UNASSIGNED: Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications.
UNASSIGNED: A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed.
UNASSIGNED: Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).

Concurrently acquired positron emission tomography and computed tomography (PET-CT) is an advanced imaging modality with diverse oncologic applications, including staging, therapeutic assessment, restaging and longitudinal surveillance. This series of six review articles focuses on providing practical information to providers and imaging professionals regarding the best use and interpretative strategies of PET-CT for oncologic indications in adult patients. In this fourth article of the series, the more common gynecological and adult genitourinary malignancies encountered in clinical practice are addressed, with an emphasis on Food and Drug Administration (FDA)-approved and clinically available radiopharmaceuticals. The advent of new FDA-approved radiopharmaceuticals for prostate cancer imaging has revolutionized PET-CT imaging in this important disease, and these are addressed in this report. However, [18F]F-fluoro-2-deoxy-d-glucose (FDG) remains the mainstay for PET-CT imaging of gynecologic and many other genitourinary malignancies. This information will serve as a guide for the appropriate role of PET-CT in the clinical management of gynecologic and genitourinary cancer patients for health care professionals caring for adult cancer patients. It also addresses the nuances and provides guidance in the accurate interpretation of FDG PET-CT in gynecological and genitourinary malignancies for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

Clinical assessment of frontotemporal lobar degeneration (FTLD)/primary progressive aphasia (PPA) patients is challenging, given that common cognitive assessments rely extensively on language. Since asymmetry in neuroimaging biomarkers is often described as a central finding in these patients, our study evaluated [18F]-fluorodeoxyglucose (FDG) uptake patterns in patients meeting clinical and imaging criteria for FTLD, with emphasis on PPA. Fifty-one subjects underwent brain [18F]-FDG positron-emission tomography/magnetic resonance imaging (PET/MRI) as part of their routine clinical workup for dementia and neurodegenerative disease. Images were obtained using a Siemens Biograph mMR integrated 3T PET/MRI scanner. PET surface maps and fusion fluid-attenuated inversion recovery-PET images were generated utilizing MIMneuro software. Two board-certified neuroradiologists and one nuclear medicine physician blinded to patient history classified each FTLD/PPA subtype and assessed for left- versus right-side dominant hypometabolism. Qualitative and semiquantitative assessment demonstrated 18 cases of PPA, 16 behavioral variant frontotemporal dementia (bvFTD), 12 corticobasal degeneration, and 5 progressive supranuclear palsy. Among the 18 PPA subjects (11 svPPA, 5 lvPPA, and 2 agPPA), 12 (67%) demonstrated left-dominant hypometabolism and 6 (33%) right-dominant hypometabolism. While existing literature stresses left-dominant hypometabolism as a key imaging feature in the PPA subtypes, a third of our cases demonstrated right-dominant hypometabolism, suggesting that emphasis should be placed on the functionality of specific brain regions affected, rather than left versus right sidedness of hypometabolism patterns.

This study aimed to explore the clinical utility of [68Ga]Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) relative to [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT and magnetic resonance imaging (MRI) for primary staging and recurrence detection in nasopharyngeal carcinoma (NPC).
This retrospective analysis utilized a sub-cohort of patients from a previously acquired database. Patients with NPC who underwent [18F]FDG and [68Ga]Ga-FAPI PET/CT between October 2019 and November 2020 were included. The radiotracer uptake and clinical staging/restaging performances of [18F]FDG and [68Ga]Ga-FAPI PET/CT were compared.
Forty-five participants (39 for initial assessment, 6 for recurrence detection) were included. In treatment-naïve participants, [68Ga]Ga-FAPI PET/CT showed higher radiotracer uptake than [18F]FDG PET/CT in primary tumors (16.18 vs. 10.11, P < 0.001), regional lymph nodes (11.42 vs. 7.37, P < 0.001), and bone and visceral metastases (6.94 vs. 3.11, P < 0.001). Compared with the [18F]FDG-based TNM stage, the [68Ga]Ga-FAPI-based TNM stage was upgraded in ten patients (26%), resulting in management changes in seven patients (18%). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated the T stage in four and two patients, respectively. In post-treatment patients, [68Ga]Ga-FAPI PET/CT yielded more true-positive findings than [18F]FDG PET/CT in detecting local recurrence.
[68Ga]Ga-FAPI PET/CT is a promising imaging modality for the diagnosis of primary and metastatic NPC. The exact tumor geographic imaging obtained through [68Ga]Ga-FAPI PET/CT may be a supplement to MRI for T staging and radiotherapy planning.

BACKGROUND: We recently reported that enhanced [18F]-fluorodeoxyglucose (FDG) uptake in skeletal muscles predicts disease aggressiveness in patients with amyotrophic lateral sclerosis (ALS). The present experimental study aimed to assess whether this predictive potential reflects the link between FDG uptake and redox stress that has been previously reported in different tissues and disease models.
METHODS: The study included 15 SOD1G93A mice (as experimental ALS model) and 15 wildtype mice (around 120 days old). Mice were submitted to micro-PET imaging. Enzymatic pathways and response to oxidative stress were evaluated in harvested quadriceps and hearts by biochemical, immunohistochemical, and immunofluorescence analysis. Colocalization between the endoplasmic reticulum (ER) and the fluorescent FDG analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) was performed in fresh skeletal muscle sections. Finally, mitochondrial ultrastructure and bioenergetics were evaluated in harvested quadriceps and hearts.
RESULTS: FDG retention was significantly higher in hindlimb skeletal muscles of symptomatic SOD1G93A mice with respect to control ones. This difference was not explained by any acceleration in glucose degradation through glycolysis or cytosolic pentose phosphate pathway (PPP). Similarly, it was independent of inflammatory infiltration. Rather, the high FDG retention in SOD1G93A skeletal muscle was associated with an accelerated generation of reactive oxygen species. This redox stress selectively involved the ER and the local PPP triggered by hexose-6P-dehydrogenase. ER involvement was confirmed by the colocalization of the 2-NBDG with a vital ER tracker. The oxidative damage in transgenic skeletal muscle was associated with a severe impairment in the crosstalk between ER and mitochondria combined with alterations in mitochondrial ultrastructure and fusion/fission balance. The expected respiratory damage was confirmed by a deceleration in ATP synthesis and oxygen consumption rate. These same abnormalities were represented to a markedly lower degree in the myocardium, as a sample of non-voluntary striated muscle.
CONCLUSIONS: Skeletal muscle of SOD1G93A mice reproduces the increased FDG uptake observed in ALS patients. This finding reflects the selective activation of the ER-PPP in response to significant redox stress associated with alterations of mitochondrial ultrastructure, networking, and connection with the ER itself. This scenario is less severe in cardiomyocytes suggesting a relevant role for either communication with synaptic plaque or contraction dynamics.

OBJECTIVE: To compare [18F]-fluorodeoxyglucose (FDG) and [18F]-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) with whole-body magnetic resonance with diffusion-weighted imaging (WB-MRI), for endocrine therapy response prediction at 8 weeks in bone-predominant metastatic breast cancer.
METHODS: Thirty-one patients scheduled for endocrine therapy had up to five bone metastases measured [FDG, NaF PET/CT: maximum standardized uptake value (SUVmax); WB-MRI: median apparent diffusion coefficient (ADCmed)] at baseline and 8 weeks. To detect the flare phenomenon, a 12-week NaF PET/CT was also performed if 8-week SUVmax increased. A 25% parameter change differentiated imaging progressive disease (PD) from non-PD and was compared to a 24-week clinical reference standard and progression-free survival (PFS).
RESULTS: Twenty-two patients (median age, 58.6 years, range, 40-79 years) completing baseline and 8-week imaging were included in the final analysis. Per-patient % change in NaF SUVmax predicted 24-week clinical PD with sensitivity, specificity and accuracy of 60, 73.3, and 70%, respectively. For FDG SUVmax the results were 0, 100, and 76.2% and for ADCmed, 0, 100 and 72.2%, respectively. PFS < 24 weeks was associated with % change in SUVmax (NaF: 41.7 vs. 0.7%, p = 0.039; FDG: - 4.8 vs. - 28.6%, p = 0.005) but not ADCmed (- 0.5 vs. 10.1%, p = 0.098). Interlesional response heterogeneity occurred in all modalities and NaF flare occurred in seven patients.
CONCLUSIONS: FDG PET/CT and WB-MRI best predicted clinical non-PD and both FDG and NaF PET/CT predicted PFS < 24 weeks. Lesional response heterogeneity occurs with all modalities and flare is common with NaF PET/CT.

In Alzheimer\'s disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement.
To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults.
Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention.
Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization.
Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.

BACKGROUND: (11)C-methonine ([(11)C]-MET) positron emission tomography-computed tomography (PET-CT) is a well-established technique for evaluation of tumor for diagnosis and treatment planning in neurooncology. [(11)C]-MET reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging (MRI) in stereotactic biopsy planning. This study compared fluorodeoxyglucose (FDG) PET-CT and MET PET-CT in the detection of various brain tumors.
METHODS: Sixty-four subjects of brain tumor treated by surgery, chemotherapy, and/or radiotherapy were subjected to [(18)F]-FDG, [(11)C]-MET, and MRI scan. The lesion was analyzed semiquantitatively using tumor to normal contralateral ratio. The diagnosis was confirmed by surgery, stereotactic biopsy, clinical follow-up, MRI, or CT scans.
RESULTS: Tumor recurrence was found in 5 out of 22 patients on [F-18] FDG scan while [(11)C]-MET was able to detect recurrence in 18 out of 22 patients in low-grade gliomas. Two of these patients were false positive for the presence of recurrence of tumor and later found to be harboring necrosis. Among oligodendroglioma, medulloblastoma and high-grade glioma out of 42 patients 39 were found to be concordant MET and FDG scans. On semiquantitative analysis, mean T/NT ratio was found to be 2.96 ± 0.94 for lesions positive for recurrence of tumors and 1.18 ± 0.74 for lesions negative for recurrence of tumor on [(11)C]-MET scan. While the ratio for FDG scan on semiquantitative analysis was found to be 2.05 ± 1.04 for lesions positive for recurrence of tumors and 0.52 ± 0.15 for lesions negative for recurrence of tumors.
CONCLUSIONS: The study highlight that [(11)C]-MET is superior to [(18)F]-FDG PET scans to detect recurrence in low-grade glioma. A cut-off value of target to nontarget value of 1.47 is a useful parameter to distinguish benign from malignant lesion on an [(11)C]-MET Scan. Both [(18)F]-FDG and [(11)C]-MET scans were found to be useful in high-grade astrocytoma, oligodendroglioma, and medulloblastoma.

OBJECTIVE: Many studies have shown that a position task is more difficult than a force task although both are performed at a similar net muscle force. Thus, the time to task failure is consistently shown to be briefer during the position task. The contributions of the central nervous system to these two types of fatiguing contractions are not completely understood. The purpose of this pilot study was to examine differences in regional brain activity between force and position tasks using positron emission tomography (PET) with [(18)F]-Fluorodeoxyglucose (FDG).
METHODS: Two participants performed both a force and position task, separated by 7 days, with the elbow flexor muscles at 15% maximal voluntary contraction force. During both tasks, each participant was injected with ≈ 256 (SD 11) MBq of FDG. Immediately after both tasks PET imaging was performed and images were analyzed to determine FDG uptake within regions of the brain.
RESULTS: FDG uptake was greater in the occipital and temporal cortices of the brain during the position task compared to the force task.
CONCLUSIONS: These findings suggest that differences in visual-spatial feedback and processing may play a role in the reduced time to failure of position tasks. Future application of these findings may lead to improved designs of rehabilitative strategies involving different types of visual feedback.

Clinical molecular imaging by use of PET and PET/CT is increasingly important in routine oncological practice worldwide. A vast majority of clinical PET investigations are performed with [(18)F]-fluorodeoxyglucose (FDG), but there is a growing interest in novel molecular probes among scientists and clinicians. Beyond FDG, a small number of different tracers have been shown to be of clinical value. With a growing commercial interest in tracer development, many more are under investigation. This review provides some examples of clinical situations where tracers other than FDG have been found useful and an outlook towards technical and regulatory development needed to allow the full impact of clinical PET to benefit the individual patient.