Prospective Study on the Performance of 18F-DOPA Positron Emission Tomography/Computed Tomography in Patients with Medullary Thyroid Carcinoma

Purpose 18F-DOPA Positron Emission Tomography/Computed Tomography (18F-DOPA PET/CT) is a sensitive functional imaging method (65-75%) for detecting disease localization in medullary thyroid cancer (MTC). We aimed: i) to assess the clinical usefulness of 18F-DOPA PET/CT in patients with MTC and elevated calcitonin (Ctn) and CEA levels and, ii) to evaluate changes in disease management secondary to the findings encountered with this methodology. Methods thirty-six patients with MTC and Ctn levels ≥150 pg/ml were prospectively included. Neck ultrasound, chest contrast-enhanced CT, liver magnetic resonance imaging/ abdominal 3-phase contrast-enhanced CT and bone scintigraphy were carried out up to 6 months before the 18F DOPA PET/CT. Results 77.7% were female and 27% had hereditary MTC. Median Ctn level was 1450 pg/ml [150-56620], median CEA level 413 ng/ml [2.9-7436]. Median Ctn DT was 37.5 months [5.7-240]; median CEA DT was 31.8 [4.9-180]. 18F-DOPA PET/CT was positive in 33 patients (91.6%); in 18 (56%) uptake was observed in lymph nodes in the neck or mediastinum, in 7 cases (22%) distant metastases were diagnosed, and in 8 additional patients (24%) both locoregional and distant sites of disease were found. Ctn and CEA levels were higher in patients with ≥ 3 foci of distant metastases. In 14 patients (38.8%), findings on 18F-DOPA PET/CT led to changes in management; surgery for locoregional lymph nodes was the most frequent procedure in 8 patients (22%). Conclusion 18F-DOPA PET/CT was useful for the detection of recurrent disease in MTC and provided helpful information for patient management.

A Baboon Brain Atlas for Magnetic Resonance Imaging and Positron Emission Tomography Image Analysis

The olive baboon (Papio anubis) is phylogenetically proximal to humans. Investigation into the baboon brain has shed light on the function and organization of the human brain, as well as on the mechanistic insights of neurological disorders such as Alzheimer’s and Parkinson’s. Non-invasive brain imaging, including positron emission tomography (PET) and magnetic resonance imaging (MRI), are the primary outcome measures frequently used in baboon studies. PET functional imaging has long been used to study cerebral metabolic processes, though it lacks clear and reliable anatomical information. In contrast, MRI provides a clear definition of soft tissue with high resolution and contrast to distinguish brain pathology and anatomy, but lacks specific markers of neuroreceptors and/or neurometabolites. There is a need to create a brain atlas that combines the anatomical and functional/neurochemical data independently available from MRI and PET. For this purpose, a three-dimensional atlas of the olive baboon brain was developed to enable multimodal imaging analysis. The atlas was created on a population-representative template encompassing 89 baboon brains. The atlas defines 24 brain regions, including the thalamus, cerebral cortex, putamen, corpus callosum, and insula. The atlas was evaluated with four MRI images and 20 PET images employing the radiotracers for [11C]benzamide, [11C]metergoline, [18F]FAHA, and [11C]rolipram, with and without structural aids like [18F]flurodeoxyglycose images. The atlas-based analysis pipeline includes automated segmentation, registration, quantification of region volume, the volume of distribution, and standardized uptake value. Results showed that, in comparison to PET analysis utilizing the “gold standard” manual quantification by neuroscientists, the performance of the atlas-based analysis was at >80 and >70% agreement for MRI and PET, respectively. The atlas can serve as a foundation for further refinement, and incorporation into a high-throughput workflow of baboon PET and MRI data. The new atlas is freely available on the Figshare online repository (https://doi.org/10.6084/m9.figshare.16663339), and the template images are available from neuroImaging tools & resources collaboratory (NITRC) (https://www.nitrc.org/projects/haiko89/).

Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study

Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p < 0.001) and DC (19.4% vs. 5.8%, p < 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months, p = 0.02). Arthralgia (OR 4.90, p = 0.0012), DO of PET/CT (OR 4.09, p = 0.016), CRP > 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis.

Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography

Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

Whole Body Muscle Activity During Weightlifting Exercise Evaluated By Positron Emission Tomography

Background: This study investigated the whole-body skeletal muscle activity pattern of hang power clean (HPC), a major weight training exercise, using positron emission tomography (PET). Methods: Twelve college weightlifting athletes performed three sets of HPC 20 times with a barbell set to 40 kg both before and after an intravenous injection of 37 MBq 18F-fluorodeoxyglucose (FDG). PET-computed tomography images were obtained 50 min after FDG injection. Regions of interest were defined within 71 muscles. The standardized uptake value was calculated to examine the FDG uptake of muscle tissue per unit volume, and FDG accumulation was compared to the control group. The Mann–Whitney U-test was used to evaluate the differences in the mean SUV between groups. The difference between SUVs of the right and left muscles was evaluated by a paired t-test. A P-value <0.05 was considered statistically significant.Results: FDG accumulation within the vastus lateralis, vastus intermedius, and vastus medialis was higher than that of the rectus femoris. FDG accumulation within the triceps surae muscle was significantly higher only in the soleus. In the trunk and hip muscles, FDG accumulation of only the erector spinae was significantly increased. In all skeletal muscles, there was no difference between SUVs of the right and left muscles.Conclusions: The monoarticular muscles in the lower limbs were active in HPC. In contrast, deep muscles in the trunk and hip were not active during HPC. HPC is not suitable for core training and needs to be supplemented with other training.

Considerations on Integrating Prostate-Specific Membrane Antigen Positron Emission Tomography Imaging Into Clinical Prostate Cancer Trials by National Clinical Trials Network Cooperative Groups

PURPOSE As prostate-specific membrane antigen (PSMA) positron emission tomography (PET) becomes increasingly available in the United States, the greater sensitivity of the technology in comparison to conventional imaging poses challenges for clinical trials. The NCI Clinical Imaging Steering Committee (CISC) PSMA PET Working Group was convened to coordinate the identification of these challenges in various clinical scenarios and to develop consensus recommendations on how best to integrate PSMA PET into ongoing and upcoming National Clinical Trials Network (NCTN) trials. METHODS NCI CISC and NCI Genitourinary Steering Committee members and leadership nominated clinicians, biostatisticians, patient advocates, and other imaging experts for inclusion in the PSMA PET Working Group. From April to July 2021, the working group met independently and in conjunction with the CISC to frame challenges, including stage migration, response assessment, trial logistics, and statistical challenges, and to discuss proposed solutions. An anonymous, open-ended survey was distributed to members to collect feedback on challenges faced. Representatives from each NCTN group were invited to present an overview of affected trials. From these discussions, the consensus document was developed and circulated for the inclusion of multiple rounds of feedback from both the Working Group and CISC. RESULTS The current consensus document outlines the key challenges for clinical prostate cancer trials resulting from the increasing availability of PSMA PET. We discuss implications for patient selection and definition of end points and provide guidance and potential solutions for different clinical scenarios, particularly with regard to best practices in defining eligibility criteria and outcome measures. RECOMMENDATIONS This article provides guidance regarding clinical trial design and conduct, and the interpretation of trial results.

Using inverse Laplace transform in positronium lifetime imaging

Positronium (Ps) lifetime imaging is gaining attention to bring out additional biomedical information from positron emission tomography (PET). The lifetime of Ps in vivo can change depending on the physical and chemical environments related to some diseases. Due to the limited sensitivity, Ps lifetime imaging may require merging some voxels for statistical accuracy. This paper presents a method for separating the lifetime components in the voxel to avoid information loss due to averaging. The mathematics for this separation is the inverse Laplace transform (ILT), and the authors examined an iterative numerical ILT algorithm using Tikhonov regularization, namely CONTIN, to discriminate a small lifetime difference due to oxygen saturation. The separability makes it possible to merge voxels without missing critical information on whether they contain abnormally long or short lifetime components. The authors conclude that ILT can compensate for the weaknesses of Ps lifetime imaging and extract the maximum amount of information.