Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators.

Assessment of the effect of therapy in a rat model of glioblastoma using [18F]FDG and [18F]FCho PET compared to contrast-enhanced MRI.

OBJECTIVE: We investigated the potential of [18F]fluorodeoxyglucose ([18F]FDG) and [18F]Fluoromethylcholine ([18F]FCho) PET, compared to contrast-enhanced MRI, for the early detection of treatment response in F98 glioblastoma (GB) rats. METHODS: When GB was confirmed on T2- and contrast-enhanced T1-weighted MRI, animals were randomized into a treatment group (n = 5) receiving MRI-guided 3D conformal arc micro-irradiation (20 Gy) with concomitant temozolomide, and a sham group (n = 5). Effect of treatment was evaluated by MRI and [18F]FDG PET on day 2, 5, 9 and 12 post-treatment and [18F]FCho PET on day 1, 6, 8 and 13 post-treatment. The metabolic tumor volume (MTV) was calculated using a semi-automatic thresholding method and the average tracer uptake within the MTV was converted to a standard uptake value (SUV). RESULTS: To detect treatment response, we found that for [18F]FDG PET (SUVmean x MTV) is superior to MTV only. Using (SUVmean x MTV), [18F]FDG PET detects treatment effect starting as soon as day 5 post-therapy, comparable to contrast-enhanced MRI. Importantly, [18F]FDG PET at delayed time intervals (240 min p.i.) was able to detect the treatment effect earlier, starting at day 2 post-irradiation. No significant differences were found at any time point for both the MTV and (SUVmean x MTV) of [18F]FCho PET. CONCLUSIONS: Both MRI and particularly delayed [18F]FDG PET were able to detect early treatment responses in GB rats, whereas, in this study this was not possible using [18F]FCho PET. Further comparative studies should corroborate these results and should also include (different) amino acid PET tracers.

Validation of hepatobiliary transport PET imaging in liver function assessment: Evaluation of 3ß-[18F]FCA in mouse models of liver disease.

Recently, our research group reported on the development of 3ß-[18F]Fluorocholic acid (3ß-[18F]FCA), a 18F labeled bile acid to detect drug interference with the bile acid transporters (drug-induced cholestasis). It was hypothesized that 3ß-[18F]FCA could also be used as a non-invasive tool to monitor (regional) liver function in vivo in different liver diseases through altered expression of bile acid transporters. METHODS: Hepatobiliary transport of 3ß-[18F]FCA was evaluated in four murine liver disease models. Acute liver injury was induced by oral gavage of an acetaminophen (APAP) overdose (300 mg/kg). Chronic cholangiopathy and non-alcoholic steatohepatitis (NASH) were induced by feeding mice 3,5-diethoxycarbonyl- 1,4-dihydrocollidine (DDC) diet or methionine and choline deficient (MCD) diet, respectively. Hepatocellular carcinoma (HCC) was evoked by intraperitoneal injection of 35 mg/kg diethylnitrosamine (DEN) once a week for 23 weeks. Gene expression of the murine bile acid transporters was determined by RT-qPCR. RESULTS: Hepatobiliary transport of 3ß-[18F]FCA was not significantly altered after an APAP overdose. Mice fed the DDC or MCD diet showed impaired transport of 3ß-[18F]FCA compared to baseline, which was associated with altered expression of the bile acid transporters ntcp, oatp4 and mrp2. After recovery from DDC- and MCD-induced liver injury, 3ß-[18F]FCA parameters returned to baseline. Global hepatobiliary transport of 3ß-[18F]FCA in HCC bearing mice was not significantly different compared to control mice. However, HCC lesions showed reduced hepatic uptake of the tracer (tumor-to-background: 0.45 ±â€¯0.13), which was in line with decreased in expression of basolateral bile acid uptake transporters nctp and oatp4 in tumor tissue. CONCLUSION: 3ß-[18F]FCA is a useful tool to assess and longitudinally follow-up liver function in several mouse models for liver diseases that are associated with altered expression of the bile acid transporters. These results point towards the (pre)clinical utility of 3ß-[18F]FCA as a PET tracer to monitor altered liver functionality in patients with chronic liver diseases.

Phase I Study of 68Ga-HER2-Nanobody for PET/CT Assessment of HER2 Expression in Breast Carcinoma.

UNLABELLED: Human epidermal growth factor receptor 2 (HER2) status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression between primary tumor and metastasis has repeatedly been described, resulting in the need to reassess HER2 status during the disease course. To avoid repeated biopsy with potential bias due to tumor heterogeneity, Nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies, which are derived from unique heavy-chain-only antibodies, are the smallest antigen-binding antibody fragments and have ideal characteristics for PET imaging. The primary aims were assessment of safety, biodistribution, and dosimetry. The secondary aim was to investigate tumor-targeting potential. METHODS: In total, 20 women with primary or metastatic breast carcinoma (score of 2+ or 3+ on HER2 immunohistochemical assessment) were included. Anti-HER2-Nanobody was labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average, 107 MBq). PET/CT scans for dosimetry assessment were obtained at 10, 60, and 90 min after administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor-targeting potential was assessed in primary and metastatic lesions. RESULTS: No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1 h after injection. Uptake was seen mainly in the kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall, with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above the background level was demonstrated in most identified sites of disease. Primary lesions were more variable in tracer accumulation. CONCLUSION: (68)Ga-HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in the kidneys, liver, and intestines but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared with normal surrounding tissues, and warrants further assessment in a phase II trial.

Collimator design for a multipinhole brain SPECT insert for MRI.

PURPOSE: Brain single photon emission computed tomography (SPECT) imaging is an important clinical tool, with unique tracers for studying neurological diseases. Nowadays, most commercial SPECT systems are combined with x-ray computed tomography (CT) in so-called SPECT/CT systems to obtain an anatomical background for the functional information. However, while CT images have a high spatial resolution, they have a low soft-tissue contrast, which is an important disadvantage for brain imaging. Magnetic resonance imaging (MRI), on the other hand, has a very high soft-tissue contrast and does not involve extra ionizing radiation. Therefore, the authors designed a brain SPECT insert that can operate inside a clinical MRI. METHODS: The authors designed and simulated a compact stationary multipinhole SPECT insert based on digital silicon photomultiplier detector modules, which have shown to be MR-compatible and have an excellent intrinsic resolution (0.5 mm) when combined with a monolithic 2 mm thick LYSO crystal. First, the authors optimized the different parameters of the SPECT system to maximize sensitivity for a given target resolution of 7.2 mm in the center of the field-of-view, given the spatial constraints of the MR system. Second, the authors performed noiseless simulations of two multipinhole configurations to evaluate sampling and reconstructed resolution. Finally, the authors performed Monte Carlo simulations and compared the SPECT insert with a clinical system with ultrahigh-resolution (UHR) fan beam collimators, based on contrast-to-noise ratio and a visual comparison of a Hoffman phantom with a 9 mm cold lesion. RESULTS: The optimization resulted in a stationary multipinhole system with a collimator radius of 150.2 mm and a detector radius of 172.67 mm, which corresponds to four rings of 34 diSPM detector modules. This allows the authors to include eight rings of 24 pinholes, which results in a system volume sensitivity of 395 cps/MBq. Noiseless simulations show sufficient axial sampling (in a Defrise phantom) and a reconstructed resolution of 5.0 mm (in a cold-rod phantom). The authors compared the 24-pinhole setup with a 34-pinhole system (with the same detector radius but a collimator radius of 156.63 mm) and found that 34 pinholes result in better uniformity but a worse reconstruction of the cold-rod phantom. The authors also compared the 24-pinhole system with a clinical triple-head UHR fan beam system based on contrast-to-noise ratio and found that the 24-pinhole setup performs better for the 6 mm hot and the 16 mm cold lesions and worse for the 8 and 10 mm hot lesions. Finally, the authors reconstructed noisy projection data of a Hoffman phantom with a 9 mm cold lesion and found that the lesion was slightly better visible on the multipinhole image compared to the fan beam image. CONCLUSIONS: The authors have optimized a stationary multipinhole SPECT insert for MRI and showed the feasibility of doing brain SPECT imaging inside a MRI with an image quality similar to the best clinical SPECT systems available.