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.

STMO-5 Utilization of intraoperative multimodal technologies [PET and 5-ALA] for treating glioblastoma

Background: We can improve prognosis of glioblastoma by using positron emission tomography (PET) scans to guide them in removing tumors, and intraoperative magnetic resonance imaging (IoMRI) and 5-aminolevulinic acid (5-ALA) for identifying residual tumors. Tau proteins are reported to accumulate in glioblastomas, so we compared the efficacy of their PET tracer, THK5351, against that of 11C-MET, 18F-FLT, and 18F-FMISO. Methods: Patients (n = 11) underwent scans between February 2020 and July 2021 for glioblastoma resection. Tumor-to-normal tissue accumulation ratio (TNR) and accumulation volumes of 4 PET tracers were evaluated. Following excisions, 5-ALA fluorescent evaluation was classified as strong, vague, or none. Residual tumor volumes and removal rates were determined using T1Gd assessments and PET tracers. IoMRI confirmed presence of residual tumors.Results: THK5351 had a TNR of 5.20, and its accumulated volume was greater than that of other tracers: 1.80 for 11C-MET, 1.72 for 18F-FLT, and 2.82 for 18F-FMISO. 5-ALA fluorescent evaluation was vague (n = 7) or none (n = 4); respective residual tumor volumes (mL) were 2.3 and 0.2 (T1Gd), 5.7 and 0.9 (11C-MET), 5.6 and 0.6 (18F-FLT), 1.3 and 0.4 (18F-FMISO), and 7 and 1.4 (THK5351); respective tumor removal rates (%) were 90.4 and 99.6 (T1Gd), 79.2 and 86.4 (11C-MET), 84.4 and 89.2 (18F-FLT), 94.3 and 94.4 (18F-FMISO), and 72.3 and 83.4 (THK5351). The excised tumor tissue was found in the area where only THK5351 was accumulated.Conclusions: THK5351 accumulated in glioblastomas to a greater degree than that of other tracers, making it useful for discriminating between healthy and malignant tissues.

Tau Biomarkers in Dementia: Positron Emission Tomography Radiopharmaceuticals in Tauopathy Assessment and Future Perspective

Abnormal accumulation of Tau protein is closely associated with neurodegeneration and cognitive impairment and it is a biomarker of neurodegeneration in the dementia field, especially in Alzheimer’s disease (AD); therefore, it is crucial to be able to assess the Tau deposits in vivo. Beyond the fluid biomarkers of tauopathy described in this review in relationship with the brain glucose metabolic patterns, this review aims to focus on tauopathy assessment by using Tau PET imaging. In recent years, several first-generation Tau PET tracers have been developed and applied in the dementia field. Common limitations of first-generation tracers include off-target binding and subcortical white-matter uptake; therefore, several institutions are working on developing second-generation Tau tracers. The increasing knowledge about the distribution of first- and second-generation Tau PET tracers in the brain may support physicians with Tau PET data interpretation, both in the research and in the clinical field, but an updated description of differences in distribution patterns among different Tau tracers, and in different clinical conditions, has not been reported yet. We provide an overview of first- and second-generation tracers used in ongoing clinical trials, also describing the differences and the properties of novel tracers, with a special focus on the distribution patterns of different Tau tracers. We also describe the distribution patterns of Tau tracers in AD, in atypical AD, and further neurodegenerative diseases in the dementia field.

A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16

Purpose To quantify the synaptic vesicle glycoprotein 2A (SV2A) changes in the whole central nervous system (CNS) under pathophysiological conditions, a high affinity SV2A PET radiotracer with improved in vivo stability is desirable to minimize the potential confounding effect of radiometabolites. The aim of this study was to develop such a PET tracer based on the molecular scaffold of UCB-A, and evaluate its pharmacokinetics, in vivo stability, specific binding, and nonspecific binding signals in nonhuman primate brains, in comparison with [11C]UCB-A, [11C]UCB-J, and [18F]SynVesT-1. Methods The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one) and its two enantiomers were synthesized and assayed for in vitro binding affinities to human SV2A. We synthesized the enantiopure [18F]SDM-16 using the corresponding enantiopure arylstannane precursor. Nonhuman primate brain PET scans were performed on FOCUS 220 scanners. Arterial blood was drawn for the measurement of plasma free fraction (fP), radiometabolite analysis, and construction of the plasma input function. Regional time-activity curves (TACs) were fitted with the one-tissue compartment (1TC) model to obtain the volume of distribution (VT). Nondisplaceable binding potential (BPND) was calculated using either the nondisplaceable volume of distribution (VND) or the centrum semiovale (CS) as the reference region. Results SDM-16 was synthesized in 3 steps with 44% overall yield and has the highest affinity (Ki = 0.9 nM) to human SV2A among all reported SV2A ligands. [18F]SDM-16 was prepared in about 20% decay-corrected radiochemical yield within 90 min, with greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in monkey brains and was metabolically more stable than the other SV2A PET tracers. The fP of [18F]SDM-16 was 69%, which was higher than those of [11C]UCB-J (46%), [18F]SynVesT-1 (43%), [18F]SynVesT-2 (41%), and [18F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test–retest variability (TRV) was 7 ± 3%, and averaged absolute TRV (aTRV) was 14 ± 7% for the analyzed brain regions. Conclusion We have successfully synthesized a novel SV2A PET tracer [18F]SDM-16, which has the highest SV2A binding affinity and metabolical stability among published SV2A PET tracers. The [18F]SDM-16 brain PET images showed superb contrast between gray matter and white matter. Moreover, [18F]SDM-16 showed high specific and reversible binding in the NHP brains, allowing for the reliable and sensitive quantification of SV2A, and has potential applications in the visualization and quantification of SV2A beyond the brain.