Dae Hyuk Moon

Performance Measurement of the microPET Focus 120 Scanner

The microPET Focus 120 scanner is a third-generation animal PET scanner dedicated to rodent imaging. Here, we report the results of scanner performance testing. Methods: A 68Ge point source was used to measure energy resolution, which was determined for each crystal and averaged. Spatial resolution was measured using a 22Na point source with a nominal size of 0.25 mm at the system center and various off-center positions. Absolute sensitivity without attenuation was determined by extrapolating the data measured using an 18F line source and multiple layers of absorbers. Scatter fraction and counting rate performance were measured using 2 different cylindric phantoms simulating rat and mouse bodies. Sensitivity, scatter fraction, and noise equivalent counting rate (NECR) experiments were repeated under 4 different conditions (energy window, 250∼750 keV or 350∼650 keV; coincidence window, 6 or 10 ns). A performance phantom with hot-rod inserts of various sizes was scanned, and several animal studies were also performed. Results: Energy resolution at a 511-keV photopeak was 18.3% on average. Radial, tangential, and axial resolution of images reconstructed with the Fourier rebinning (FORE) and filtered backprojection (FBP) algorithms were 1.18 (radial), 1.13 (tangential), and 1.45 mm full width at half maximum (FWHM) (axial) at center and 2.35 (radial), 1.66 (tangential), and 2.00 mm FWHM (axial) at a radial offset of 2 cm. Absolute sensitivities at transaxial and axial centers were 7.0% (250∼750 keV, 10 ns), 6.7% (250∼750 keV, 6 ns), 4.0% (350∼650 keV, 10 ns), and 3.8% (350∼650 keV, 6 ns). Scatter fractions were 15.9% (mouse phantom) and 35.0% (rat phantom) for 250∼750 keV and 6 ns. Peak NECR was 869 kcps at 3,242 kBq/mL (mouse phantom) and 228 kcps at 290 kBq/mL (rat phantom) at 250∼750 keV and 6 ns. Hot-rod inserts of 1.6-mm diameter were clearly identified, and animal studies illustrated the feasibility of this system for studies of whole rodents and mid-sized animal brains. Conclusion: The results of this independent field test showed the improved physical characteristics of the F120 scanner over the previous microPET series systems. This system will be useful for imaging studies on small rodents and brains of larger animals.

[18F]Fluorothymidine Positron Emission Tomography before and 7 Days after Gefitinib Treatment Predicts Response in Patients with Advanced Adenocarcinoma of the Lung

Purpose: To evaluate the usefulness of 3′-deoxy-3′-[18F]fluorothymidine (FLT)-positron emission tomography (PET) for predicting response and patient outcome of gefitinib therapy in patients with adenocarcinoma of the lung. Experimental Design: Nonsmokers with advanced or recurrent adenocarcinoma of the lung were eligible. FLT-PET images of the thorax were obtained before and 7 days after the start of gefitinib (250 mg/d) therapy, the maximum standardized uptake values (SUVmax) of primary tumors were measured, and the percent changes in SUVmax were calculated. After 6 weeks of therapy, the responses were assessed by computed tomography of the chest. Results: Among 31 patients who were enrolled, we analyzed 28 patients for whom we had complete data. Chest computed tomography revealed partial response in 14 (50%), stable disease in 4 (14%), and progressive disease in 10 (36%) after 6 weeks of treatment. Pretreatment SUVmax of the tumors did not differ between responders and nonresponders. At 7 days after the initiation of therapy, the percent changes in SUVmax were significantly different (−36.0 ± 15.4% versus 10.1 ± 19.5%; P < 0.001). Decrease of >10.9% in SUVmax was used as the criterion for predicting response. The positive and negative predictive values were both 92.9%. The time to progression was significantly longer in FLT-PET responders than nonresponders (median, 7.9 versus 1.2 months; P = 0.0041). Conclusion: FLT-PET can predict response to gefitinib 7 days after treatment in nonsmokers with advanced adenocarcinoma of the lung. The change in tumor SUVmax obtained by FLT-PET seems to be a promising predictive variable.

Subregional Patterns of Preferential Striatal Dopamine Transporter Loss Differ in Parkinson Disease, Progressive Supranuclear Palsy, and Multiple-System Atrophy

Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of 18F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane (18F-FP-CIT) PET in differentiating PSP and MSA from PD. Methods: Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with 18F-FP-CIT PET. The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum [VS], anterior caudate [AC], posterior caudate, anterior putamen, posterior putamen [PP], and ventral putamen [VP]) and 1 occipital VOI template. The nondisplaceable binding potential (BPND) and intersubregional ratio (ISR; defined as the ratio of the BPND of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated. Results: The BPND of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P < 0.05). The BPND of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BPND of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (<0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (>0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively. The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD. Conclusion: Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features.

Induction of thymidine kinase 1 after 5-fluorouracil as a mechanism for 3'-deoxy-3'-[18F]fluorothymidine flare

Imaging the pharmacodynamics of anti-cancer drugs may allow early assessment of anti-cancer effects. Increases in 3-deoxy-3-[(18)F]fluorothymidine ([(18)F]FLT) uptake early after thymidylate synthase inhibition (TS) inhibition, the so-called flare response, is considered to be largely due to an increase in binding sites for type-1 equilibrative nucleoside transporter. We investigated the induction of thymidine kinase 1 (TK1) after 5-fluorouracil (5-FU) treatment as one of mechanisms for [(18)F]FLT flare. Exposure of nine cancer cell lines to 5-FU for 24h induced a 2.5- to 3.5-fold increase in [(18)F]FLT uptake, significantly higher than the 1.5-fold increase observed 2h after treatment. The increase of [(18)F]FLT uptake 24h after 5-FU exposure accompanied TK1 induction in most cell lines. In representative cell lines (A431 and HT29), 5-FU time-dependently increased [(18)F]FLT uptake, kinase activity and the levels of protein and mRNA for TK1, sequential cyclin E and A induction, and G(1)-S phase transition. Cycloheximide treatment and knockdown of TK1 completely inhibited 5-FU-induced [(18)F]FLT flare. On the other hand, HCT8 cells showed a biphasic [(18)F]FLT flare with lacked TK1 induction in response to the dosage of 5-FU. Cycloheximide did not inhibit 5-FU-induced [(18)F]FLT flare in this cells. In vivo dynamic [(18)F]FLT-PET and ex vivo analysis in HT29 tumor-bearing mice showed significantly increased [(18)F]FLT flux and TK1 activity of tumor tissue 24h after 5-FU administration (P<0.05). Conclusively, 5-FU induced TK1 and TK1-mediated high [(18)F]FLT flare in most of cell lines. [(18)F]FLT-PET may be used to assess pharmacodynamics of TS inhibitor by a mechanism involving TK1 induction.

Kinetic Modeling of 3′-Deoxy-3′-18F-Fluorothymidine for Quantitative Cell Proliferation Imaging in Subcutaneous Tumor Models in Mice

3′-Deoxy-3′-18F-fluorothymidine (18F-FLT) is a thymidine analog that was developed for measuring tumor proliferation with PET. The aim of this study was to establish a kinetic modeling analysis method for quantitative 18F-FLT PET studies in subcutaneous tumor models in mice. Methods: To explore the validity of an image-derived left ventricular input function, we measured equilibrium constants for plasma and whole blood and metabolite fractions in blood after 18F-FLT injection. In parallel, dynamic 18F-FLT PET scans were acquired in 24 mice with a small-animal dedicated PET scanner to compare arterial blood activities obtained by PET and blood sampling. We then investigated kinetic models for 18F-FLT in human epithelial carcinoma (A431) and Lewis lung carcinoma tumor models in mice. Three-compartment models with reversible phosphorylation (k4 ≠ 0, 3C5P) and irreversible phosphorylation (k4 = 0, 3C4P) and a 2-compartment model (2C3P) were examined. The Akaike information criterion and F statistics were used to select the best model for the dataset. Gjedde–Patlak graphic analysis was performed, and standardized uptake values in the last frame were calculated for comparison purposes. In addition, quantitative PET parameters were compared with Ki-67 immunostaining results. Results: 18F-FLT equilibrated rapidly (within 30 s) between plasma and whole blood, and metabolite fractions were negligible during PET scans. A high correlation between arterial blood sampling and PET data was observed. For 120-min dynamic PET data, the 3C5P model best described tissue time–activity curves for tumor regions. The net influx of 18F-FLT (KFLT) and k3 obtained with this model showed reasonable intersubject variability and discrimination ability for tumor models with different proliferation properties. The KFLT obtained from the 60- or 90-min data correlated well with that obtained from the 120-min data as well as with the Ki-67 results. Conclusion: The image-derived arterial input function was found to be feasible for kinetic modeling studies of 18F-FLT PET in mice, and kinetic modeling analysis with an adequate compartment model provided reliable kinetic parameters for measuring tumor proliferation.

Bone SPECT imaging of vertebral hemangioma : correlation with MR imaging and symptoms

To evaluate the bone SPECT findings of vertebral hemangioma and their relationship to symptoms and MRI findings, the authors reviewed planar and SPECT bone scans and MR images of 15 vertebral hemangioma in 10 patients. All planar bone scan images demonstrated normal findings, except one. SPECT images demonstrated normal findings in 11 vertebral hemangioma less than 3 cm in diameter. Three of four vertebral hemangioma that were 3 cm or larger showed abnormally increased or decreased uptake on SPECT images. There was a disparity between SPECT imaging and MRI.

Dipyridamole Tl-201 SPECT imaging in patients with myocardial bridging

PURPOSE: Exercise-induced myocardial perfusion abnormalities have been reported in patients with myocardial bridging, possibly by tachycardia-induced shortening of diastole. Dipyridamole TI-201 SPECT findings were evaluated in patients with myocardial bridging to assess perfusion abnormalities during dipyridamole stress. MATERIALS AND METHODS: Dipyridamole TI-201 SPECT images of 12 patients with myocardial bridging (> or = 50% systolic narrowing) were evaluated. The peak heart rate during dipyridamole stress was less than 110 beats/min in all patients. The control group was 118 patients with fixed left anterior descending artery (LAD) disease. RESULTS: Fourteen sites of systolic arterial narrowing were present in LAD: two in mid-LAD, seven in distal LAD, and five in septal branches. Dipyridamole TI-201 SPECT showed reversible perfusion defects in three of six sites with 50% to 70% systolic narrowing and seven of eight sites with more than 80% systolic narrowing. Overall, 71% (10 of 14) had a reversible perfusion defect. Five patients with septal branch compression had a perfusion defect in the midanteroseptal wall without an apical abnormality. In the control group, no patient had an isolated perfusion defect in the midanteroseptal wall or septal branch disease (5 of 12 compared with 0 of 118; P < 0.001). CONCLUSIONS: Perfusion abnormalities on dipyridamole TI-201 SPECT are observed in LAD or its branches in patients with high-grade myocardial bridging. Myocardial bridging may decrease coronary flow reserve but not necessarily via tachycardia. Isolated perfusion defects in the midanteroseptal wall may be a characteristic finding of septal branch compression, because a fixed lesion involving a septal branch only is rare.

Pelioid-type hepatocellular carcinoma masquerading as a hepatic hemangioma on technetium-99m red blood cell scintigraphy.

Technetium-99m red blood cell (RBC) scintigraphy is a very specific method to differentiate a hemangioma from other hepatic masses. The authors report a case of hepatocellular carcinoma that showed a focal area of increased uptake on Tc-99m RBC SPECT in a 60-year-old man. Dynamic computed tomography and angiography revealed features of both hemangioma and hepatocellular carcinoma. Pathologic examination showed that the portion of the hepatocellular carcinoma that showed increased uptake on Tc-99m RBC scintigraphy had peliosis, which is the likely cause of the radiotracer avidity.

Assessment of Cerebral Glucose Metabolism in Cat Deafness Model: Strategies for Improving the Voxel-Based Statistical Analysis for Animal PET Studies

PurposeThe aim of this study was to establish the procedures for 3D voxel-based statistical analysis of 2-deoxy-2-[18F]fluro-d-glucose-positron emission tomography (FDG-PET) images of a cat’s brain obtained using a small animal-dedicated PET system and to assess the utility of this approach in investigating the cerebral glucose metabolism in an animal model of cortical deafness.ProceduresThis study compared several different strategies for the spatial processing of PET data acquired twice from eight cats before and after inducing deafness in terms of the comparability of the statistical analysis results to the established pattern of the cerebral glucose metabolic changes in the deaf animals.ResultsThe accuracy of the spatial preprocessing procedures and the statistical significance of the comparison were improved by removing the background activities outside the brain regions. The use of the spatial normalization parameters obtained from the mean image of the realigned data set for individual data also helped improve the statistical significance of the paired t testing. It was also found that an adjustment of the registration options was also important for increasing the precision of the realignment.ConclusionsA method for voxel-based analysis of the PET data of a cat’s brain was optimized. The results demonstrated the high localization accuracy and specificity of this method, which is expected to be useful for examining the brain PET data of medium-sized animals such as cats.

FDG-PET as a Potential Tool for Selecting Patients with Advanced Non–Small Cell Lung Cancer Who May Be Spared Maintenance Therapy after First-Line Chemotherapy

Purpose: To investigate whether 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) may be a potential tool to select a subgroup of patients who might be spared maintenance treatment, if the metabolic response after first-line chemotherapy could predict time-to-progression (TTP). Experimental Design: A total of 43 patients who underwent baseline FDG-PET scan and did not show disease progression (DP) after 4 cycles of first-line chemotherapy were enrolled and underwent second FDG-PET 3 weeks after completion of the first-line chemotherapy. The primary endpoint was to compare percent decrease in maximum standard uptake value (SUVmax) between early (TTP after second PET examination <8 weeks) and late (TTP ≥8 weeks) DP subgroups. Secondary endpoints were to determine whether fractional decrease in SUVmax could predict TTP and overall survival (OS), both calculated from the date of the second FDG-PET. Results: Percent decreases in SUVmax in late DP subgroup were greater than those in early DP subgroup (mean reduction, 54.7% ± 27.2% vs. 27.8% ± 46.8%, P = 0.021). Receiver operating characteristic curves identified a 50.0% decrease in SUVmax as the optimal threshold to distinguish these subgroups. Using this value as the cutoff resulted in a positive predictive value of 82.6% and negative predictive value of 60.0% in predicting TTP ≥8 weeks. Patients with SUVmax decrease <50% had significantly longer median TTP (3.0 vs. 1.5 months, P = 0.001) and OS (not reached vs. 14.2 months, P = 0.003). Conclusions: Fractional decrease in SUVmax of the main lesion after completion of 4 cycles of chemotherapy may discriminate patients with TTP ≥8 weeks and predict TTP and OS in patients with advanced NSCLC. Clin Cancer Res; 17(15); 5093–100. ©2011 AACR.