Dedicated phantom tools using traceable 68Ge/68Ga point-like sources for dedicated-breast PET and positron emission mammography scanners.

Since the early 2000s, many types of positron emission tomography (PET) scanners dedicated to breast imaging for the diagnosis of breast cancer have been introduced. However, conventional performance evaluation methods developed for whole-body PET scanners cannot be used for such devices. In this study, we developed phantom tools for evaluating the quantitative accuracy of positron emission mammography (PEM) and dedicated-breast PET (dbPET) scanners using novel traceable point-like 68Ge/68 Ga sources. The PEM phantom consisted of an acrylic cube (100 × 100 × 40 mm) and three point-like sources. The dbPET phantom comprised an acrylic cylinder (ø100 × 100 mm) and five point-like sources. These phantoms were used for evaluating the fundamental responses of clinical PEM and dbPET scanners to point-like inputs in a medium. The results showed that reasonable recovery values were obtained based on region-of-interest analyses of the reconstructed images. The developed phantoms using traceable 68Ge/68 Ga point-like sources were useful for evaluating the physical characteristics of PEM and dbPET scanners. Thus, they offer a practical, reliable, and universal measurement scheme for evaluating various types of PET scanners using common sets of sealed sources.

New standards for phantom image quality and SUV harmonization range for multicenter oncology PET studies.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards.

Clinical practice guidelines for high-resolution breast PET, 2019 edition.

Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name "dedicated breast PET" from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, "breast PET" has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging.

Validation of scatter limitation correction to eliminate scatter correction error in oxygen-15 gas-inhalation positron emission tomography images.

OBJECTIVE: High levels of radioactivity inside a facemask cause scatter correction (SC) errors that appear as photopenic artifacts on quantitative oxygen-15 (O) gas-inhalation positron emission tomography (PET) images. The present study aimed to validate the ability of scatter limitation correction (SLC) to eliminate SC errors in O gas-inhalation PET images acquired from patients and a phantom. MATERIALS AND METHODS: We analyzed the SC errors in phantom images and calculated parametric images of the cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2). Phantoms comprised a cylinder and paper with radioactivity to simulate a facemask during (O)O2 gas inhalation. Parametric images were calculated from O gas-inhalation PET images of ten participants. All PET data were reconstructed using conventional SC as model-based SC and SLC. Images acquired from the phantoms and parametric images were assessed visually and quantitatively in the presence and absence of SC error. RESULTS: SC error was evident in images derived from the paper phantom and at the slice level of the cerebellum in CBF, OEF, and CMRO2 images. The radioactivity concentration in the cylindrical phantom with the paper phantom significantly improved with SLC. The SLC also increased the quantitative indices of CBF, OEF, and CMRO2 by 23.8, 42.2, and 44.4%, respectively. CONCLUSION: SLC visually eliminated the SC error and increased the quantitative parameters on O gas-inhalation images derived from a phantom and from patients.

Increased Binding Potential of Brain Adenosine A1 Receptor in Chronic Stages of Patients with Diffuse Axonal Injury Measured with [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine Positron Emission Tomography Imaging.

The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. Three PET examinations were sequentially performed to measure A1R binding with 11C-MPDX, glucose metabolism with 18F-fluorodeoxyglucose (FDG), and central benzodiazepine receptor binding with 11C-flumazenil (FMZ), and decreases of 11C-FMZ uptake indicate neuronal loss. 11C- MPDX did not depict any lesion with significantly decreased nondisplaceable binding potential (BPND) in comparison to healthy controls (14 men) in region of interest (ROI) analysis. Instead, it showed a significant increase of BPND in the lower frontal and posterior cingulate cortexes and rolandic area (p < 0.05) in ROI analysis. In 18F-FDG PET, the standardized uptake values (SUVs) ratio to the whole brain were decreased in anterior and posterior cingulate gyrus compared to controls (14 men and 9 women; p < 0.01). In 11C-FMZ PET, the SUV ratio to the cerebellum was decreased in anterior cingulate gyrus in ROI analysis (controls, 9 men and 6 women; p < 0.01). The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.

Effects of a novel tungsten-impregnated rubber neck shield on the quality of cerebral images acquired using 15O-labeled gas.

The present study aimed to validate the effects of a novel tungsten-impregnated rubber neck shield on the quality of phantom and clinical 15O-labeled gas positron emission tomography (PET) images. Images were acquired in the presence or absence of a neck shield from a cylindrical phantom containing [15O]H2O (phantom study) and from three individuals using [15O]CO2, [15O]O2 and [15O]CO gas (clinical study). Data were acquired in three-dimensional (3D) mode using a Discovery PET/CT 710. Values for cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and cerebral metabolic rate of oxygen with and without the neck shield were calculated from 15O-labeled gas images. Arterial radioactivity and count characteristics were evaluated in the phantom and clinical studies. The coefficient of variance (CV) for the phantom study and the standard deviation (SD) for functional images were also analyzed. The neck shield decreased the random count rates by 25-59% in the phantom and clinical studies. The noise equivalent count rate (NECR) increased by 44-66% in the phantom and clinical studies. Random count rates and NECR in [15O]CO2 images significantly differed with and without the neck shield. The improvement in visual and physical image quality with the neck shield was not observed in the phantom and clinical studies. The novel neck shield reduced random count rate and improved NECR in a 3D PET study using 15O-labeled gas. The image quality with the neck shield was similar to that without the neck shield.

Adenosine A1 receptors measured with 11 C-MPDX PET in early Parkinson's disease.

Adenosine A1 receptors (A1 Rs) interact negatively with dopamine D1 receptors (D1 Rs) in neurons of the basal ganglia's direct pathway, while adenosine A2A receptors (A2A Rs) negatively interact with dopamine D2 receptors (D2 Rs) in indirect-pathway neurons. The aim of this study was to investigate the cerebral density of A1 Rs in Parkinson's disease (PD) in its early stages, using PET scans with the radioligand 8-dicyclopropylmethyl-1-11 C-methyl-3-propylxanthine (11 C-MPDX). We studied 10 drug-naïve patients with early PD. Each patient was also examined for dopamine transporters (DATs) and D2 Rs by PET using 11 C-2-ß-carbomethoxy-3-ß-(4-fluorophenyl)-tropane (11 C-CFT) and 11 C-raclopride (11 C-RAC), respectively. Ten elderly, healthy volunteers were recruited as controls for 11 C-MPDX PET scanning and eight elderly volunteers were recruited as controls for 11 C-CFT and 11 C-RAC PET scanning. The PET scans revealed a decrease in the uptake ratio index (URI) of 11 C-CFT and an increase in the URI of 11 C-RAC in patients. In the temporal lobe, the binding potential for 11 C-MPDX was higher in the patient group than in healthy subjects, but not in the other regions examined, including the striatum. In patients, we observed motor-symptom asymmetry and a relationship between parkinsonism and the striatal density of DATs, but not A1 R density. In the putamen of early PD, asymmetrical down-regulation of A2A Rs is likely a compensatory mechanism in response to a decrease in dopamine. However, our study suggests that A1 Rs are unaltered in the putamen of early PD.

Age-Related Decrease in Male Extra-Striatal Adenosine A1 Receptors Measured Using11C-MPDX PET.

Adenosine A1 receptors (A1Rs) are widely distributed throughout the entire human brain, while adenosine A2A receptors (A2ARs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of A1R in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the A1Rs using 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine (11C-MPDX). We previously reported that the density of A1Rs decreased with age in the human striatum, although we could not observe an age-related change in A2ARs. The aim of this study was to investigate the age-related change of the density of A1Rs in the thalamus and cerebral cortices of healthy participants using 11C-MPDX PET. We recruited eight young (22.0 ± 1.7 years) and nine elderly healthy male volunteers (65.7 ± 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting with the injection of 11C-MPDX. We placed the circular regions of interest of 10 mm in diameter in 11C-MPDX PET images. The values for the binding potential (BPND) of 11C-MPDX in the thalamus, and frontal, temporal, occipital, and parietal cortices were calculated using a graphical analysis, wherein the reference region was the cerebellum. BPND of 11C-MPDX was significantly lower in elderly participants than young participants in the thalamus, and frontal, temporal, occipital, and parietal cortices. In the human brain, we could observe the age-related decrease in the distribution of A1Rs.

Evaluation of a New Motion-correction Algorithm Using On-rigid Registration in Respiratory-gated PET/CT Images of Liver Tumors.

OBJECTIVE: The present study aimed to determine the qualitative and quantitative accuracy of the Q.Freeze algorithm in PET/CT images of liver tumors. METHODS: A body phantom and hot spheres representing liver tumors contained 5.3 and 21.2 kBq/mL of a solution containing 18F radioactivity, respectively. The phantoms were moved in the superior-inferior direction at a motion displacement of 20 mm. Conventional respiratory-gated (RG) and Q.Freeze images were sorted into 6, 10, and 13 phase-groups. The SUVave was calculated from the background of the body phantom, and the SUVmax was determined from the hot spheres of the liver tumors. Three patients with four liver tumors were also clinically assessed by whole-body and RG PET. The RG and Q.Freeze images derived from the clinical study were also sorted into 6, 10 and 13 phase-groups. Liver signal-to-noise ratio (SNR) and SUVmax were determined from the RG and Q.Freeze clinical images. RESULTS: The SUVave of Q.Freeze images was the same as those derived from the body phantom using RG. The liver SNR improved with Q.Freeze, and the SUVsmax was not overestimated when Q.Freeze was applied in both the phantom and clinical studies. Q.Freeze did not degrade the liver SNR and SUVmax even though the phase number was larger. CONCLUSIONS: Q.Freeze delivered qualitative and quantitative motion correction than conventional RG imaging even in 10-phase groups.

Clinical benefit of 11C methionine PET imaging as a planning modality for radiosurgery of previously irradiated recurrent brain metastases.

OBJECT: Stereotactic radiosurgery with gamma knife (GK-SRS) generally improves the focal control of brain metastases. Yet in cases of focal recurrence at a previous radiation site, MRI is often imperfect in differentiating between active tumor and radiation injury. We have examined whether the use of C methionine (MET) with PET will facilitate this differentiation and improve the outcome of GK-SRS for focally recurrent brain metastases after prior treatment. METHODS: Eighty-eight patients underwent GK-SRS for postirradiation recurrent brain metastases. Thirty-four patients received radiation in areas manifesting high MET uptake (PET group) in a dose-planning procedure using MET-PET/MRI fusion images. Fifty-four patients referred from other institutes received radiation based on dose planning information obtained from MRI (MRI group). RESULTS: Sex, age, and the ratio of breast cancer differed significantly between the MRI and PET groups. The total irradiation volume was significantly smaller in the PET group, and the minimal irradiation dose was significantly higher. In a multivariable statistical analysis, the use of MET-PET (P = 0.02) was independently associated with prolonged overall survival after treatment, Karnofsky performance status (P = 0.002), the number of lesions (P = 0.03), and patient's sex (P = 0.02). The median survival time was significantly longer in the PET group (18.1 months) than in the MRI group (8.6 months) (P = 0.01). CONCLUSION: 11C methionine-PET/MRI fusion images for dose planning lengthened survival in patients undergoing GK-SRS for focally recurrent brain metastases.

Test-retest variability of adenosine A2A binding in the human brain with (11)C-TMSX and PET.

BACKGROUND: The goal of the present study was to evaluate the reproducibility of cerebral adenosine A2A receptor (A2AR) quantification using (11)C-TMSX and PET in a test-retest study. METHODS: Five healthy volunteers were studied twice. The test-retest variability was assessed for distribution volume (V T) and binding potential relative to non-displaceable uptake (BPND) based on either metabolite-corrected arterial blood sampling or a reference region. The cerebral cortex and centrum semiovale were used as candidate reference regions. RESULTS: Test-retest variability of V T was good in all regions (6% to 13%). In the putamen, BPND using the centrum semiovale displayed a lower test-retest variability (3%) than that of BPND using the cerebral cortex as a reference region (5%). The noninvasive method showed a higher or similar level of test-retest reproducibility compared to the invasive method. CONCLUSIONS: Binding reproducibility is sufficient to use (11)C-TMSX as a tool to measure the change in A2AR in the human brain.

Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies.

OBJECTIVE: We investigated the whole-body biodistributions and radiation dosimetry of five (11)C-labeled and one (18)F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. METHODS: The radiotracers investigated were (11)C-SA4503, (11)C-MPDX, (11)C-TMSX, (11)C-CHIBA-1001, (11)C-4DST, and (18)F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. RESULTS: The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. CONCLUSIONS: Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.

Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory tissue.

INTRODUCTION: Longitudinal changes of 4'-[methyl-(11)C]thiothymidine ([(11)C]4DST) uptake were evaluated in turpentine-induced inflammation. METHODS: Turpentine (0.1 ml) was injected intramuscularly into the right hind leg of male Wistar rats. Longitudinal [(11)C]4DST uptake was evaluated by the tissue dissection method at 1, 2, 4, 7, and 14 days after turpentine injection (n=5). The tumor selectivity index was calculated using the previously published biodistribution data in C6 glioma-bearing rats. Dynamic PET scan was performed on day 4 when maximum [(11)C]4DST uptake was observed during the longitudinal study. Histopathological analysis and Ki-67 immunostaining were also performed. RESULTS: The uptake of [(11)C]4DST in inflammatory tissue was significantly increased on days 2-4 after turpentine injection, and then decreased. On day 14, tracer uptake returned to the day 1 level. The maximum SUV of inflamed muscle was 0.6 and was 3 times higher than that of the contralateral healthy muscle on days 2-4 after turpentine injection. However, tumor selectivity index remains very high (>10) because of the low inflammation uptake. A dynamic PET scan showed that the radioactivity in inflammatory tissues peaked at 5 min after [(11)C]4DST injection, and then washed out until 20 min. At intervals >20 min, radioactivity levels were constant and double that of healthy muscle. The changes in Ki-67 index were paralleled with those of [(11)C]4DST uptake, indicating cell proliferation-dependent uptake of [(11)C]4DST in inflammatory tissues. CONCLUSION: In our animal model, low but significant levels of [(11)C]4DST uptake were observed in subacute inflammation.

Increased adenosine A1 receptor levels in hemianopia patients after cerebral injury: an application of PET using 11C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine.

PURPOSE: The aim of this study was to apply positron emission tomography (PET) with C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for adenosine A1 receptor (A1R), to patients with hemianopia caused by brain injury to study neurorepair mechanisms in the brain. PATIENTS AND METHODS: Four patients with homonymous hemianopia and 15 healthy subjects were examined using PET to measure cerebral glucose metabolism, C-flumazenil (FMZ) binding to the central benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET examinations were obtained. The ROIs were referenced using the data for homologous regions in the contralateral hemisphere [ipsilateral/contralateral (I/C) ratio]. RESULTS: The I/C ratios for cerebral glucose metabolism and FMZ binding were low in the primary visual cortex (PVC) and visual association cortex in all the patients, whereas MPDX binding increased in the PVC in patients 1 and 2. Patients 1 and 2 experienced improvement in their visual field after 1 year. However, the other 2 patients showed no changes. We observed an increase in MPDX binding to A1R in the injured portion of the PVC in the patients who recovered. CONCLUSIONS: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis and understanding the compensatory and reorganization processes in hemianopia caused by organic brain damage.

Differential effects of age on human striatal adenosine A1 and A(2A) receptors.

The aim of this study was to investigate the effect of age on the distribution of adenosine A1 receptors (A1Rs) and adenosine A(2A) receptors (A(2A)Rs) in the striatum of healthy subjects using PET imaging with 8-dicyclopropylmethyl-1-[¹¹C]methyl-3-propylxanthine ([¹¹C]MPDX) and [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX), respectively. We recruited 8 young (22.0 ± 1.7 years) and 10 elderly (65.4 ± 7.6 years) volunteers to undergo [¹¹C]MPDX PET scanning, and 11 young (22.7 ± 2.7 years) and six elderly (60.7 ± 8.5 years) volunteers to undergo [¹¹C]TMSX PET scanning. A dynamic series of decay-corrected PET scans was performed for 60 min following injection of [¹¹C]MPDX or [¹¹C]TMSX. We calculated the binding potential (BP(ND) ) of [¹¹C]MPDX and distribution volume ratio (DVR) of [¹¹C]TMSX in the striatum. The BP(ND) of [¹¹C]MPDX was significantly lower in elderly than in young subjects, both in the putamen and head of the caudate nucleus. The BP(ND) was negatively correlated with age in both the putamen and the head of the caudate nucleus. However, no difference was found between the DVR of [¹¹C]TMSX in the striata of young and elderly subjects, nor was there a correlation between age and the DVR of [¹¹C]TMSX. The effect of age on the distribution of A1Rs in the human striatum described herein is similar to previous reports of age-related decreases in dopamine D1 and D2 receptors. Unlike A1Rs, however, this study suggests that the distribution of A(2A) Rs does not change with age.

Whole-body distribution and brain tumor imaging with (11)C-4DST: a pilot study.

UNLABELLED: Recently, we developed [methyl-(11)C]4'-thiothymidine ((11)C-4DST) as an in vivo cell proliferation marker. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain tumor imaging of (11)C-4DST in humans. METHODS: Multiorgan biodistribution and radiation dosimetry of (11)C-4DST were assessed in 3 healthy humans, who underwent 2-h whole-body PET scanning. Radiation dosimetry was estimated from the residence times of source organs using the OLINDA program. Six brain tumor patients underwent dynamic (11)C-4DST scans with arterial blood sampling. These patients were also evaluated with (11)C-methionine PET on the same day (n = 4) as, or 3 wk before (n = 2), (11)C-4DST PET studies. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. Breakdown of the blood-brain barrier in tumor tissue was confirmed by gadolinium-enhanced T1-weighted MRI. RESULTS: There were no serious adverse events in any subjects at any time during the study period. (11)C-4DST PET demonstrated selective uptake in the bone marrow, which has a high rate of proliferation. In addition, high-level uptake was also seen in the liver. The highest absorbed organ dose was in the urinary bladder wall (17.6 µGy/MBq). The estimated effective dose for (11)C-4DST was 4.2 µSv/MBq. (11)C-4DST showed little uptake in normal brain tissues, resulting in low background activity for imaging of brain tumors. In contrast, (11)C-4DST PET demonstrated rapid uptake in aggressive tumor masses, whereas no signal of (11)C-4DST was seen in clinically stable disease in which (11)C-methionine uptake was high. The distribution pattern of (11)C-methionine in tumor regions was not always identical to that of (11)C-4DST. Analysis of plasma samples by high-performance liquid chromatography indicated that more than 60% of the radioactivity was present as unchanged (11)C-4DST at 20 min. CONCLUSION: The initial findings of the present study in a small group of patients indicated that (11)C-4DST PET is feasible for imaging of brain tumors. Dosimetry and pharmacologic safety were acceptable at the dose required for adequate PET images.

Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans.

INTRODUCTION: 4-[(11)C]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([(11)C]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping α(7) nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [(11)C]CHIBA-1001 in humans and compared the results with those obtained in mice. METHODS: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [(11)C]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. RESULTS: In humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 µSv/MBq, and that from mice was much underestimated. CONCLUSION: Effective dose estimates for [(11)C]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dosimetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations.

Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

Occupancy of α7 Nicotinic Acetylcholine Receptors in the Brain by Tropisetron: A Positron Emission Tomography Study Using [(11)C]CHIBA-1001 in Healthy Human Subjects.

OBJECTIVE: Agonists of α7-nicotinic acetylcholine receptors (nAChRs) have been developed as potential therapeutic drugs for neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. Positron emission tomography (PET) is a noninvasive brain imaging technique to measure receptor occupancy in the living human brain. Although much effort has been expended to create specific PET radioligands for α7-nAChRs in the brain, only 4-[(11)C]methylphenyl-1,4-diazabicyclo[3.2.2.]nonane-4-carboxylate ([(11)C]CHIBA-1001) is currently available for clinical studies. In contrast, two 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists, tropisetron and ondansetron, have been used to treat patients with chemotherapy-induced or postoperative nausea and vomiting. Furthermore, tropisetron, but not ondansetron, possesses high affinity for α7-nAChRs. In the present study, we evaluated the receptor occupancy in the human brain after a single oral administration of tropisetron and ondansetron using [(11)C]CHIBA-1001 and PET. METHODS: Two serial dynamic PET scans using [(11)C]CHIBA-1001 in healthy non-smoking male subjects were performed before and after receiving an oral administration of these medications. RESULTS: A single oral administration of tropisetron, but not ondansetron, decreased the total distribution volume of [(11)C]CHIBA-1001 in the human brain. CONCLUSION: This study shows that tropisetron, but not ondansetron, could bind to α7-nAChRs in the human brain after a single oral administration. Therefore, [(11)C]CHIBA-1001 may be a useful PET radioligand to measure the occupancy of α7-nAChRs in the human brain.

Development of PET radiopharmaceuticals and their clinical applications at the Positron Medical Center.

The Positron Medical Center has developed a large number of radiopharmaceuticals and 36 radiopharmaceuticals have been approved for clinical use for studying aging and geriatric diseases, especially brain functions. Positron emission tomography (PET) has been used to provide a highly advanced PET-based diagnosis. The current status of the development of radiopharmaceuticals, and representative clinical and methodological results are reviewed.