PET Applications Research Articles

Implementing a Specialist Integrated Haematological Malignancy Imaging Reporting Paradigm to Lymphoma Radiology Assessment Can Significantly Improve the Quality of Data for Patient Management and Clinical Research

Introduction Comprehensive, accurate assessment by radiologists of PET and CT data is crucial for effective staging, prognostication, response assessment and clinical research in lymphoma. Clinicians require evaluation of disease burden at important nodal and extranodal review sites, review of anatomical sites where toxicity or complications of treatment might be evident, and measurement of parameters specific to lymphoma assessment such as bulk, metabolic SUV and Deauville Score. Ideally, integrated conclusions from multimodal radiological data on staging and treatment response by the radiologist enable appropriate decisions on management to be made at multidisciplinary team meetings and can improve quality of data for clinical research. Methods Hodgkin Lymphoma (HL) and Diffuse Large B-Cell Lymphoma (DLBCL) are the two lymphoma subtypes where there is most published evidence for the application of PET and CT. Key PET and CT parameters deemed clinically important in the management of HL and DLBCL at 3 time points - staging, interim and end of treatment - were identified. These parameters are listed in Figure 1. We performed a retrospective review of PET and CT reports at these 3 time points for 20 cases each of HL and DLBCL, over a 5- year period from 2013-2018, to assess the proportion of reports that included each of these key radiological parameters. Results Analysis of staging scan reports demonstrated that disease stage was not recorded in 5% of HL reports and 35% of DLBCL reports. 90% of HL reports did not include a statement of the number of involved nodal groups. The involved nodal groups were however described in 100% of reports. 90% of HL reports did not state whether there was extranodal involvement of disease, but extranodal sites were described in 60% of cases. 50% of DLBCL reports did not include the number of extranodal sites. A measurement of the largest single lesion was not given in 20% of HL and 30% of DLBCL reports. In 75% of HL reports and 55% of DLBCL reports, it was not stated whether there was evidence of bulk. With regard to cases where mediastinal disease was noted, 100% of HL and 89% of DLBCL reports had no documentation of whether there was evidence of SVC obstruction. In 100% of these cases for both HL and DLBCL, there was no documentation of whether there was evidence of thrombus. In terms of PET reports in HL, analysis of interim and end of treatment (EOT) reports demonstrated that SUV max was not given in 45% of interim and 60% of EOT reports. Mediastinal blood pool activity was not given in 85% of interim and 85% of EOT reports. Liver blood pool activity was not given in 95% of interim and 95% of EOT reports. Deauville score was not stated in 75% of interim and 85% of EOT reports. Response classification was not stated in 15% of interim and 40% of EOT reports. With regard to assessment for potential Bleomycin toxicity, the lung parenchyma was not commented on in 40% of interim and 45% of EOT reports. For DLBCL, SUV max was not given in 71% of interim PET scan reports and 65% of EOT reports. Mediastinal blood pool activity was not given in 86% of interim and 95% of EOT reports. Liver blood pool activity was not given in 100% of interim and 90% of EOT reports. Deauville Score was not given in 71% of interim and 80% of EOT reports. Response classification was not stated in 29% of interim and 15% of EOT reports. Conclusion Our data demonstrates retrospective evidence that a significant proportion of imaging reports in HL and DLBCL lack inclusion of radiological parameters crucial to staging, prognostication and response assessment in lymphoma, and required by clinicians to make appropriate management decisions. We therefore propose the implementation of a reporting framework including the parameters outlined in our study, to improve the quality of image reporting in lymphoma and have a positive impact on patient outcomes. Given that lymphoma imaging increasingly involves the use of multiple modalities, we further propose an integrated, standardised radiology reporting framework, under the title 'Specialist Integrated Haematological Malignancy Imaging Reporting', to improve patient outcomes and benefit clinical research. Disclosures Iyengar: Abbvie: Honoraria; Janssen: Honoraria.

Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER) Methodology for Research and Clinical Brain PET Applications.

Tools for efficient evaluation of amyloid- and tau-PET images are needed in both clinical and research settings. This study was designed to validate a semi-automated image analysis methodology, called Biomarker Localization, Analysis, Visualization, Extraction, and Registration (BLAzER). We tested BLAzER using two different segmentation platforms, FreeSurfer (FS) and Neuroreader (NR), for regional brain PET quantification in participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. 127 amyloid-PET and 55 tau-PET studies with volumetric MRIs were obtained from ADNI. The BLAzER methodology utilizes segmentation of MR images by FS or NR, then visualizes and quantifies regional brain PET data using FDA-cleared software (MIM), enabling quality control to ensure optimal registration and to detect segmentation errors. BLAzER analysis required ∼5 min plus segmentation time. BLAzER using FS segmentation showed strong agreement with ADNI for global amyloid-PET standardized uptake value ratios (SUVRs) (r = 0.9922, p < 0.001) and regional tau-PET SUVRs across all Braak staging regions (r > 0.97, p < 0.001) with high inter-operator reproducibility (ICC > 0.97) and nearly identical dichotomization as amyloid-positive or -negative (2 discrepant cases out of 127). Comparing FS versus NR segmentation with BLAzER, global SUVRs were strongly correlated for amyloid-PET (r = 0.9841, p < 0.001), but were systematically higher (4% on average) with NR, likely due to more inclusion of white matter with NR-defined regions. BLAzER provides an efficient methodology for regional brain PET quantification. FDA-cleared components and visualization of registration reduce barriers between research and clinical applications.

MENTAL AND PHYSICAL ACTIVITY DURING THE 80-MINUTE UPTAKE TIME AFFECTS OFF-TARGET BINDING IN TAU PET SCANS (18F-FTP)

With the application of longitudinal tau PET to track disease progress, identifying factors that cause unwanted signal variability is critical. Many have observed off-target 18F-FTP tau PET signal both inside and outside of the brain, including in the basal ganglia, meninges, cortical bone, and cortical muscles. During the 80-minute uptake period, no standard participant activity recommendations are given, and participants may engage in various activities prior to scanning. In this study, we assessed whether mental and physical activity during the uptake time correlated with tau PET signal. We administered a brief questionnaire to 136 participants after their PET scan asking about their mental and physical activities during the 80-minute uptake time. Our survey asked about activities that could affect perfusion, including conversation, reading, listening to music, watching videos, internet use, sleeping, walking, and food/liquid intake. Two independent scan readers measured predetermined off-target regions outside of the brain including: retina, ocular muscle, sinus, jaw muscles (masseter, pterygoid, temporalis), pituitary gland, and cortical bone/dura (superior, inferior-anterior, inferior-posterior positions). Within-brain atlas-based regional measurements were also conducted. Linear regression models were used to assess the relationship between participant's activities and subsequent tau uptake (SUV and SUVR). Participants who reported sleeping during the uptake time had 17% (average) higher tau SUVs in extraocular muscle and cortical bone regions, while participants who reported walking had about 15% lower SUVs (p<0.001 for both activities). In multiple medial-temporal brain regions, walking had a clinically-relevant effect of increasing SUVR by ≈5%. We verified that the proportions of clinical impairment were not significantly different between the walking/sleeping yes/no groups.

Performance Characterization of MPPC Modules for TOF-PET Applications

PET detectors commonly feature large numbers of multipixel photon counters (MPPCs), requiring data acquisition systems with significant signal multiplexing or using application specific integrated circuits (ASICs) for independent MPPC readout. We evaluate here two Hamamatsu C13500-4075LC-12 detector modules designed for time-of-flight (TOF) PET. Each module has a 12 $ {\times }$ 12 lutetium fine silicate crystal array (4.2 $ {\times }$ 4.2 $ {\times }$ 20 mm3) one-to-one coupled to a 12 $ {\times }$ 12 array of 4 mm MPPCs. Each detector has 8 18-channel ASICs utilizing time-over-threshold (ToT) readout. At low event rates, the detectors have full-width at half-maximum (FWHM) energy resolution of 11.8%±0.4%, measured in linearized energy spectra, and 275 ps FWHM coincidence timing resolution (CTR) using energy window of ±1 photopeak FWHM. The 511 keV photopeak amplitude in the ToT spectrum changed 0.24%/°C. There was <10% event loss up to 1450 kcps/detector. From count rates of 35–1450 kcps the 511 keV photopeak position varied by 1.2%, while photopeak FWHM in the ToT spectra increased by 54%, from 5.8% to 9.0%, corresponding to energy resolution changing from 11.8% to approximately 18.0%. Over this count rate range the CTR varied from 285 to 435 ps FWHM. The TOF-PET module performance suggests they are well suited to use in whole-body PET applications.

Application of 18F-FDOPA PET and Magnetic Resonance Spectroscopy (MRS) With HCV and PD

Application of 18F-FDOPA PET and Magnetic Resonance Spectroscopy (MRS) With HCV and PD

Light emission from treated surfaces of poly (ethylene terephthalate).

There has been considerable interest in poly (ethylene terephthalate) (PET) as an undoped scintillation material for charged particle detections. However, light emission from exposed surfaces is limited by the high refractive index. Here, we show the potential applications of surface-treated PET for radioactive contamination inspections. The two large-area surfaces of three 140-mm × 72-mm × 1-mm plates cut from injection-molded PET were treated in three ways: both polished surfaces, one polished and the other roughened (thus, two different entrance faces), and both roughened surfaces. Transmission spectra were acquired to characterize the responses at the PET surfaces by external light. Transmittances were decreased by roughened surfaces; the effect was dominant for short wavelengths, and the transmittance at the emission maximum was less than 1% when both surfaces were roughened. A portable model system, where smeared filter papers or smeared cotton buds were inspected for charged particle detection, was fabricated to characterize the responses at the PET surfaces by internal light. Count rates for a 241Am radioactive source and a 90Sr radioactive source were increased by the roughened surfaces; count rates when both surfaces were roughened were, respectively, 3.7 and 2.1 times those when both surfaces were polished. Thus, the model system responded well to alpha and beta particles via the PET surface treatments. We revealed that the roughened surfaces diffused light emissions by refraction and bent incident angle at the next boundary surface by reflection. In addition, a strong correlation between increased count rates and decreased transmittances was found via the surface treatments. This knowledge will guide the use of PET in future radiation management.

PET/CT for Patients With Breast Cancer: Where Is the Clinical Impact?

OBJECTIVE. FDG PET/CT affects the management of patients with breast cancer in multiple settings, including initial staging, treatment response assessment, and evaluation of suspected recurrence. This article reviews the strengths and weaknesses of FDG PET/CT for the staging of the primary breast lesion, axillary and extraaxillary nodal metastases, and distant metastases. The utility of FDG PET/CT for measuring breast cancer treatment response is appraised and compared with other imaging modalities. The role that tumor histologic type may have on PET/CT interpretation is also discussed. CONCLUSION. Although FDG PET/CT is currently the PET modality with the greatest effect on clinical management of patients with breast cancer, novel radiotracers and imaging systems continue to broaden the application of PET for patients with breast cancer. National Comprehensive Cancer Network guidelines for FDG PET/CT for patients with breast cancer are reviewed. Emphasis is given where FDG PET/CT has shown clinical effect.

PET imaging in renal cancer.

Worldwide, over 400 000 new cases of kidney cancer were diagnosed and over 175 000 deaths anticipated in 2018. It is ranked as the 14th most common cancer in women and 9th most common in men. Imaging is important for initial detection, staging, and monitoring to assist treatment planning, but conventional anatomic imaging is limited. Although functional PET/CT has proven helpful in the diagnosis and management of many cancers, its value in renal cell carcinoma (RCC) is still in evolution. FDG is probably the most useful radiotracer in RCC, although CAIX imaging can be helpful in clear cell RCC. Current research on PET imaging agents in RCC including 89Zr bevacizumab, 89Zr geruntuximab, 18F fluoro-L-thymidine (FLT), prostate-specific membrane antigen (PSMA), 11C choline, 18F sodium fluoride (NaF), and18F fluorodeoxyglucose (FDG) have shown some interesting results for detection and prognosis of the disease. Many innovative radiotracers have been tested in RCC, but robust differentiation of primary disease from normal parenchyma remains elusive for almost all of them. The metastatic setting and response to therapy for this cancer are more favorable PET applications. Continued research in promising molecular tracers will hopefully advance both diagnostic and therapeutic strategies to ultimately eradicate RCC.

Development and evaluation of a double-plane detector system for multi-radionuclide imaging

To develop a multi-radionuclide imaging system with a flexible and compact structure that has a potential for breast and other applications, and to evaluate its performances under both positron emission tomography and single photon emission imaging conditions. The plane detector was composed of 5 × 6 blocks with an effective detection area of 168.6 mm × 202.4 mm. Each block consisted of a 16 × 16 LYSO array. The pixel size is 1.9 mm × 1.9 mm × 15 mm. An 8 × 8 silicon photomultiplier (SiPM) array with SensL’s C-30035 sensors was coupled to the LYSO array, separated by a 1.5-mm-thick glass. To minimize the influence of temperature on the detector, the active part of the front-end electronics was kept away from SiPMs. Self-designed data acquisition system and reconstruction software were utilized to evaluate the performances of the whole system. All the blocks had excellent pixels identification. An average energy resolution of 11.39% for 511 keV and 21.37% for 140 keV was obtained. In the PET mode, the best spatial resolution was better than 2 mm and the system sensitivity reached up to 11.05% at 60 mm distance. In the single photon emission imaging mode, a spatial resolution better than 3 mm was obtained. The results indicated that the system has a good overall performance and can be used in breast imaging and other general PET applications. It also has the potential to be used for single photon emission imaging. In pursuit of a better spatial resolution of cross-plane, PSF and DOI technology will be developed in the next work. For specific applications, further improvement of the detector system such as performance evaluation with phantoms will be carried out.

On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling

IntroductionIndium-111 when formulated as indium-111 oxine remains the gold standard for long term cell tracking, whereas radiometals for improved PET applications still have to be established. We here describe the on-cartridge formation of gallium-68, zirconium-89 and copper-64 complexes in small volumes suitable for cell labelling, including labelling of red blood cells (RBC) and white blood cells (WBC) and their biological evaluation in vivo. MethodsSmall volumes (1–2 mL) of tracers (oxine, tropolone) were directly prepared on an anion exchange cartridge (Sep-Pak QMA). Cells were radiolabelled and the labelling efficiency and efflux were evaluated. The in vivo biodistribution of copper-64-labelled WBC using [64Cu][Cu(oxinate)2] and [64Cu][Cu(tropolonate)2] was monitored in an infection and inflammation animal model using BALB/c mice. ResultsOn-cartridge concentration of gallium-68, zirconium-89 and copper-64 enabled formation of oxine and tropolone tracers in small volumes with good yields (≥50%) and quality (extraction ≥90%). Prepared tracers radiolabelled the RBC comparable to indium-111 tracers and in vivo biodistribution of copper-64 labelled WBC showed clear accumulation of cells at the site of infection and inflammation. ConclusionsThis on-cartridge preparation method enables simple formation of various PET tracers for cell radiolabelling. Zirconium-89 and copper-64 tracers radiolabelled cells with sufficient stability. Due to their longer half-life this approach could be promising for routine applications where longer evaluation periods for cell tracking are needed. Advances in knowledge and implications for patient careThis novel approach for on-cartridge concentration and preparation of oxine and tropolone precursors with different positron emitters, in small volume and suitable pH, offers a versatile tool towards cell labelling for preclinical and clinical PET applications.

Experimental characterization of the TOFPET2 ASIC

We present the experimental characterization of the TOFPET2, a readout and digitization ASIC for radiation detectors using Silicon Photomultipliers. The circuit is designed in CMOS 110 nm technology, has 64 independent channels and is optimized for time-of-flight measurement in PET or other applications. The chip has quad-buffered TDCs and charge integration QDCs in each channel. The Coincidence Time Resolution (CTR) of 511 keV photon pairs from a 22Na point source measured with 2 × 2 × 3 mm3 LSO:Ce crystals co-doped with 0.2% Ca is 118 and 119 ps FWHM when using respectively the SiPMs NUVHD 40um from Fondazione Bruno Kessler (FBK) and the S14160-3050HS MPPC from Hamamatsu Photonics (HPK). The energy resolution obtained for the 511keV photopeak is 10.5 and 12% FWHM when using respectively the SiPMs PM3325-WB from KETEK and the QFBR-S4N44P164S from Broadcom Inc.

Synthesis of [18F]Favipiravir and Biodistribution in C3H/HeN Mice as Assessed by Positron Emission Tomography

Favipiravir (T705; 6-fluoro-3-hydroxypyrazine-2-carboxamide) is a pyrazine analog that has demonstrated potent antiviral activity against a broad spectrum of viruses in multiple in vivo disease models. To better understand the compounds anti-viral activity, assessment of the drug’s biodistribution and kinetics in vivo may lend insight into how best to evaluate the compound efficacy preclinically and to contribute to the design of clinical studies to take into account the compound’s pharmacokinetic distribution and kinetics. In the current study, a method for synthesis of [18F]favipiravir was developed and the biodistribution in mice naïve to and pre-dosed with favipiravir was assessed by PET and gamma counting of tissue samples. Fluorine-18 labeling of favipiravir was achieved in a one-pot, two-step synthesis using a commercially available precursor, methyl-5-chloroisoxazolo[4,5-b]pyrazine-3-carboxylate, with an overall radiochemical yield of 15–24%, a molar activity of 37–74 GBq/µmol in a 70 minute synthesis time. [18F]favipiravir tissue uptake and distribution was similar in naïve and pre-dosed mice; however, in the pre-dosed animals plasma clearance was more rapid and tissue clearance appeared to be prolonged. In conclusion, application of PET to the evaluation of favipiravir has demonstrated the importance of dosing regimen on the distribution and tissue uptake and clearance of the molecule. Favipiravir is cleared through the kidney as previously reported but the liver and intestinal excretion may also play an important role in compound elimination. Measurement of the tissue uptake of favipiravir as determined by PET may be a more important indicator of a compound’s potential efficacy than purely monitoring plasma parameters such as viremia and drug levels.

Imagerie du cancer de la prostate oligométastatique, le point de vue du médecin nucléaire

By virtue of its functional approach and the good resolution of the resulting images, PET fused with CT or MRI appears to be the currently most promising imaging modality for detecting and counting cancer metastases. When the number of metastases is limited, the extension is called oligometastatic, opening the way to a targeted therapy (in particular stereotactic radiotherapy) on the few secondary lesions. This approach has been particularly developed recently in prostate cancer (PC). PET/CT imaging has great potential for the characterisation of PC as oligometastatic, on the one hand, by detecting metastases at an early stage and, on the other hand, by avoiding to apply to PCs that are in fact polymetastatic an oligometastatic-based-management that would be ineffective and would delay starting the appropriate therapy. This article illustrates this new application of PET using various PET tracers either suitable for routine PC imaging, such as sodium fluoride (18F), fluorocholine (18F), fluciclovine (18F) or which have not yet been granted a MA, such as 68Ga or 18F-labeled ligands of prostate-specific antigen.

Selection of abstracts from the scientific sessions of the Society of Nuclear Medicine and Molecular Imaging, Philadelphia PA June 23–26, 2018

This mini-review highlights cardiovascular studies that were presented during the 2018 Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting in Philadelphia. The aim of this review is to inform readers about several noteworthy studies reported at the meeting. Although cardiovascular application of PET and SPECT are not the primary focus of the SNMMI, several scientific teams working in this field presented their latest scientific findings at this meeting. The review therefore aims to inform the readers who did not attend the SNMMI annual meeting about some interesting new concepts presented this year at the conference.

PSMA PET applications in the prostate cancer journey: from diagnosis to theranostics.

The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed.

Experimental test and characterization of BASIC64, a new mixed-signal front-end ASIC for SiPM detectors

BASIC64 is a new multichannel front-end ASIC for Silicon photomultiplier detectors used in PET systems. The preamplifier input resistance is ∼ 50 Ω , low enough not to further affect the slope of incoming current pulses, already plagued by the presence of stray series inductance . For each channel, the signals generated by the detector follow two parallel processing paths, respectively for timing and energy measurements. The results of experimental test and characterization for timing accuracy and gain linearity are presented and confirm that BASIC64 is suitable for PET applications. • Design and characterization of a SiPM readout front-end with a 50 W input resistance. • Linearity and jitter evaluation in many operative conditions. • The ASIC is suitable for PET applications.

Production of 15O for Medical Applications via the 16O(γ,n)15O Reaction.

15O (half-life, 122 s) is a useful radionuclide for PET applications. Current production of 15O typically makes use of the 14N(d,n)15O, 15N(p,n)15O, or 16O(p,pn)15O reactions using an accelerator. A novel approach for the production of 15O is via the 16O(γ,n)15O reaction using an electron linear accelerator. Photonuclear reactions using an electron linear accelerator may allow for feasible and economical production of 15O compared with the current methods. Methods: In this work, experiments using a repurposed Clinac were conducted using oxygen-containing alumina as a target material to study the production rate of 15O. Additional studies were conducted using a water target cell. Simulations using Geant4 were conducted to predict the activity and power dissipation in the target. Results: Bremsstrahlung radiation from the electron beam, and consequently 15O production via photonuclear reactions, is enhanced when a high-Z material, tungsten, is placed in front of the target. The alumina irradiations provided preliminary data to optimize the beam parameters and target configuration. The optimal thickness of tungsten was 1.4 mm for both the simulated and the measured studies of alumina. Simulations of irradiated water targets showed that tungsten thicker than 1.4 mm resulted in fewer photons available to activate the water; thus, a higher current was required to achieve a fixed dose. Alternatively, for a constant tungsten thickness, more power was deposited in the target with increasing beam energy, requiring a lower current to achieve a fixed dose. Actual irradiations of a water target yielded a quantity of 15O in the water that was consistent with expectations based on irradiations of alumina. Conclusion: Several parameters should be considered regarding the photonuclear production of 15O for an average patient dose of 1,850 MBq (50 mCi) in 10 mL. This work illustrates a variety of machine parameters capable of achieving a reasonable patient dose. Our simulations show that the power deposited in the target for these parameters is less than that in commercially operated cyclotron targets for the production of 18F. Thus, this work demonstrates that the photonuclear production of 15O may be a new production path for this useful radionuclide.

Application and prospect of PET in cancer-related cognitive impairment studies

With the increasing number of cancer survivals, more attention has been paid to the cancer-related cognitive impairment (CRCI). It is urgent to explore the mechanism of CRCI as well as early intervention and relieving of such diseases. This review summarizes the application of PET in neuropsychology and cognitive impairment diseases. The advanced research progress and prospects of PET in CRCI are also introduced. Key words: Cognition disorders; Neoplasms; Positron-emission tomography; Trends

An improved time over threshold method using bipolar signals

The time over threshold (TOT) method has been recently proposed as a signal processing method used to calculate time and energy information by measuring the pulse arrival time and pulse duration over a preset threshold. Although TOT has been reported as an effective method for front end readout in PET applications, it has several limitations, including its non-linearity, lower dynamic range, and a trade-off between energy resolution and coincidence resolving time (CRT). In this study, we propose a novel design we developed to improve performance with regard to these problems occurring in the conventional TOT by employing a bipolar signal and two comparators. Using a high frequency CR shaping filter, a detected signal was converted into a bipolar signal, and the positive pulse of the converted bipolar signal had a fast rising time, while the negative pulse had a linear slope. The bipolar TOT circuit was composed of a preamplifier, a CR shaping filter, and two comparators. The PET detector was composed of a single LYSO coupled with 4 × 4 SiPM arrays, a bipolar TOT circuit, and an FPGA based TDC. And this was constructed to evaluate the performance of the proposed bipolar TOT method. A 16-ch PET detector module consisting of a 4 × 4 array LYSO coupled to a 4 × 4 SiPM arrays, an Anger logic discretized positioning circuit, and a 4-ch bipolar TOT circuit was also constructed to evaluate the functionality of the bipolar TOT method for PET applications. The pulse height resolution and CRT were measured using both the bipolar TOT method and the conventional TOT method. While the bipolar TOT method provided a similar pulse height resolution (10.4% ± 0.1%), the integral non-linearity (1.4%) and CRT (168 ± 4 ps) measured using the bipolar TOT method were greatly improved compared to those (17.2% and 258 ± 15 ps, respectively) measured with the conventional TOT method. The positions of the crystals were clearly identified, as seen in the flood histogram acquired using the 4-ch bipolar TOT circuit. The measured average pulse height resolution and average CRT for the 16-ch detector module were 11.5% ± 0.2% and 516 ± 24 ps. The results obtained in this study indicate that the bipolar TOT method requiring a relatively small number of electronic components could effectively improve the CRT, linearity and dynamic range. Furthermore, they also demonstrated the extendibility allowing the development of a PET system that consists of a large number of detectors.

Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer.

The high diagnostic potential of 64Cu-PSMA PET-CT imaging was clinically investigated in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local disease. The aim of our study is to assess the uptake behavior in the clinical setting of 64Copper Prostate-Specific Membrane Antigen (64Cu PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) in prostate cancer. A retrospective study was performed in 23 patients with intermediate, high risk and progressive disease at primary staging of prostate cancer. All patients underwent 64Cu-PSMA PET. Overall, 250MBq (4MBq per kg bodyweight, range 230-290MBq) of 64Cu-NODAGA PSMA was intravenously applied. PET images were performed 30min (pelvis and abdomen) and 1-2h post-injection (skull base to mid-thigh). Maximum standardized uptake values (SUVmax) were measured in the organs with high physiological uptake such as liver and kidney, and, additionally, background activity was measured in the gluteal area and in suspected tumor lesions using a HERMES workstation. PSMA uptake was detected in prostate bed in nine patients, in six patients in distant metastases (bone, lung and liver) and in nine patients in lymph nodes. Of 23 patients, 5 (20.8%) did not show any focal pathological uptake in the whole body. The number of sites (prostate bed, lymph nodes, distant metastases) with positive PSMA uptake was significantly associated with PSA values before imaging (P=0.0032). The 64Cu PSMA uptake increased significantly from 30min to 1-3h post-injection (Wilcoxon signed rank test, P = 0.002). 64Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.