Over the past decade, several strategies have revolutionized the clinical management of patients with cutaneous melanoma (CM), including immunotherapy and targeted tyrosine kinase inhibitor (TKI)-based therapies. Indeed, immune checkpoint inhibitors (ICIs), alone or in combination, represent the standard of care for patients with advanced disease without an actionable mutation. Notably BRAF combined with MEK inhibitors represent the therapeutic standard for disease disclosing BRAF mutation. At the same time, FDG PET/CT has become part of the routine staging and evaluation of patients with cutaneous melanoma. There is growing interest in using FDG PET/CT measurements to predict response to ICI therapy and/or target therapy. While semiquantitative values such as standardized uptake value (SUV) are limited for predicting outcome, new measures including tumor metabolic volume, total lesion glycolysis and radiomics seem promising as potential imaging biomarkers for nuclear medicine. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on radiomics approaches that could improve outcomes in CM.

BACKGROUND: Brain positron emission tomography/computed tomography (PET/CT) scans are useful for identifying the cause of dementia by evaluating glucose metabolism in the brain with F-18-fluorodeoxyglucose or Aβ deposition with F-18-florbetaben. However, since imaging time ranges from 10 to 30 minutes, movements during the examination might result in image artifacts, which interfere with diagnosis. To solve this problem, data-driven brain motion correction (DDBMC) techniques are capable of performing motion corrected reconstruction using highly accurate motion estimates with high temporal resolution. In this study, we investigated the effectiveness of DDBMC techniques on PET/CT images using a Hoffman phantom, involving continuous rotational and tilting motion, each expanded up to approximately 20 degrees.
METHODS: Listmode imaging was performed using a Hoffman phantom that reproduced rotational and tilting motions of the head. Brain motion correction processing was performed on the obtained data. Reconstructed images with and without brain motion correction processing were compared. Visual evaluations by a nuclear medicine specialist and quantitative parameters of images with correction and reference still images were compared.
RESULTS: Normalized Mean Squared Error (NMSE) results demonstrated the effectiveness of DDBMC in compensating for rotational and tilting motions during PET imaging. In Cases 1 and 2 involving rotational motion, NMSE decreased from 0.15-0.2 to approximately 0.01 with DDBMC, indicating a substantial reduction in differences from the reference image across various brain regions. In the Structural Similarity Index (SSIM), DDBMC improved it to above 0.96 Contrast assessment revealed notable improvements with DDBMC. In continuous rotational motion, % contrast increased from 42.4% to 73.5%, In tilting motion, % contrast increased from 52.3% to 64.5%, eliminating significant differences from the static reference image. These findings underscore the efficacy of DDBMC in enhancing image contrast and minimizing motion induced variations across different motion scenarios.
CONCLUSIONS: DDBMC processing can effectively compensate for continuous rotational and tilting motion of the head during PET, with motion angles of approximately 20 degrees. However, a significant limitation of this study is the exclusive validation of the proposed method using a Hoffman phantom; its applicability to the human brain has not been investigated. Further research involving human subjects is necessary to assess the generalizability and reliability of the presented motion correction technique in real clinical scenarios.

UNASSIGNED: We report a rare case of intramedullary spinal cord malakoplakia mimicking malignancy on 18F-FDG PET/CT. A 61-year-old man underwent a contrast-enhanced spinal cord MRI to evaluate 1 week of progressive left-sided weakness. Spinal cord MRI showed a 1.3-cm enhancing intramedullary cervical spinal cord mass at C5 level with cord edema. Subsequently, 18F-FDG PET/CT was performed for evaluation. The images showed a well-circumscribed hypermetabolic mass in the spinal cord; no lesions were suggestive of malignancy or metastasis. A subtotal tumor excision was performed; histopathological examination revealed malakoplakia. This emphasizes the significance of histopathological evaluation and the importance of diagnostic confirmation.

UNASSIGNED: FDG PET/CT is a well-documented imaging investigation to evaluate fever of unknown origin (FUO). Brucellosis is one of the causes of FUO, which can be missed as it requires a longer incubation period for growth on culture media. Rarely, it can involve the prostate. Here, we present a case of FUO with initial negative blood and urine cultures and no localizing signs or symptoms. 18F-FDG PET/CT revealed hypermetabolism in the prostate and seminal vesicles. A repeat blood and urine culture showed the growth of Brucella species after 5 days of incubation, and the patient responded to Brucella-directed antibiotic therapy.

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [18F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [18F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [18F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [18F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.

OBJECTIVE: To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group.
METHODS: Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS).
RESULTS: In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected).
CONCLUSIONS: 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

BACKGROUND: Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in patients with head and neck squamous cell carcinoma (HNSCC).
OBJECTIVE: The aim of the study was to investigate the prognostic value of pre- and post-treatment maximum standardized uptake values (SUVmax) in 18F-FDG PET/CT imaging for predicting mortality in patients with HNSCC, as well as its prognostic value in terms of disease progression, overall survival (OS), and progression-free survival (PFS).
METHODS: This retrospective study included 37 patients with a histopathological diagnosis of HNSCCs between 2015 and 2018. In patients with HNSCC, the first 18F-FDG PET/CT imaging was performed for pre-treatment staging, and the second imaging was performed to evaluate post-treatment response. In these imaging studies, SUVmax values of the primary tumor before and after treatment were determined. After the second imaging, patients were re-evaluated and followed up. ROC analysis was used to determine the predictive value of 18F-FDG PET/CT SUVmax parameters in terms of death and progression, and Cox regression analysis was used to investigate the prognostic value in terms of OS and PFS.
RESULTS: Cut-off value 15 for SUVmax1 (pre-treatment) had a significant predictive value for mortality (P = 0.02). Cut-off value 3.1 for SUVmax2 (post-treatment) had a significant predictive value for progression (P = 0.024). In univariate analysis, both SUVmax1 and SUVmax2 values were significant prognostic factors for OS (P = 0.047, P = 0.004). However, for PFS, only the SUVmax2 value was a significant prognostic factor (P = 0.001).
CONCLUSIONS: SUVmax1 value of the primary tumor at diagnosis in HNSCC patients has a predictive value for mortality and a prognostic value for OS. However, the SUVmax2 value in the primary tumor after treatment is a predictive factor for progression and a prognostic factor for both OS and PFS.

OBJECTIVE: To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC).
METHODS: Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage.
RESULTS: A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on 18F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17).
CONCLUSIONS: The proposed risk score based on preoperative CA 19-9, CT, and 18F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.