Evaluation of Therapeutic Effects of Cognitive-Behavioral Therapy in Patients with Panic Disorder using Serial (99m)Tc-ECD Brain Perfusion / 핵의학분자영상

PURPOSE: Although several neuroanatomical models of panic disorder have been proposed, little is known regarding the neurological mechanisms underlying cognitive-behavioral therapy (CBT) in patients with panic disorder. This study was performed to identify the brain structures that show changes of regnioal cerebral blood flow (rCBF) after CBT in patients with panic disorder. MATERIALS AND METHODS: Seven patients who were diagnosed as panic disorder by DSM-IV were treated with CBT for 8 weeks and twelve healthy volunteers joined in this study. Serial (99m)Tc-ECD brain perfusion SPECT images were acquisited and PDSS-SR (Self-Report version of Panic Disorder Severity Scale) and ACQ (Agoraphobic Cognitive Question) scores were measured just before and after CBT in all patients. Data were analyzed using SPM2. RESULTS: Subjective symptoms were improved, and PDSS-SR and ACQ scores were significantly reduced (14.9+/-3.9 vs. 7.0+/-1.8, p<0.05; 30.3+/-8.5 vs. 21.6+/-3.4, p<0.05, respectively) after CBT in panic patients. Before CBT, a significant increase of rCBF was found in the cingulate gylus, thalamus, midbrain, both medial frontal and temporal lobes of the panic patients compared to the normal volunteers. After CBT, we observed a significant rCBF decrease in the left parahippocamus, right insula and cingulate gyrus, both frontal and temporal lobes, and a significant rCBF increase in both the occipital lobes, left insula, both frontal and left parietal lobes. CONCLUSION: These data suggested that CBT is effective for panic disorder and diminish the activity of the brain areas associated with fear in panic disorder.

Migration of 99mTc-Hexamethylpropylene Amine Oxime (HMPAO) Labeled Immature and Mature Dendritic Cells in the Mouse / 대한핵의학회잡지

PURPOSE: The purpose of this study is to evaluate migration of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labeled immature and mature dendritic cells (DC) in the mouse. METHODS: DC were collected from bone marrow (BM) of tibiae and femurs of mice. Immature and mature DC from BM cells were radiolabeled with 99mTc-HMPAO. To evaluate the functional and phenotypic changes of DC from radiolabeling, the allogeneic mixed lymphocyte reaction (MLR) and fluorescence-activated cell sorting (FACS) analysis were performed before and after labeling with 99mTc-HMPAO. Migration of intravenously injected DC (iv-DC) was assessed by serial gamma camera images of mice with or without subcutaneous tumor. Percent injected dose per gram (%ID/g) was calculated in lungs, liver, spleen, kidneys, and tumor through dissection of each mice after 24 hours of injection. RESULTS: Labeling efficiency of immature and mature DC were 60.4 +/- 5.4% and 61.8 +/- 6.7%, respectively. Iv-DC initially appeared in the lungs, then redistributed mainly to liver and spleen. Migration of mature DC to spleen was significantly higher than that of immature DC (38.3 +/- 4.0 % vs. 32.2 +/- 4.1 % in control group, 40.4 +/- 4.1% vs. 35.9 +/- 3.8 % in tumor group; p< 0.05). Migration to tumor was also significantly higher in mature DC than in immature DC (2.4 +/- 0.3% vs 1.7 +/- 0.2%; p=0.034). CONCLUSION: Assessment of migration pattern of DC in mice was possible using 99mTc-HMPAO labeled immature and mature DC. Migration of mature DC to spleen and tumor was higher than that of immature DC when they were i.v. injected.

A New Porcine Model of Ischemic Heart Failure and Pathologic Findings by Intra-Coronary Injection of Ethanol

BACKGROUND AND OBJECTIVE: A new porcine model of acute myocardial infarction (AMI), ischemic heart failure and pathologic findings of coronary artery by a transcatheter intracoronary ethyl alcohol injection has been developed. MATERIALS AND METHODS: Twelve female pigs underwent a transcatheter injection in the left anterior descending artery (LAD), using alcohol, to produce an apicoanteriorseptal AMI. Low pressure ballooning using a 2.5 mm over-the-wire balloon, just above the second and first diagonal branches, followed by a 1 mL injection of 99.9% ethyl alcohol was administered to 8 and 4 pigs, respectively. Follow-up coronary and left ventricular (LV) angiograms and echocardiography were performed 4 weeks after the alcohol injection. Myocardial SPECT using 201Tl (and 99mTc-MIBI) and triphenyl tetrazolium chloride (TTC) stain were performed after sacrifice. The quantity of TTC stain and amount of 201Thallium uptake were compared using the Vision Workstation. The histopathological findings of the infarcted myocardium and coronary artery were demonstrated after 28 days. RESULTS: Procedure-related mortality was observed in two-pigs of the proximal LAD injection group. Four pigs suffered from ventricular tachycardia, which was converted into sinus rhythm by dc cardioversion. The four-week follow-up coronary angiography revealed persistently occluded LAD in all pigs. The LV angiogram showed akinetic movement in the apicoanteriorseptal wall with an ejection fraction of 46.5+/-3.3%. Myocardial SPECT revealed a perfusion defect in the apicoanterior wall of all pigs. The percentage area of perfusion defect was 22.2+/-3.06%. The TTC did not stain the myocardium in the apicoanterior wall. The percentage of non-stained myocardium was 23.5+/-2.70%. A histological examination revealed severe fibrosis in the infarcted myocardium and massive thrombus, with organization and calcification. CONCLUSION: The porcine model of acute myocardial infarction using an intracoronary ethanol injection into the distal LAD is safe, reliable and reproducible, and can be used for future research into myocardial regeneration and ischemic LV failure.

Intratumoral Injection of (188)Re labeled Cationic Polyethylenimine Conjugates: A Preliminary Report

(188)Re(Rhenium) is easily obtained from an in-house (188)W/(188)Re generator that is similar to the current (99)Mo/(99m)Tc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of (188)Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of (188)Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, (188)Re perrhenate) were injected directly into the tumors. There were increases in the retention of (188)Re inside the tumor when PEI was incorporated with (188)Re compared to the use of free 188Re. The (188)Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that (188)Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support (188)Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection.

Development and Assessment Individual Maximum Permissible Dose Method of I-131 Therapy in High Risk Patients with Differentiated Papillary Thyroid Cancer / 대한핵의학회잡지

PURPOSE: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. MATERIALS AND METHODS: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age 50+/-11 years) of papillary thyroid cancer. Among them 43 patients were treated with or =9.25 GBq. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. RESULTS: MPD measured by CF method using tracer and therapeutic doses were 13.3+/-1.9 and 13.8+/-2.1 GBq, respectively (p=0.20). They showed a significant correlation (r=0.8, p< 0.0001). Exposed doses to blood measured by CF and biological methods were 1.54+/-0.03 and 1.78+/-0.03 Gy (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). CONCLUSION: Measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

Retention Characteristics of Tc-99m-Pullulan-Derivatives in CT26 Tumor of Mice / 대한핵의학회잡지

OBJECTIVE: Pullulan derivatives (PD) can be used to make self-assembled hydrogel nanoparticles which are responsive to ionic strength. The aim of this study is to evaluate the potential of PD as a retaining carrier of radioisotope inside tumors. MATERIALS AND METHODS: Four types of PD were evaluated which included pullulan acetate (PA), succinylated PA (SPA), PA-DTPA and SPA-DTPA conjugates. They were radiolabeled with Tc-99m. Labelling efficiencies were determined at 30 min, 1, 2, 4 and 12 hours after radiolabeling. CT-26 colon cancer cells were subcutaneously injected into Balb/c mice. After 2 weeks of subcutaneous injection, Tc-99m-labelled PD (Tc-99m-PD) were injected into the tumors. Whole body images of mice were obtained at 30 min, 1, 2, and 12 hr after intratumoral injection. All twenty mice were grouped into four groups by largest diameter; control A (largest diameter = 5 mm, n = 5), control B (largest diameter = 10 mm, n = 5), pullulan A (largest diameter = 5 mm, n = 5), pllulan B (largest diameter = 10 mm, n = 5). Dynamic images were obtained for 1 hour after intratumoral injection. Static images were obtained at 1 hr, 2 hr, 3 hr and 4 hr after intratumoral injection with Tc-99m pertechnetate and Tc-99m-PA. Target-to-background ratios and retention rates were calculated. RESULTS: Labeling efficiencies of PA, SPA, PA-DTPA and SPA-DTPA were 94.5 +/- 5.9%, 97.8 +/- 3.5% 94.2 +/- 3.8%, and 92.5 +/- 6.2%, respectively (p> 0.05). Percent retention rates (%RR) of PA and PA-DTPA were significantly higher than those of control, however, those of SP-DTPA and SPA became similar to control at 4 and 12 hr, respectively. %RR of pullulan A and pullulan B at 1, 4 and 8 hr is significantly higher than that of control (p < 0.05). However, %RR between pullulan A and pullulan B were similar. CONCLUSION: The ionic strength dependent PD-nanoparticles are retained in the tumor. No difference of %RR according to tumor size was noted. Therapeutic application of PD labelled with beta- or alpha- emitting radionuclides can be expected.