Total Lesion Glycolysis Using 18F-FDG PET/CT as a Prognostic Factor for Locally Advanced Esophageal Cancer

Standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) have been considered prognostic factors for survival in many cancers. However, their prognostic value for radiotherapy-treated squamous esophageal cancer has not been evaluated. In this study, SUV, MTV, and TLG were measured to predict their prognostic role in overall survival (OS) in 38 esophageal cancer patients who had undergone 18F-FDG PET/CT before radiotherapy. TLG demonstrated higher sensitivity and specificity for predicting OS than MTV and SUV; and a better OS was observed in patients with low TLG compared to those with high TLG in locally advanced disease (OS, 46.9 months; 95% confidence interval [CI], 33.50-60.26 vs. 25.3 months; 95% CI, 8.37-42.28; P=0.003). Multivariate analyses in these patients determined that TLG and the use of combination chemotherapy were the independent prognostic factors for OS (hazard ratio [HR], 7.12; 95% CI, 2.038-24.857; P=0.002 and HR, 6.76; 95% CI, 2.149-21.248; P=0.001, respectively). These results suggest that TLG is an independent prognostic factor for OS and a better predictor of survival than MTV and SUV in patients with locally advanced esophageal cancer treated with radiotherapy.

Radiological Justification for and Optimization of Nuclear Medicine Practices in Korea

Nuclear medicine is a rapidly growing discipline that employs advanced novel hybrid techniques that provide unique anatomical and functional information, as well as targets for molecular therapy. Concomitantly, there has been an increase in the attention paid to medical radiation exposure. A radiological justification for the practice of nuclear medicine has been implemented mainly through referral guidelines based on research results such as prospective randomized clinical trials. The International Commission on Radiological Protection recommends diagnostic reference levels as a practical mechanism to optimize medical radiation exposure in order to be commensurate with the medical purpose. The Korean Society of Nuclear Medicine has been implementing radiological optimization through a survey of the protocols on how each hospital determines the dose of administration of each radiopharmaceutical. In the case of nuclear medicine, radiation exposure of caregivers and comforters of patients discharged after administration of therapeutic radiopharmaceuticals can occur; therefore, optimization has been implemented through written instructions for patients, based on international recommendations. The development of patient-radiation-dose monitoring software, and a national registry and management system of patient-radiation-dose is needed to implement radiological optimization through diagnostic reference levels. This management system must work in agreement with the "Institute for Quality Management of Nuclear Medicine", and must take into account the medical reality of Korea, such as low medicine fee, in order to implement reasonable radiological justification and optimization.

Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG-PET in Patients with Essential Tremor According to Their Response to Beta-Blockers

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.

Primary Pulmonary Low-Grade Angiosarcoma Characterized by Mismatch between 18F-FDG PET and Dynamic Contrast-Enhanced CT

We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an 18F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.

18F-FDG Positron-Emission Tomography/Computed Tomography Findings of Radiographic Lesions Suggesting Old Healed Tuberculosis

The presence of radiographic lesions suggesting old healed tuberculosis (TB) is one of the strongest risk factors for the subsequent development of active TB. We elucidated the metabolic activity of radiographic lesions suggesting old healed TB using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This cross-sectional study included 63 participants with radiographic lesions suggesting old healed TB and with available 18F-FDG PET/CT scans. The maximum standardized uptake value (SUVmax) measured in the lesions, the clinical characteristics, results of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) were analyzed. The SUVmax in old healed TB was 1.5 or higher among nine (14.3%) participants. Age (adjusted odds ratio [aOR], 1.23; 95% CI, 1.03-1.46), history of previous TB (aOR, 60.43; 95% CI, 1.71-2131.65), and extent of the lesions (aOR, 1.34; 95% CI, 1.02-1.75) were associated with higher SUVmax. The positive rates for the TST and IGRA were not different between groups with and without increased FDG uptake. Increased FDG uptake on 18F-FDG PET/CT was observed in a subset of patients with radiographic lesions suggesting old healed TB. Given that the factors associated with increased FDG uptake are known risk factors for TB development, the possibility exists that participants with old healed TB lesions with higher SUV on 18F-FDG PET/CT scans might be at higher risk for active TB.

Comparison of two peptide radiotracers for prostate carcinoma targeting

OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95 percent. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32 percent of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

Usefulness of 18F-fluoro-2-deoxyglucose Positron Emission Tomography in Evaluation of Gastric Cancer Stage / 대한소화기학회지

BACKGROUND/AIMS: The usefulness of 18F-fluoro-2-deoxyglucose (FDG)-PET in detecting primary cancer, lymph node metastasis, and distant metastasis were studied in the gastric cancer patients. METHODS: The subjects were 392 gastric cancer patients who received FDG-PET and an abdominal CT test prior to surgery. The results of FDG-PET and CT were compared with the surgical and pathologic results. RESULTS: The primary site detection rate of FDG-PET was 74.4%, 50.3% in early gastric cancer and 92.0% in advanced gastric cancer. Detection rate was higher when tumors were larger than 3.5 cm, had deeper depth of invasion, and at a later stage (p or =T2), and lymph node metastasis were statistically significant factors in primary site detection rate. The sensitivity, specificity, and positive predictive value of FDG-PET to lymph node metastasis were 59.6%, 88.8%, and 81.1% respectively, sensitivity being lower compared to CT while specificity and positive predictive value were higher. Sensitivity, specificity, and positive predictive value to distant metastasis were, respectively, 66.7%, 99.2%, and 88.0%, similar to CT. In 21 of the 392 patients (5.4%), synchronous double primary cancers were detected. CONCLUSIONS: In gastric cancer, usefullness of FDG-PET is limited to the advanced stage. Diagnostic value of this test was not superior to CT. However, FDG-PET may be useful in detecting synchronous double primary cancers.

Effectiveness of 124I-PET/CT and 18F-FDG-PET/CT for Localizing Recurrence in Patients with Differentiated Thyroid Carcinoma

Although the prognosis of patients with differentiated thyroid carcinoma (DTC) is generally encouraging, a diagnostic dilemma is posed when an increasing level of serum thyroglobulin (Tg) is noted, without detection of a recurrent tumor using conventional imaging tools such as the iodine-131 whole-body scanning (the [131I] scan) or neck ultrasonography (US). The objective of the present study was to evaluate the diagnostic value of [124I]-PET/CT and [18F]-FDG-PET/CT in terms of accurate detection of both iodine- and non-iodine-avid recurrence, compared with that of conventional imaging such as the [131I] scan or neck ultrasonography (US). Between July 2009 and June 2010, we prospectively studied 19 DTC patients with elevated thyroglobulin levels but who do not show pathological lesions when conventional imaging modalities are used. All involved patients had undergone total thyroidectomy and radioiodine (RI) treatment, and who had been followed-up for a mean of 13 months (range, 6-21 months) after the last RI session. Combined [18F]-FDG-PET/CT and [124I]-PET/CT data were evaluated for detecting recurrent DTC lesions in study patients and compared with those of other radiological and/or cytological investigations. Nine of 19 patients (47.4%) showed pathological [18F]-FDG (5/19, 26.3%) or [124I]-PET (4/19, 21.1%) uptake, and were classed as true-positives. Among such patients, disease management was modified in six (66.7%) and disease was restaged in seven (77.8%). In particular, the use of the described imaging combination optimized planning of surgical resection to deal with locoregional recurrence in 21.1% (4/19) of patients, who were shown to be disease-free during follow-up after surgery. Our results indicate that combination of [18F]-FDG-PET/CT and [124I]-PET/CT affords a valuable diagnostic method that can be used to make therapeutic decisions in patients with DTC who are tumor-free on conventional imaging studies but who have high Tg levels.

Targetry for cyclotron production of no carrier-added cadmium- 109 from natAg[p, n] 109 Cd reaction

Solid targets that consist of powder and electrodeposited targets are used commonly to produce radionuclides by accelerators. Since silver is easily electrodeposited in cyanide baths and has a very excellent thermal conductivity, the electrodeposited target is preferable to produce [109] Cd. To avoid cracking of peeling of the target during bombardment, it should have a level surface and a good adhesion to substrate. Hence, suitable targetry has extraordinary importance for the interested radionuclide production. Excitation function of cadmium-109 via [nat] Ag [p,n][109] Cd reaction was investigated by using ALICE-91 code. The required thickness of the silver deposit was calculated by SRIM code. Theoretical yield was calculated by means of Simpson numerical integral method. Silver was electrodeposited on copper backing by the cyanide bath. The prepared targets were examined with morphology and thermal shock tests. The most favorable beam energy was determined as 15 MeV. The desired thickness was determined to be up to 48 micro m; the theoretical calculated yield was 2.69 micro Ci/ micro A.h. Scanning electron microscope [SEM] potomicrographs and thermal shock tests represented excellent quality of the electrodeposited target. The present study suggested a good potentiality of cadmium-109 production by induced proton on electrodeposited silver targets

Production of Ga-66 from natural zinc

In this study, production of Gallium-66 by irradiation of natural zinc target with 15 MeV protons was verified.Gallium-66 is an intermediate-lived radioisotope that has potential for positron emission tomography (PET), along study of the biological processes with intermediate to slow target tissue uptake. 66Ga [t1/2 = 9.49 h; ß+ (56.5 percent), EC(43.5 percent)] can be used in a large number of labeled proteins, peptides, and small molecules. We have produced 66Ga by irradiation of natural Zinc with 15 MeV proton beam, using the cyclotron -30Cyclon- at nuclear research center for agriculture and medicine. A 400µm Zinc target with copper backing substrate was irradiated for 1.5 hours with total integrated current 250µAh. Gallium has been purified from irradiated targets by passing through the cation exchange column and diisopropyl ether extraction. The concentration of zinc and copper in 0.1 and 0.5 ppm were respectively measured by polarography. In order to detect impurities, gallium radioisotopes were detected by a Canberra HPGe gamma spectrometer. The production yield at EOB was 7mCi/µAh with total activity of 1.75 Ci for Gallium-66. The ratio of activity at 9 hours after the EOB for 66Ga(t 1/2=9.5h), 68Ga(t1/2=1.1h) and 67Ga(t1/2=78h) was 98.63 percent, 1.12 percent and 0.25 percent respectively. The amount of 64Ga(t1/2=0.04h), and 70Ga(t1/2=0.35h) was not detectable. Due to using natural zinc, this method could be considered as an inexpensive method for laboratories studies. The production process comparing the irradiation of natural copper has no impurity such as copper-61, 64 and 67. The purification including cation-exchange and ether extraction afforded high yield beside negligible concentrations of copper and stable zinc as chemical impurity.

Factors affecting chemistry of reduction-mediated 99mTc-labelling of monoclonal antibodies and polyclonal human immunoglobulins.

In developing a new method for preparing a radiopharmaceutical for clinical investigation, a thorough understanding of reaction stoichiometry is crucial in optimizing the labelling chemistry. Factors determining labelling efficiency of the 2-mercaptoethanol (2-ME)-mediated 99mTc-labelling of antibody molecules were elucidated using anti-tumor monoclonal antibodies of different IgG subclasses (i.e. IOR-CEA(IgG1), M170(IgG1), 3F8(IgG3) and EMD (IgG2a)) and polyclonal human immunoglobulins (Sandoglobulin). Antibodies which were sensitive to 2-ME reduction (i.e. required 500-1000 molar excess of 2-ME) could tag 99mTc with high efficiency since they possessed abundant reactive sites (i.e. sulfydryl groups) for 99mTc binding. Reduction sensitivity of antibodies was unlikely to be affected by IgG subclass and could be rated as follows: Sandoglobulin > IOR-CEA > 3F8 > M170 > EMD. Concentrations of the reduced antibodies for effective labelling appeared to be related to the reduction sensitivity, i.e. 0.2, 0.4 and 0.6 mg/ml were required for labelling of IOR-CEA, 3F8 and M170 respectively. In addition, susceptibility to 2-ME reduction seemed to reflect the rate of antibody labelling. For 2-ME resistant molecules, i.e. M170 and EMD, successful labelling could be achieved by using a slow 99mTc reducing agent such as SnCl2 instead of SnF2 which reacted more rapidly. Since 2-ME generates reactive sulfhydryl groups that are distal to antigen binding sites, the immunoreactivity of the modified antibody was not affected by the effect of reduction.