F-18 FDG PET/CT Imaging in Normal Variants, Pitfalls and Artifacts in the Abdomen and Pelvis

Since its introduction into clinical practice, multimodality imaging has revolutionized diagnostic imaging for both oncologic and non-oncologic pathologies. 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging which takes advantage of increased anaerobic glycolysis that occurs in tumor cells (Warburg effect) has gained significant clinical relevance in the management of most, if not all oncologic conditions. Because FDG is taken by both normal and abnormal tissues, PET/CT imaging may demonstrate several normal variants and imaging pitfalls. These may ultimately impact disease detection and diagnostic accuracy. Imaging specialists (nuclear medicine physicians and radiologists) must demonstrate a thorough understanding of normal and physiologic variants in the distribution of 18F-FDG; including potential imaging pitfalls and technical artifacts to minimize misinterpretation of images. The normal physiologic course of 18F-FDG results in a variable degree of uptake in the stomach, liver, spleen, small and large bowel. Urinary excretion results in renal, ureteric, and urinary bladder uptake. Technical artifacts can occur due to motion, truncation as well as the effects of contrast agents and metallic hardware. Using pictorial illustrations, this paper aims to describe the variants of physiologic 18F-FDG uptake that may mimic pathology as well as potential benign conditions that may result in misinterpretation of PET/CT images in common oncologic conditions of the abdomen and pelvis.

Amino Acid and Proliferation PET/CT for the Diagnosis of Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by infiltration of monoclonal plasma cells in the bone marrow (BM). The standard examination performed for the assessment of bone lesions has progressed from radiographic skeletal survey to the more advanced imaging modalities of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). The Durie–Salmon PLUS staging system (upgraded from the Durie–Salmon staging system) applies 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) PET/CT, and MRI findings to the staging of MM, and 18F-FDG PET/CT has been incorporated into the International Myeloma Working Group (IMWG) guidelines for the diagnosis and staging of MM. However, 18F-FDG PET/CT has significant limitations in the assessment of diffuse BM infiltration and in the differentiation of MM lesions from inflammatory or infectious lesions. The potential of several new PET tracers that exploit the underlying disease mechanism of MM has been evaluated in terms of improving the diagnosis. L-type amino acid transporter 1 (LAT1), a membrane protein that transports neutral amino acids, is associated with cell proliferation and has strong ability to represent the status of MM. This review evaluates the potential of amino acid and proliferation PET tracers for diagnosis and compares the characteristics and accuracy of non-FDG tracers in the management of patients with MM.

Case Report: Pleuropulmonary Blastoma in a 2.5-Year-Old Boy: 18F-FDG PET/CT Findings

Pleuropulmonary blastoma (PPB) is a rare invasive primary malignancy in the thoracic cavity that occurs mainly in infants and children. It is often misdiagnosed and not treated correctly and promptly due to the lack of specificity of clinical symptoms and conventional imaging presentations. We report a 2.5-year-old boy who underwent X-ray chest radiography, chest CT, and 18F-FDG PET/CT. PET/CT images demonstrated a sizeable cystic-solid mass with heterogeneous increased glucose metabolism in the left thoracic cavity. The diagnosis of PPB (type II) was finally confirmed by a CT-guided puncture biopsy of the active tumor tissue. This case highlights the critical role of 18F-FDG PET/CT in the diagnosis of PPB in children.

Optimization and Evaluation of Al18F Labeling Using a NOTA—or RESCA1-Conjugated AE105 Peptide Antagonist of uPAR

Fluorine-18 displays almost ideal decay properties for positron emission tomography (PET) and allows for large scale production. As such, simplified methods to radiolabel peptides with fluorine-18 are highly warranted. Chelation of aluminium fluoride-18 toward specific peptides represents one method to achieve this. With the current methods, chelation of aluminium fluoride-18 can be achieved using NOTA-conjugated peptides. However, the heating to 90–100◦C that is required for this chelation approach may be deleterious to the targeting moiety of the probe. Recently, a new chelator, RESCA1, was developed allowing Al18F chelation at room temperature. Here, we optimize the labeling procedure enabling high chelation efficacy of fluoride-18 at 22◦C, even at full batch labeling. The optimized procedure was tested by Al18F-labeling of RESCA1-AE105—a uPAR targeting peptide. NOTA-AE105 was also labeled with Al18F, and the two peptides were compared head-to-head. [18F]AlF-NOTA-AE105 and [18F]AlF-RESCA1-AE105 could be produced in equal radiochemical yields (RCY), radiochemical purities (RCP) and molar activities. Additionally, the two peptides showed comparable binding affinity to uPAR and uptake in cells expressing the uPAR, when evaluated in vitro. Overall, we found that the performances of [18F]AlF-NOTA-AE105 and [18F]AlF-RESCA1-AE105 were grossly comparable, but importantly RESCA1 can be labeled with aluminium fluoride-18 at 22◦C. Consequently, this study showed that RESCA1 is superior to NOTA with respect to Al18F chelation of temperature sensitive molecules, such as thermolabile peptides and proteins as well as that full batch chelation of RESCA1 with fluoride-18 is possible.

Clinical Outcomes After Radioiodine Therapy, According to the Method of Preparation by Recombinant TSH vs. Endogenous Hypothyroidism, in Thyroid Cancer Patients at Intermediate-High Risk of Recurrence

Background: To effectively treat differentiated thyroid carcinoma (DTC) with radioiodine therapy (RAI), it is necessary to raise serum thyrotropin levels, either by thyroid hormone withdrawal (THW) or by administration of recombinant human TSH (rhTSH). The use of rh-TSH is controversial in DTC patients at intermediate to high risk of recurrence. Even more controversial is the question of whether is alters progression-free survival rates and overall survival in more aggressive patients.Objective: The primary objective of this study was comparing clinical outcomes according to the method of preparation of RAI in intermediate to high DTC patients who presented progression of structural disease.Methods: This retrospective study included 81 patients with initial intermediate to high DTC and progression of structural disease at the end of follow-up. In 21 patients, all RAI treatments were done with only rhTSH stimulation. In 11, RAI treatments were done either with thyroid hormone withdrawal (THW) or rhTSH. In 49 patients, all RAI treatments were done only THW.Results: After a median follow-up time of 83 months, there were no statistical differences in the clinical outcomes (status of structural disease at the end of the follow-up, death rate, overall survival curve, and progression-free survival curve).Conclusions: Preparation for RAI therapy using either rhTSH stimulation or THW was associated with no inferiority in the clinical outcomes in progressive DTC patients at higher risk of recurrence.

Fully Automated 68Ga-Labeling and Purification of Macroaggregated Albumin Particles for Lung Perfusion PET Imaging

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [68Ga]Ga-MAA labeling procedure, using a commercially available [99mTc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [68Ga]Ga-MAA.Method: The synthesis parameters (pH, heating temperature) were manually determined. Automated 68Ga-labeling of MAA was then developed on a miniAIO (Trasis®, Ans, Belgium) module. An innovative automated process was developed for the purification. The process was then optimized and adapted to automate both the [68Ga]Ga-MAA synthesis and the isolation of gallium-68 eluate required for the pulmonary ventilation PET/CT.Results: The 15-min process demonstrated high reliability and reproducibility, with high synthesis yield (>95 %). Mean [68Ga]Ga-MAA radiochemical purity was 99 % ± 0.6 %. The 68Ga-labeled MAA particles size and morphology remained unchanged.Conclusion: A fast, user friendly, and fully automated process to produce GMP [68Ga]Ga-MAA for clinical use was developed. This automated process combining the advantages of using a non-modified MAA commercial kit, a gallium-68 eluate without pre-purification and an efficient final purification of the [68Ga]Ga-MAA may facilitate the implementation of lung PET/CT imaging in nuclear medicine departments.

Radiosynthesis of [11C]Ibrutinib via Pd-Mediated [11C]CO Carbonylation: Preliminary PET Imaging in Experimental Autoimmune Encephalomyelitis Mice

Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [11C]ibrutinib through 11C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [11C]CO, iodoethylene, and palladium–NiXantphos. [11C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; n = 9, relative to starting [11C]CO2), radiochemical purity >99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [11C]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.

Bone Scintigraphy of Vertebral Fractures With a Whole-Body CZT Camera in a PET-Like Utilization

Objective: An image display with a standardized uptake value (SUV) scale is recommended for analyzing PET exams, thus requiring the reconstruction of accurate images for both SUV measurement and visual analysis. This study aimed to determine whether such images may also be obtained with a high-speed CZT-SPECT/CT system, with a further application for the longitudinal monitoring of vertebral fractures.Materials and Methods: SPECT image reconstruction was optimized with an IEC phantom according to both image quality parameters and accuracy of measured activity. The optimized reconstruction process was applied to ≤15 min 99mTc-HDP SPECT spine recordings previously acquired from 25 patients (74 ± 12 years old) at both early (1.3 ± 1.1 months) and late (5.2 ± 2.3 months) stages after an acute vertebral fracture.Results: A SPECT reconstruction with 32 equivalent iterations was selected based on the association of high detectability for spheres down to 0.6 ml in volume, with accurate measured activity, although the latter was affected by partial volume effect for spheres ≤5.6 ml. Coherent measurements were obtained on these high-quality SPECT images for the SUVmax from the intact vertebrae of patients, which were stable between basal SPECT/CT and follow-up SPECT/CT (for T1 vertebrae: 5.7 ± 1.1 vs. 5.8 ± 1.1, p = 0.76), and from initially fractured vertebrae, which were dramatically higher on the basal compared with the follow-up SPECT (21.0 ± 8.5 vs. 11.2 ± 4.2, p < 0.001), whereas inverse changes in SUVmax were observed for newly compacted fractures identified on follow-up SPECT (74.4 ± 2.0 vs. 21.8 ± 10.3, p = 0.002). Finally, an image display with an SUV scale was shown to be advantageous for highlighting areas with >7.5 SUV, a level reached by 98% of vertebral fractures of <7 months and 4% of reference intact vertebrae.Conclusion: Bone scintigraphy of vertebral fractures may be obtained with this CZT-SPECT/CT system with fast 3D acquisitions and high-quality images displayed with a reliable SUV scale, approaching what is achieved and recommended for PET imaging.