain tumor. RESULTS: In 61 of the 77 patients with metastatic brain tumor, primary lesions were detected using whole-body (18)F-FDG PET. Of the remaining 16 patients (all false-negative cases), 7 were classified as metastases of unknown origin. In 47 of the 50 patients with primary brain tumor, whole-body (18)F-FDG PET did not show any other abnormal lesions. The sensitivity, specificity, positive and negative predictive values, and accuracy of PET for the detection of primary origin were 79.2%, 94.0%, 95.3%, 74.6%, and 85.0%, respectively. The most common primary origin of metastatic brain tumors on PET examination was lung cancer (48/61, 78.7%). The concordance rate between (18)F-FDG PET and conventional radiologic work-up was 80% in identifying primary lesion. Unknown bone or bone marrow metastases and unsuspected distant metastases were found in 14 patients (18%) and 24 patients (31%), respectively, on PET examination. CONCLUSION: Screening the patients with suspected metastatic brain tumors using whole-body (18)F-FDG PET could be helpful in differentiating metastatic brain tumor from primary brain tumor and in detecting the primary lesion.

Brain Neoplasms↗

PubMedDate not supplied

99mTc-neolactosylated human serum albumin for imaging the hepatic asialoglycoprotein receptor.

99mTc-labeled diethylenetriaminepentaacetic acid (DTPA)-coupled neogalactosyl human serum albumin (GSA) is used as an imaging agent for asialoglycoprotein receptor of the liver. However, its labeling is inconvenient because it should be incubated for 30 min at 50 degrees C. In addition, the conjugated DTPAs can cause decrease of pI and denaturation of protein. Therefore, we developed an improved agent 99mTc-neolactosyl human serum albumin (LSA) which contains a terminal galactose. LSA was synthesized by conjugating lactose to human serum albumin by the formation of a Schiff's base and successive reduction with sodium cyanoborohydride. The number of conjugated lactose molecules per LSA was 40.7 +/- 12.3. To simplify the labeling procedure, we used a direct labeling method that adopts a high affinity 99mTc binding site concept in antibody labeling. The produced LSA was reduced by beta-mercaptoethanol to generate sulfhydryl groups and purified by PD-10 size-exclusion column. The number of generated sulfhydryl groups per LSA was 21.9 +/- 3.0. Medronate and stannous chloride were added to the reduced LSA and freeze-dried. Finally, 99mTc-pertechnetate (37 MBq, 1 mL) was added to the vial and incubated for 10 min at room temperature. The labeling efficiency of 99mTc-LSA was higher than 98%, and the stability in human serum at 37 degrees C for 24 h was over 90%. Biodistribution study using balb/c mice and imaging study using SD rats showed high initial liver uptake and slow increase in the intestine due to hepatobiliary excretion after metabolism in the hepatocytes. Negligible spleen uptake was found while 99mTc-tin colloid showed significant amount of spleen uptake due to reticuloendothelial uptake. In conclusion, an improved agent, 99mTc-LSA, for imaging asialoglycoprotein receptor of the liver was successfully developed which showed a simple labeling procedure, high labeling efficiency, high stability, and high initial liver uptake.

Animals↗

PubMedDate not supplied

Preparation of 18F-human serum albumin: a simple and efficient protein labeling method with 18F using a hydrazone-formation method.

18F-labeling of proteins and peptides is important for positron emission tomography (PET). Although there are many methods for the labeling of proteins with (18)F, most of these are characterized by complicated procedures or low yields. Here, we report a novel and simple method which includes the preparation of [18F]fluorobenzaldehyde ([18F]FBA) and successive conjugation with hydrazinonicotinic acid-human serum albumin conjugate (HYNIC-HSA) via hydrazone formation. HYNIC-HSA, which can also be used for labeling with (99m)Tc, was prepared via reaction with N-hydroxysuccinimide (NHS) or tetrafluorophenyl (TFP) esters of HYNIC with HSA. No-carrier-added [18F]FBA was prepared by the nucleophilic substitution of [18F]fluoride to 4-trimethylammonium benzaldehyde triflate in the presence of tetrabutylammonium bicarbonate. [18F]FBA was purified by passing ion exchange cartridges (IC-H and QMA) and was adsorbed to a C18 Sep-Pak cartridge. The adsorbed [18F]FBA was then eluted with 50% ethanol. HYNIC-HSA was added to the solution and conjugated with [18F]FBA via hydrazone formation. 18F-HSA was purified with a PD10 column. Biodistribution of 18F-HSA, (99m)Tc-HSA, and [18F]FBA in mice were investigated at 10, 20, and 60 min after intravenous injection. The number of conjugated HYNIC molecules per HSA ranged from 5.2 to 23.2 depending on the reaction conditions. The labeling efficiency of 18F-FBA was 67 +/- 15.7%. The radiochemical purity after purification was over 99%. The conjugation efficiency of HYNIC-HSA with [18F]FBA was between 25% and 90%. The conjugation efficiency was observed to increase with increases in the number of conjugated HYNIC, the HYNIC-HSA concentration, or temperature. 18F-HSA exhibited a biodistribution pattern similar to that of (99m)Tc-HSA while [18F]FBA showed much lower blood activity than that of 18F-HSA and (99m)Tc-HSA. We concluded that 18F-HSA was successfully labeled using a novel method which involves hydrazone formation between [18F]FBA and HYNIC-HSA. This method can be applied to the 18F-labeling of other proteins or peptides.

Animals↗

PubMedDate not supplied

Consideration of perfusion reserve in viability assessment by myocardial Tl-201 rest-redistribution SPECT: a quantitative study with dual-isotope SPECT.

BACKGROUND: To optimize the use of thallium 201 rest-redistribution study in Tl-201/technetium 99m sestamibi dual-isotope single photon emission computed tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable myocardium was examined according to the degree of perfusion reserve. METHODS AND RESULTS: Twenty patients with both unstable angina and left ventricular dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after coronary artery bypass grafting. Through use of a 20-segment model, segmental stress perfusion, rest perfusion, and systolic thickening were quantified on gated SPECT by means of automatic quantitation software. Perfusion was expressed as the average percentage of maximal radioactivity uptake. To represent perfusion reserve, the perfusion difference score (PDS) was defined as rest perfusion minus stress perfusion. A low PDS indicated little or no inducible ischemia, and a high PDS indicated inducible ischemia. In dysfunctional myocardium, viability was defined by the improvement of thickening after coronary artery bypass grafting. The overall predictability of Tl-201 redistribution for viability was 0.709 of the area under the curve (AUC) in receiver operating characteristic analysis. With a cutoff of 7, predictability was significantly better in the low PDS group (AUC = 0.785) than in the high PDS group (AUC = 0.582). CONCLUSIONS: The predictability of Tl-201 rest-redistribution for viability differs according to perfusion reserve. It was more reliable for dysfunctional myocardium with persistent perfusion decrease. On the basis of the continuum hypothesis of chronic stunning and hibernation, we suggest that dysfunctional myocardium with persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT.

Aged↗

PubMedDate not supplied

Comparison of the cost-effectiveness of stress myocardial SPECT and stress echocardiography in suspected coronary artery disease considering the prognostic value of false-negative results.

BACKGROUND: The prognoses of patients with false-negative test results by myocardial single photon emission computed tomography (SPECT) and by stress echocardiography are known to be different; the prognosis with false-negative SPECT is better in suspected and proven coronary artery disease (CAD). METHODS AND RESULTS: Three strategies by which to diagnose CAD were compared for their cost-effectiveness when considering the prognostic value of false-negative results: (1) stress myocardial SPECT by dipyridamole or adenosine followed by coronary angiography (CAG), (2) exercise stress echocardiography followed by CAG, and (3) dobutamine stress echocardiography followed by CAG. Delta quality-adjusted life-year (QALY) was calculated for the three strategies separately when annual mortality and infarction rates were 0.5% and 0.5% for myocardial SPECT and 2% and 2% for stress echocardiography, respectively. Costs were estimated and costs per DeltaQALY were calculated according to the pretest likelihood of CAD (pCAD). The myocardial SPECT followed by CAG strategy was the most cost-effective in the patients with a pCAD of 0.3 or greater, and the dobutamine echocardiography followed by CAG strategy was the most cost-effective in patients with a pCAD of 0.2 or lower. This was the case when we assumed that the nondiagnostic test rate of dobutamine echocardiography was 9% (in contrast to 0% by myocardial SPECT and 18% by exercise echocardiography). Sensitivity analysis showed that the cost-effectiveness of dobutamine echocardiography followed by CAG was best only if the prognosis of false-negative results of dobutamine echocardiography was better. The cost-effectiveness of exercise echocardiography was dubious because of the high nondiagnostic rate with inadequate exercise. CONCLUSIONS: When the lower event rates of (false) negative SPECT were considered, the relatively expensive myocardial SPECT strategy was more cost-effective than the cheaper stress echocardiography strategy in patients with a pCAD of 0.3 or greater. According to sensitivity analysis, the prognostic value of false-negative results and the nondiagnostic test rate were important determinants of stress myocardial study cost-effectiveness.

Coronary Angiography↗

PubMedDate not supplied

False positive and false negative FDG-PET scans in various thoracic diseases.

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is being used more and more to differentiate benign from malignant focal lesions and it has been shown to be more efficacious than conventional chest computed tomography (CT). However, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. Infectious diseases (mycobacterial, fungal, bacterial infection), sarcoidosis, radiation pneumonitis and post-operative surgical conditions have shown intense uptake on PET scan. On the other hand, tumors with low glycolytic activity such as adenomas, bronchioloalveolar carcinomas, carcinoid tumors, low grade lymphomas and small sized tumors have revealed false negative findings on PET scan. Furthermore, in diseases located near the physiologic uptake sites (heart, bladder, kidney, and liver), FDG-PET should be complemented with other imaging modalities to confirm results and to minimize false negative findings. Familiarity with these false positive and negative findings will help radiologists interpret PET scans more accurately and also will help to determine the significance of the findings. In this review, we illustrate false positive and negative findings of PET scan in a variety of diseases.

Cryptococcosis↗