Tomohiko Yamane

Reduction of [(18)F]fluoromisonidazole uptake after neoadjuvant chemotherapy for head and neck squamous cell carcinoma.

PurposeThe purpose of this study was to investigate the changes of tumor hypoxia as a result of neoadjuvant chemotherapy (NAC) by measuring the changes of [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) uptake, as well as to look into the ability of [18F]FMISO PET to predict the NAC result.ProceduresA total of 13 patients with locally advanced head and neck squamous cell carcinoma underwent [18F]FMISO PET scans before and after NAC. For analysis of PET index, maximum standardized uptake value, tumor-to-muscle ratio, and hypoxic volume (HV) were measured.ResultsAll PET indexes of [18F]FMISO significantly decreased after NAC. Although HV in primary tumor and a few indexes before NAC in responder was lower than that in nonresponder, none of the indexes were statistically significant.ConclusionsPretreatment [18F]FMISO could not predict NAC outcome in this study. However, [18F]FMISO uptake significantly decreased after NAC, and [18F]FMISO PET seemed to be a useful noninvasive tool for detecting hypoxia reduction after NAC.

Human whole-body biodistribution and dosimetry of a new PET tracer, [11C]ketoprofen methyl ester, for imagings of neuroinflammation

INTRODUCTION Neuroinflammatory processes play an important role in the pathogenesis of Alzheimers disease and other brain disorders, and nonsteroidal anti-inflammatory drugs (NSAIDs) are considered therapeutic candidates. As a biomarker of neuroinflammatory processes, (11)C-labeled ketoprofen methyl ester ([(11)C]KTP-Me) was designed to allow cerebral penetration of ketoprofen (KTP), an active form of a selective cyclooxygenase-1 inhibitor that acts as an NSAID. Rat neuroinflammation models indicate that [(11)C]KTP-Me enters the brain and is retained in inflammatory lesions, accumulating in activated microglia. [(11)C]KTP-Me is washed out from normal tissues, leading to the present first-in-human exploratory study. METHODS [(11)C]KTP-Me was synthesized by rapid C-[(11)C]methylation of [(11)C]CH3I and the corresponding arylacetate precursor, purified with high-performance liquid chromatography, and prepared as an injectable solution including PEG400, providing radiochemical purity of >99% and specific activity of >25GBq/μmol at injection. Six young healthy male humans were injected with [(11)C]KTP-Me and scanned with PET camera to determine the early-phase brain time course followed by three whole-body scans starting 8, 20, and 40 min post-injection, together with sequential blood sampling and labeled metabolite analysis. RESULTS No adverse effects were observed during PET scanning after [(11)C]KTP-Me injection. [(11)C]KTP-Me was rapidly metabolized to (11)C-labeled ketoprofen ([(11)C]KTP) within 2-3 min and was gradually cleared from blood. The radioactivity entered the brain with an average peak cortical SUV of 1.5 at 2 min. The cortical activity was gradually washed out. Whole-body images indicated that the urinary bladder was the major excretory pathway. The organ with the highest radiation dose was the urinary bladder (average dose of 41μGy/MBq, respectively). The mean effective dose was 4.7μSv/MBq, which was comparable to other (11)C-labeled radiopharmaceuticals. CONCLUSION [(11)C]KTP-Me demonstrated a favorable dosimetry, biodistribution, and safety profile. [(11)C]KTP-Me entered the human brain, and the radioactivity was washed out from cerebral tissue. These data warrant further exploratory studies on patients with neuroinflammation.

Drug-induced pneumonitis detected earlier by 18F-FDG-PET than by high-resolution CT: a case report with non-Hodgkin’s lymphoma

Drug-induced pneumonitis is a serious and an unpredictable side effect of chemotherapy in patients with malignant lymphoma. We present the case of a 51-year-old man who developed drug-induced pneumonitis during chemotherapy for non-Hodgkin’s lymphoma in which pneumonitis was detected earlier by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) than by high-resolution computed tomography (HRCT). After five courses of chemotherapy, 18F-FDG-PET was performed for assessing residual lesions, and diffuse lung uptake was incidentally observed. No symptoms were present, and HRCT performed immediately following PET revealed no abnormalities. Mild dyspnea appeared 3 days after PET, and additional HRCT revealed patchy ground-glass opacities disseminated with the appearance of interlobular septum thickening. Drug-induced pneumonitis was finally diagnosed, and treatment was initiated. 18F-FDG-PET can be an imaging modality for detecting drug-induced pneumonitis at an extremely early stage in which HRCT is incapable of revealing any abnormal changes.

Impact of tissue photon attenuation in small animal cardiac PET imaging

OBJECTIVES Tissue photon attenuation is one of the essential artifacts requiring correction in clinical cardiac positron emission tomography (PET) imaging. However, due to small body size its impact on diagnostic accuracy in small rodents is considered to be limited or even ignorable. The present cardiac PET study compares lean and obese rats to determine the influence of tissue attenuation on quantitative assessment as well as regional tracer distribution. METHODS A dedicated small animal PET system equipped with a 57Co rotating source for transmission was used. To assess the impact of tissue attenuation in rats with different body sizes, cardiac 18F-FDG -PET studies for Zucker diabetic fatty rats (obese rats) and Zucker lean rats (lean rats) were performed. The radiotracer activity reduction by attenuation was compared between the two groups. Regional tracer distribution calculated with and without attenuation correction was also assessed. RESULTS The chest diameter was significantly longer in obese than in lean rats (5.6±0.3cm in obese and 4.5±0.2cm in lean rats, p<0.0001). Whereas the activity reduction by attenuation was significantly greater in obese than in lean rats (44.1±2.5% and 5.1±3.1%, p<0.0001), the regional variation of tissue attenuation among the ventricular walls was minimal in both lean (p=0.73) and obese rats (p=0.65). CONCLUSION Attenuation correction is indispensable for accurate comparison of cardiac tracer activity between animals with different body size, whereas it can be omitted for evaluation of regional tracer distribution.

Small-Animal PET Imaging of Isolated Perfused Rat Heart

The assessment of myocardial radiotracer kinetics, including cardiac extraction fraction and washout, requires the study of isolated perfused hearts to avoid analytic error due to tracer recirculation and systemic metabolites. Analysis of the isolated perfused rat heart by a high-resolution small-animal PET system may offer both reliable evaluation of cardiac tracer kinetics and tomographic images. Methods: An isolated perfused heart system was modified to accommodate the small PET gantry bore size. Isolated rat hearts were perfused via the Langendorff method under a constant flow of Krebs-Henseleit buffer containing 18F-FDG with a rate of 5 mL/min and placed in the field of view of the commercially available small-animal PET system. Dynamic PET imaging was then performed, with 18F-FDG uptake in the isolated perfused heart verified by γ counter measurements. Additionally, a rat heart of myocardial infarction was also studied in this system with static PET imaging. Results: Dynamic PET acquisition of the isolated heart under constant 18F-FDG infusion demonstrated continuous increase of activity in the heart. Correlation between cardiac activity (MBq) measured with the PET system and measurements made with the γ counter were excellent (R2 = 0.98, P < 0.001, n = 10). Tracer input rate (MBq/min) was also well correlated with cardiac tracer uptake rate (MBq/min) (R2 = 0.87, P < 0.001, n = 12). PET imaging of the heart with myocardial infarction showed a clear tracer uptake defect corresponding to the location of scar tissue identified by autoradiography and histology. Conclusion: Combining the Langendorff method of isolated rat heart perfusion with high-resolution small-animal PET allows for the reliable quantification of myocardial tracer kinetics. This novel assay is readily adapted to available small-animal PET systems and may be useful for understanding myocardial PET tracer kinetics.

Partial Volume Effect of thickness, inner diameter and positron range in small animal cardiac PET imaging

Partial Volume Effect (PVE), the image blurring caused by the finite spatial resolution of PET imaging system, can cause incorrect quantification of radioactivity especially for small objects. High-resolution small animal PET system has been developed for rodents, but sizes of rodent hearts are still close to the spatial resolution, that might cause significant PVE than human heart in clinic PET. The aim is to evaluate PVE of various heart-shaped phantoms in a small animal PET system utilizing Monte Carlo (MC) simulation. We built a simulation platform using a MC simulation (SimSET+GATE) and reconstruction software (STIR) based on the scanner configuration of a small animal PET system (Inveon). To confirm the spatial resolution, a line source in a water-filled cylinder was measured and simulated at the center of field of view. Simplified model of heart, combinations of thickness (0.5-18mm) and inner diameter (1-10mm) of hollow-cylindrical source, were simulated with F-18 and Ga-68. Sinograms of true events were rebinned by FORE and reconstructed by 2D OS-EM (32 updates) with attenuation correction and Gaussian post-filtering (1.4mm FWHM). Recovery coefficients (RCs) were estimated by average over 50% of maximum value using a big cylindrical source (40mm diameter) as the reference. RC at the specific size was estimated by bilinear interpolation. Averaged FWHMs on the sinogram for F-18 and Ga-68 were about 1.7 and 3.9mm in MC simulation and 1.8 and 3.7mm in real measurement, respectively. RCs were 30.4% and 21.2% for F-18 and 20.5% and 14.5% for Ga-68 at the end of diastolic phase (ED) of the left ventricle (LV) of a rat and a mouse heart size (measured on MRI; 8 and 1 mm, 4 and 0.65mm for inner diameter and wall thickness, respectively). We developed a MC simulation platform and observed considerable count reductions (70-85%) by PVE in rodent heart size with small animal PET. This platform has the further potential use for developing new PVE compensation algorithms.

FMISO-PET Is a Predictor of Survival Prognosis in Head and Neck Squamous Cell Carcinoma

Objective: Evaluate the usefulness of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) prior to treatment of head and neck squamous cell carcinoma. Method: We evaluated 30 lesions from 17 patients with HNSCC underwent pretreatment FMISO-PET. SUVmax and tumor-to-muscle ratios (TMR) were measured as hypoxia indicators and tumors were defined as hypoxic or normoxic. Between the hypoxic tumor group and the normoxic tumor group, local control rates with radiotherapy and survival prognosis were compared. Results: Radiotherapy outcome: Local control rates with radiotherapy (20-month median follow-up duration) were significantly lower for the hypoxic tumor group using either SUVmax or TMR as the hypoxic indicator (P = .02 and .04-respectively). Patient Prognosis (operation or radiotherapy): No significant difference was found between the hypoxic and the normoxic patient groups for event-free survival rate (12-month median follow-up duration) using either SUVmax or TMR as the hypoxic indicator (P = .07 and .13, respectively). On the other hand, disease specific survival rate (21-month median follow-up duration) was significantly lower in the hypoxic group defined by SUVmax (P = .04), but was not by TMR (P = .57). Conclusion: The current results suggest that the radiotherapy outcome and survival prognosis (operation or radiotherapy) in HNSCC may be predicted by carrying out [18F]FMISO -PET/CT before treatment.

Interrater variability of image interpretation for PIB-PET in the diagnosis of Alzheimer's disease

INTERPRETATION FOR PIB-PET IN THE DIAGNOSIS OFALZHEIMER’S DISEASE Tomohiko Yamane, Hidehito Nagai, Tomoyuki Nishio, Yasuhiko Ikari, Yoko Makishi, Kazunari Ishii, Kenji Ishii, Takashi Kato, Kengo Ito, Michio Senda, Institute of Biomedical Research and Innovation, Kobe, Japan; 2 Kinki University, Osaka-Sayama, Japan; 3 Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; 4 National Center for Geriatrics and Gerontology, Obu, Japan.

Erratum to: Clinical impact of 11C-methionine PET on expected management of patients with brain neoplasm

Fig. 2 MRI T1-weighted image with contrast media (a) and fluid attenuated inversion recovery (b), and C-MET PET (c) images of cerebellar tumor (arrows). The Chief complaint was weak abnormal feeling in the legs for several months. This lesion was found as high intensity area in images of fluid attenuated inversion recovery. However, as this lesion did not enhance and symptom was not progressive, the physician decided to watch the patient for several months without any treatment. However, increased uptake in C-MET PET led this patient to biopsy and operation that followed. Finally, this case was diagnosed as diffuse astrocytoma (grade II)