Development of a novel phantom for tau PET imaging.

PURPOSE: The cortical uptake of tau positron emission tomography (PET) tracers corresponds to the Braak stage and reflects the distribution and progression of tau neurofibrillary tangles. The present study aimed to develop and validate the basic performance of a novel tau PET phantom, as well as to establish standard test procedures and analytical methods. METHODS: The tau PET phantom consisted of a brain simulation section simulated medial temporal lobe region and resolution and uniformity sections. The brain simulation section and hot rods and uniformity section contained 4 and 2 kBq/mL of 18F, respectively and images were acquired three times for 20 min with a PET/CT scanner. The resolution section was visually assessed with two sets of hot and cold rods. Recovery coefficients (RCs) as a quantitative value and coefficient of variation (CV) as image noise were determined based on the brain simulation and the uniformity section, respectively. RESULTS: Preparation of activity in the phantom was repeatable among three measurements. The quality of images in the brain simulation and uniformity section with the rods was good. The 5- or 6-mm rods were detected separately. The mean RCs calculated based on the VOI template were between 0.75 and 0.83. The CV at the center slice of uniformity section was 5.54%. CONCLUSIONS: We developed a novel tau PET phantom to assess quantitative value, image noise, and detectability and resolution from brain simulation section, uniformity section, and rods, respectively. This phantom will contribute to the standardization and harmonization of tau PET imaging.

A quantitative assessment of Geant4 for predicting the yield and distribution of positron-emitting fragments in ion beam therapy.

Objective.To compare the accuracy with which different hadronic inelastic physics models across ten Geant4 Monte Carlo simulation toolkit versions can predict positron-emitting fragments produced along the beam path during carbon and oxygen ion therapy.Approach.Phantoms of polyethylene, gelatin, or poly(methyl methacrylate) were irradiated with monoenergetic carbon and oxygen ion beams. Post-irradiation, 4D PET images were acquired and parent11C,10C and15O radionuclides contributions in each voxel were determined from the extracted time activity curves. Next, the experimental configurations were simulated in Geant4 Monte Carlo versions 10.0 to 11.1, with three different fragmentation models-binary ion cascade (BIC), quantum molecular dynamics (QMD) and the Liege intranuclear cascade (INCL++) - 30 model-version combinations. Total positron annihilation and parent isotope production yields predicted by each simulation were compared between simulations and experiments using normalised mean squared error and Pearson cross-correlation coefficient. Finally, we compared the depth of the maximum positron annihilation yield and the distal point at which the positron yield decreases to 50% of peak between each model and the experimental results.Main results.Performance varied considerably across versions and models, with no one version/model combination providing the best prediction of all positron-emitting fragments in all evaluated target materials and irradiation conditions. BIC in Geant4 10.2 provided the best overall agreement with experimental results in the largest number of test cases. QMD consistently provided the best estimates of both the depth of peak positron yield (10.4 and 10.6) and the distal 50%-of-peak point (10.2), while BIC also performed well and INCL generally performed the worst across most Geant4 versions.Significance.The best predictions of the spatial distribution of positron annihilations and positron-emitting fragment production along the beam path during carbon and oxygen ion therapy was obtained using Geant4 10.2.p03 with BIC or QMD. These version/model combinations are recommended for future heavy ion therapy research.

Improved Correlation of 18F-Flortaucipir PET SUVRs and Clinical Stages in the Alzheimer Disease Continuum with the MUBADA/PERSI-Based Analysis.

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18F-flortaucipir PET imaging is expected to visualize progression through the stages of AD, for which quantitative assessment is essential. Two measurement methods, statistically defined multiblock barycentric discriminant analysis (MUBADA)/parametric estimation of reference signal intensity (PERSI) and anatomically defined tau meta-volume of interest (VOI)/cerebellar gray matter (CGM) for SUV ratio (SUVR), were compared in this study to assess their relationship to AD clinical stage using 2 open multicenter PET databases. Methods: Data were selected for 106 cases from 2 databases, AMED Preclinical AD study (AMED-PRE) (n = 15) and Alzheimer Disease Neuroimaging Initiative 3 (n = 91). The data of the participants were categorized into 4 groups based on the clinical criteria. Tau PET imaging was conducted using 18F-flortaucipir, and the 2 SUVR measurement methods, MUBADA/PERSI and tau meta-VOI/CGM, were compared among different clinical categories: amyloid-negative cognitively normal, preclinical AD, amyloid-negative mild cognitive impairment (MCI), and amyloid-positive MCI. Results: Significant differences were found between cognitively normal and preclinical AD, as well as between cognitively normal and amyloid-positive MCI and between amyloid-negative MCI and -positive MCI in SUVR derived by MUBADA/PERSI, whereas SUVR by tau meta-VOI/CGM did not provide significant differences between any pair. The tau meta-VOI/CGM method consistently provided higher SUVRs and larger individual variations than MUBADA/PERSI, with a mean SUVR difference of 0.136 for the studied databases. Conclusion: MUBADA/PERSI provided the SUVR of 18F-flortaucipir uptake with better association with the clinical severity of the AD continuum and with smaller variability. The results support the usefulness of MUBADA/PERSI as a quantitative measure of 18F-flortaucipir uptake in multicenter studies using different PET systems and scanning methods. However, limitations of the study include the small sample size and the unbalanced distribution among clinical categories in the AMED Preclinical AD study database.

[Accuracy of Injection Dose of Amyloid PET Agent Using Radiopharmaceutical Activity Suppliers].

PURPOSE: This study aimed to identify disposable items with low amyloid positron emission tomography (PET) agent radioactivity adsorption for accurate injections using a radiopharmaceutical activity supplier. METHODS: First, we investigated disposable items currently used for amyloid PET agent injection. Next, we measured the residual radioactivity rates of amyloid PET agents on three-way stopcocks, extension tubes, butterfly needles, and indwelling needles to identify disposable items with low radioactivity adsorption. Finally, we evaluated the accuracy of amyloid PET agent injection using the selected disposable items and a radiopharmaceutical activity supplier. RESULTS: The polybutadiene extension tube exhibited a significantly lower residual activity rate than that of the polyvinyl chloride extension tube. Similarly, the indwelling needles showed significantly lower residual activity rate than that of butterfly needles. The dose indicated by a radiopharmaceutical activity supplier was 184.1 MBq, while the dose calibrator measured the radioactivity which flowed into the vial as 170.2 MBq, resulting in an administration accuracy of 8.2%. CONCLUSION: To ensure accurate amyloid PET agent injections, we recommend using polybutadiene extension tubes and indwelling needles due to their lower radioactivity adsorption.

Pre-acquired CT-based attenuation correction with automated headrest removal for a brain-dedicated PET system.

Attenuation correction (AC) is essential for quantitative positron emission tomography (PET) images. Attenuation coefficient maps (µ-maps) are usually generated from computed tomography (CT) images when PET-CT combined systems are used. If CT has been performed prior to PET imaging, pre-acquired CT can be used for brain PET AC, because the human head is almost rigid. This pre-acquired CT-based AC approach is suitable for stand-alone brain-dedicated PET, such as VRAIN (ATOX Co. Ltd., Tokyo, Japan). However, the headrest of PET is different from the headrest in pre-acquired CT images, which may degrade the PET image quality. In this study, we prepared three different types of µ-maps: (1) based on the pre-acquired CT, where namely the headrest is different from the PET system (µ-map-diffHr); (2) manually removing the headrest from the pre-acquired CT (µ-map-noHr); and (3) artificially replacing the headrest region with the headrest of the PET system (µ-map-sameHr). Phantom images by VRAIN using each µ-map were investigated for uniformity, noise, and quantitative accuracy. Consequently, only the uniformity of the images using µ-map-diffHr was out of the acceptance criteria. We then proposed an automated method for removing the headrest from pre-acquired CT images. In comparisons of standardized uptake values in nine major brain regions from the 18F-fluoro-2-deoxy-D-glucose-PET of 10 healthy volunteers, no significant differences were found between the µ-map-noHr and the µ-map-sameHr. In conclusion, pre-acquired CT-based AC with automated headrest removal is useful for brain-dedicated PET such as VRAIN.

Toward standardization of tau PET imaging corresponding to various tau PET tracers: a multicenter phantom study.

OBJECTIVE: Tau positron emission tomography (PET) imaging is a recently developed non-invasive tool that can detect the density and extension of tau neurofibrillary tangles. Tau PET tracers have been validated to harmonize and accelerate their development and implementation in clinical practice. Whereas standard protocols including injected dose, uptake time, and duration have been determined for tau PET tracers, reconstruction parameters have not been standardized. The present study conducted phantom experiments based on tau pathology to standardize quantitative tau PET imaging parameters and optimize reconstruction conditions of PET scanners at four Japanese sites according to the results of phantom experiments. METHODS: The activity of 4.0 and 2.0 kBq/mL for Hoffman 3D brain and cylindrical phantoms, respectively, was estimated from published studies of brain activity using [18F]flortaucipir, [18F]THK5351, and [18F]MK6240. We developed an original tau-specific volume of interest template for the brain based on pathophysiological tau distribution in the brain defined as Braak stages. We acquired brain and cylindrical phantom images using four PET scanners. Iteration numbers were determined as contrast and recover coefficients (RCs) in gray (GM) and white (WM) matter, and the magnitude of the Gaussian filter was determined from image noise. RESULTS: Contrast and RC converged at ≥ 4 iterations, the error rates of RC for GM and WM were < 15% and 1%, respectively, and noise was < 10% in Gaussian filters of 2-4 mm in images acquired using the four scanners. Optimizing the reconstruction conditions for phantom tau PET images acquired by each scanner improved contrast and image noise. CONCLUSIONS: The phantom activity was comprehensive for first- and second-generation tau PET tracers. The mid-range activity that we determined could be applied to later tau PET tracers. We propose an analytical tau-specific VOI template based on tau pathophysiological changes in patients with AD to standardize tau PET imaging. Phantom images reconstructed under the optimized conditions for tau PET imaging achieved excellent image quality and quantitative accuracy.

A review of harmonization strategies for quantitative PET.

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non-18F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer's disease.

OBJECTIVE: A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese. METHODS: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [18F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [18F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments. RESULTS: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 µGy/MBq) and the urinary bladder (127.3 ± 11.7 µGy/MBq). The effective dose was 26.8 ± 1.4 µSv/MBq. The parent form ([18F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [18F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01). CONCLUSION: The findings supported safety and efficacy of [18F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [18F]MK-6240 were consistent with those for non-Japanese populations. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-194972.

Performance evaluation of VRAIN: a brain-dedicated PET with a hemispherical detector arrangement.

Objective.For PET imaging systems, a smaller detector ring enables less intrinsic spatial resolution loss due to the photon non-collinearity effect as well as better balance between production cost and sensitivity, and a hemispherical detector arrangement is more appropriate for brain imaging than a conventional cylindrical arrangement. Therefore, we have developed a brain-dedicated PET system with a hemispherical detector arrangement, which has been commercialized in Japan under the product name of VRAINTM. In this study, we evaluated imaging performance of VRAIN.Approach.The VRAIN used 54 detectors to form the main hemispherical unit and an additional half-ring behind the neck. Each detector was composed of a 12 × 12 array of lutetium fine silicate crystals (4.1 × 4.1 × 10 mm3) and a 12 × 12 array of silicon photomultipliers (4 × 4 mm2active area) with the one-to-one coupling. We evaluated the physical performance of VRAIN according to the NEMA NU 2-2018 standards. Some measurements were modified so as to fit the hemispherical geometry. In addition, we performed18F-FDG imaging in a healthy volunteer.Main results.In the phantom study, the VRAIN showed high resolution for separating 2.2 mm rods, 229 ps TOF resolution and 19% scatter fraction. With the TOF gain for a 20 cm diameter object (an assumed head diameter), the peak noise-equivalent count rate was 144 kcps at 9.8 kBq ml-1and the sensitivity was 25 kcps MBq-1. Overall, the VRAIN provided excellent image quality in phantom and human studies. In the human FDG images, small brain nuclei and gray matter structures were clearly visualized with high contrast and low noise.Significance.We demonstrated the excellent imaging performance of VRAIN, which supported the advantages of the hemispherical detector arrangement.

Small nuclei identification with a hemispherical brain PET.

BACKGROUND: To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared 18F-fluorodeoxyglucose (FDG) brain images with whole-body PET images. METHODS: Ten healthy male volunteers (aged 22-45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants' age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images. RESULTS: Small nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman's correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET. CONCLUSIONS: This was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET. TRIAL REGISTRATION  : Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086 .

Feasibility of triple gamma ray imaging of10C for range verification in ion therapy.

Objective.In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive15O and11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient's body during ion therapy.Approach.In this work, we focus on investigating the performance of WGI for10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba.Main results.The average spatial resolution and sensitivity for the simulated10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the10C ion beam was measured, and the triple gamma image of10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas.Significance.The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of10C ion beams.

Brain PET motion correction using 3D face-shape model: the first clinical study.

OBJECTIVE: Head motions during brain PET scan cause degradation of brain images, but head fixation or external-maker attachment become burdensome on patients. Therefore, we have developed a motion correction method that uses a 3D face-shape model generated by a range-sensing camera (Kinect) and by CT images. We have successfully corrected the PET images of a moving mannequin-head phantom containing radioactivity. Here, we conducted a volunteer study to verify the effectiveness of our method for clinical data. METHODS: Eight healthy men volunteers aged 22-45 years underwent a 10-min head-fixed PET scan as a standard of truth in this study, which was started 45 min after 18F-fluorodeoxyglucose (285 ± 23 MBq) injection, and followed by a 15-min head-moving PET scan with the developed Kinect based motion-tracking system. First, selecting a motion-less period of the head-moving PET scan provided a reference PET image. Second, CT images separately obtained on the same day were registered to the reference PET image, and create a 3D face-shape model, then, to which Kinect-based 3D face-shape model matched. This matching parameter was used for spatial calibration between the Kinect and the PET system. This calibration parameter and the motion-tracking of the 3D face shape by Kinect comprised our motion correction method. The head-moving PET with motion correction was compared with the head-fixed PET images visually and by standard uptake value ratios (SUVRs) in the seven volume-of-interest regions. To confirm the spatial calibration accuracy, a test-retest experiment was performed by repeating the head-moving PET with motion correction twice where the volunteer's pose and the sensor's position were different. RESULTS: No difference was identified visually and statistically in SUVRs between the head-moving PET images with motion correction and the head-fixed PET images. One of the small nuclei, the inferior colliculus, was identified in the head-fixed PET images and in the head-moving PET images with motion correction, but not in those without motion correction. In the test-retest experiment, the SUVRs were well correlated (determinant coefficient, r2 = 0.995). CONCLUSION: Our motion correction method provided good accuracy for the volunteer data which suggested it is useable in clinical settings.

Marker-less and calibration-less motion correction method for brain PET.

Marker-less head motion correction methods have been well-studied; however, no reports discussing potential issues in positional calibration between a PET system and an external sensor remain limited. In this study, we develop a method for positional calibration between the PET system and an external range sensor to achieve practical head motion correction. The basic concept of the developed method involves using the subject's face model as a marker not only for head motion detection but also for the system positional calibration. The face model of the subject, which can be obtained easily using the range sensor, can also be calculated from a computed tomography (CT) image of the same subject. The CT image, which is acquired separately for attenuation correction in PET, has the same coordinates as the PET image because of the appropriate matching algorithm between CT and PET images. The proposed method was implemented in the helmet-type PET and the motion correction accuracy was assessed quantitatively using a mannequin head. The phantom experiments demonstrated the performance of the developed motion correction method; high-resolution images with no trace of the applied motion were obtained as if no motion was provided. Statistical analysis supported the visual assessment results in terms of the spatial resolution, contrast recovery; uniformity, and the results implied that motion with correction slightly improved image quality compared with the motionless case. The tolerance of the developed method against potential tracking errors had a minimum 10% difference in the amplitude of the rotation angle.

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.

Initial results of a mouse brain PET insert with a staggered 3-layer DOI detector.

Objective.Small animal positron emission tomography (PET) requires a submillimeter resolution for better quantification of radiopharmaceuticals. On the other hand, depth-of-interaction (DOI) information is essential to preserve the spatial resolution while maintaining the sensitivity. Recently, we developed a staggered 3-layer DOI detector with 1 mm crystal pitch and 15 mm total crystal thickness, but we did not demonstrate the imaging performance of the DOI detector with full ring geometry. In this study we present initial imaging results obtained for a mouse brain PET prototype developed with the staggered 3-layer DOI detector.Approach.The prototype had 53 mm inner diameter and 11 mm axial field-of-view. The PET scanner consisted of 16 DOI detectors each of which had a staggered 3-layer LYSO crystal array (4/4/7 mm) coupled to a 4 × 4 silicon photomultiplier array. The physical performance was evaluated in terms of the NEMA NU 4 2008 protocol.Main Results.The measured spatial resolutions at the center and 15 mm radial offset were 0.67 mm and 1.56 mm for filtered-back-projection, respectively. The peak absolute sensitivity of 0.74% was obtained with an energy window of 400-600 keV. The resolution phantom imaging results show the clear identification of a submillimetric rod pattern with the ordered-subset expectation maximization algorithm. The inter-crystal scatter rejection using a narrow energy window could enhance the resolvability of a 0.75 mm rod significantly.Significance.In an animal imaging experiment, the detailed mouse brain structures such as cortex and thalamus were clearly identified with high contrast. In conclusion, we successfully developed the mouse brain PET insert prototype with a staggered 3-layer DOI detector.

Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer.

BACKGROUND: In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery. METHODS: A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations. RESULTS: Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group. CONCLUSIONS: OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.

Monte Carlo simulation of the acquisition conditions for 177Lu molecular imaging of hepatic tumors.

OBJECTIVE: To examine the impact of acquisition time on Lutetium-177 (177Lu) single-photon emission computed tomography (SPECT) images using Monte Carlo simulation. METHODS: A gamma camera simulation based on the Monte Carlo method was performed to produce SPECT images. The phantom was modeled on a NEMA IEC BODY phantom including six spheres as tumors. After the administration of 7.4 GBq of 177Lu, radioactivity concentrations of the tumor/liver at 6, 24, and 72 h after administration were set to 1.85/0.201, 2.12/0.156, and 1.95/0.117 MBq/mL, respectively. In addition, the radioactivity concentrations of the tumor at 72 h after administration varied by 1/2, 1/4, and 1/8 when comparison was made. Acquisition times examined were 1.2, 1.5, 2, 3, 6, and 12 min. To assess the impact of collimators, SPECT data acquired at 72 h after the administration using six collimators of low-energy high-resolution (LEHR), extended low-energy general-purpose (ELEGP), medium-energy, and general-purpose (MEGP-1, MEGP-2, and MEGP-3) and high-energy general-purpose (HEGP) were examined. After prefiltering using a Butterworth filter, projection images were reconstructed using ordered subset expectation maximization. The detected photons were classified into direct rays, scattered rays, penetrating rays, and characteristic X-rays from lead. The image quality was evaluated through visual assessment, and physical assessment of contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR). In this study, the CNR threshold for detectability was assumed to be 5.0. RESULTS: To compare collimators, the highest sensitivity was observed with ELEGP, followed by LEHR and MEGP-1. The highest ratio of direct ray was also observed in ELEGP followed by MEGP-1. In comparison of the radioactivity concentration ratios of tumor/liver, CRC and CNR were significantly decreased with smaller radioactivity concentration ratios. This effect was greater with larger spheres. According to the visual assessment, the acquisition time of 6, 6, and 3 min or longer was required using ELEGP collimator at 6, 24, and 72 h after administration, respectively. Physical assessment based on CNR and CRC also suggested that 6, 6, and 3 min or longer acquisition time was necessary at 6, 24, and 72 h after administration. CONCLUSION: 177Lu-SPECT images generated via the Monte Carlo simulation suggested that the recommended acquisition time was 6 min or longer at 6 and 24 h and 3 min or longer at 72 h after administration.