An one-pot two-step automated synthesis of [18F]T807 injection, its biodistribution in mice and monkeys, and a preliminary study in humans.

[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/µmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 µSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) µSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons.

Neuroimaging findings in a brain with Niemann-Pick type C disease.

Niemann-Pick type C disease (NPC) is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI), magnetic resonance spectrography (MRS) and 18-fluoro-2-deoxyglucose positron emission tomography (PET) imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years) demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years) revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years) showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

Predicting chemotherapy response to paclitaxel-based therapy in advanced non-small-cell lung cancer (stage IIIb or IV) with a higher T stage (> T2). Technetium-99m methoxyisobutylisonitrile chest single photon emission computed tomography and P-glycoprotein express ion.

OBJECTIVE: The aim of this study was to compare technetium-99m methoxyisobutylisonitrile (Tc-MIBI) chest single photon emission computed tomography (SPECT) results, immunohistochemical analyses of P-glycoprotein (Pgp) expression and response to paclitaxel in non-small-cell lung cancer (NSCLC). METHODS: Before chemotherapy with paclitaxel, 30 patients with stage IIIb or IV NSCLC were enrolled in this study. Early chest SPECT was performed 10 min after intravenous injection of Tc-MIBI. Tc-MIBI chest SPECT images were qualitatively interpreted. Early tumor-to-normal lung ratios (T/NL) were calculated quantitatively. Immunohistochemical analyses were performed on multiple nonconsecutive sections of the biopsy specimens to determine Pgp expression. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. RESULTS: All 15 (100%) cases with good response and negative Pgp expression had positive results of early Tc-MIBI chest SPECT. Ten of 15 (67%) cases with poor response and positive Pgp expression had negative results of early Tc-MIBI chest SPECT. These early T/NL ratios (3.3 +/- 0.8 for the 15 patients with good response and 2.0 +/- 0.2 for the 5 patients with poor response) in lung cancer could be detected on early Tc-MIBI chest SPECT. The difference was significant (p < 0.05) by an independent Student t test. However, no significant differences were found for other prognostic factors (age, sex, body weight loss, performance status, tumor cell type, and tumor stage) between the good and poor response groups. CONCLUSION: Early Tc-MIBI chest SPECT can be used to understand the Pgp expression in NSCLC and to quickly predict chemotherapy response to paclitaxel.