Xin Cheng

Purpose Clinical studies of PET imaging using SSTR2 agonists have demonstrated high accuracy and correlation with SSTR2 expression in meningiomas. However, the usefulness of the SSTR2 antagonist with [⁶⁸ Ga]Ga-DOTA-JR11 is uncertain. To evaluate the diagnostic performance of [⁶⁸ Ga]Ga-DOTA-JR11 PET/CT and to clarify tumor characteristics in patients with suspected meningiomas. Materials and methods Patients with suspected de novo or recurrent meningioma in complex locations or atypical images were enrolled from August 2021 to October 2022 in prospective study. All patients underwent contrast-enhanced MRI (CE-MRI), [⁶⁸ Ga]Ga-DOTA-JR11 PET/CT, and histopathological evaluation. Tumor uptake of [⁶⁸ Ga]Ga-DOTA-JR11 was measured by SUVmax and tumor-endocranium ratio (TBR). Diagnostic performance was compared between PET and MRI. Results Of 36 (50.0 ± 13.0 years of age, 20 women) patients, 32 were histopathologically confirmed meningiomas and four with other tumors. [⁶⁸ Ga]Ga-DOTA-JR11 uptake was significantly higher in meningioma patients than in those with other tumors (SUVmax: 13.6 ± 7.7 vs. 5.2 ± 3.0, P < 0.001; TBR: 64.2 ± 27.7 vs. 25.0 ± 18.9, P = 0.001). [⁶⁸ Ga]Ga-DOTA-JR11 PET/CT detected 31 meningiomas, while CE-MRI detected 17 meningiomas of 25 initial diagnosis and 11 recurrent tumors; [⁶⁸ Ga]Ga-DOTA-JR11 PET had an incremental diagnostic value of 24% (6/25) over MRI in the group of initial diagnosis. There was no statistically significant difference in diagnostic efficacy between PET and MRI (P = 0.45) for all 36 patients. In skull base meningiomas, PET provided a more definitive diagnosis of pituitary involvement (in 12, not in12), compared to MRI (in eight, possible in six, possible not in six, not in four). PET revealed bone involvement in all 14 patients proven by pathology, while MRI identified only 11. Conclusions [⁶⁸ Ga]Ga-DOTA-JR11 PET/CT provided high image quality and presented an ideal diagnostic performance in detecting meningioma and evaluating the involvement of the pituitary and bone. The study provides valuable evidence for the use of [⁶⁸ Ga]Ga-DOTA-JR11 PET/CT as a complementary imaging modality to CE-MRI in the evaluation of meningiomas.

¹⁸F-choline (CHO) PET image remains noisy despite minimum physiological activity in the normal brain, and this study developed a deep learning-based denoising algorithm for brain tumor CHO PET. Thirty-nine presurgical CHO PET/CT data were retrospectively collected for patients with pathological confirmed primary diffuse glioma. Two conventional denoising methods, namely, block-matching and 3D filtering (BM3D) and non-local means (NLM), and two deep learning-based approaches, namely, Noise2Noise (N2N) and Noise2Void (N2V), were established for imaging denoising, and the methods were developed without paired data. All algorithms improved the image quality to a certain extent, with the N2N demonstrating the best contrast-to-noise ratio (CNR) (4.05 ± 3.45), CNR improvement ratio (13.60% ± 2.05%) and the lowest entropy (1.68 ± 0.17), compared with other approaches. Little changes were identified in traditional tumor PET features including maximum standard uptake value (SUVmax), SUVmean and total lesion activity (TLA), while the tumor-to-normal (T/N ratio) increased thanks to smaller noise. These results suggested that the N2N algorithm can acquire sufficient denoising performance while preserving the original features of tumors, and may be generalized for abundant brain tumor PET images.

Background: Ectopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS. The present study aimed to evaluate the usefulness of ¹⁸F-FDG PET/CT for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.Methods: We retrospectively reviewed the imaging data of 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent ¹⁸F-FDG PET/CT between 2008 and 2019. Eleven patients with lung tumors and 4 with pulmonary infections also had additional somatostatin receptor imaging (^99mTc-HYNIC-TOC SPECT/CT or ⁶⁸Ga-DOTATATE PET/CT).Results: In total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUV_max) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis revealed that a cut-off SUV_max of 4.95 helped in differentiating ACTH-secreting lung tumors from infections with 75% sensitivity and 94.4% specificity. For the 11 patients with ACTH-lung tumors, somatostatin receptor imaging (SRI) was positive in 6; while for the 4 with pulmonary infections, SRI was positive in 2. The sensitivity and specificity of somatostatin receptor imaging (SRI) for detecting ACTH-secreting lung tumor was 54.5% and 50%.Conclusions: Our findings suggest that pulmonary infections exhibit significantly higher FDG uptake than ACTH-secreting lung tumors in ¹⁸F-FDG PET/CT. An SUV_max cut-off value of 4.95 may be useful for differentiating the two conditions. Our results also suggested that SRI may not be an effective tool for differentiating the two conditions given the relatively low specificity.

Currently, glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. Fibroblast activation protein (FAP) is a member of the dipeptidyl peptidase family, which has catalytic activity and is engaged in protein recruitment and scaffolds. Recent studies have found that FAP expression in different types of cells within the GBM microenvironment is typically upregulated compared with that in lower grade glioma and is most pronounced in the mesenchymal subtype of GBM. As a marker of cancer-associated fibroblasts (CAFs) with tumorigenic activity, FAP has been proven to promote tumor growth and invasion via hydrolysis of molecules such as brevican in the extracellular matrix and targeting of downstream pathways and substrates, such as fibroblast growth factor 21 (FGF21). In addition, based on its ability to suppress antitumor immunity in GBM and induce temozolomide resistance, FAP may be a potential target for immunotherapy and reversing temozolomide resistance; however, current studies on therapies targeting FAP are still limited. In this review, we summarized recent progress in FAP expression profiling and the understanding of the biological function of FAP in GBM and raised the possibility of FAP as an imaging biomarker and therapeutic target.

Background: Ectopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS and occasionally difficult to differentiate from tumors by using computed tomography (CT) alone. The present study aimed to evaluate the usefulness of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT (¹⁸F-FDG PET/CT) for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.Methods: We retrospectively reviewed the imaging data for 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent ¹⁸F-FDG PET/CT between 2008 and 2019. Part of the 24 patients underwent ^99mTc-HYNIC-TOC scintigraphy and ⁶⁸Ga-DOTA-TATE PET/CT.Results: In total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUV_max) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis was performed, and it was found that a cut-off SUV_max of 4.95 helped in differentiating lung tumors from infections with 75% sensitivity and 94.4% specificity. In a subgroup analysis of 12 typical and five atypical carcinoids, there was no significant between-group difference with respect to SUV_max, the lesion size, the ACTH level, and the prevalence of regional lymph node metastasis. Four out of 6 patients with 5 infectious lesions and 16 out of 18 patients with 16 ACTH-secreting tumors underwent ^99mTc-HYNIC-TOC scintigraphy, and 1/6 patients with 1 infectious lesion, and 6 out of 18 patients with 6 ACTH-secreting tumors underwent ⁶⁸Ga-DOTA-TATE PET/CT. There is no significant difference in sensitivity between tumor lesions and infections using ^99mTc-HYNIC-TOC scintigraphy. Conclusions: Our findings suggest that pulmonary infections exhibit significantly higher FDG uptake than do well-differentiated ACTH-secreting lung tumors in ¹⁸F-FDG PET/CT. Therefore, SUV_max (cut-off 4.95) may be useful for differentiating the two conditions. However, ^99mTc-HYNIC-TOC scintigraphy is of no value in distinguishing the focus of well-differentiated ACTH-secreting lung tumors from that of infection. Typical and atypical ACTH-secreting lung carcinoids may show similar clinical behavior and appearance on ¹⁸F-FDG PET/CT.

Objective Isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation status are diagnostic, prognostic, predictive and therapeutic biomarkers for primary diffuse gliomas, and this study aimed to explore the relationship between choline (CHO) positron emission tomography (PET) parameters and these molecular alterations. Methods Twenty-eight patients who were histopathologically diagnosed with primary diffuse glioma and underwent presurgical CHO PET/CT were retrospectively analyzed, and IDH, TERT and MGMT alterations were examined. The volume of interest (VOI) was semiautomatically defined based on standardized uptake value (SUV) thresholds, and 5 traditional CHO parameters, namely, SUVmax, SUVmean, metabolic tumor volume (MTV), total lesion CHO uptake (TLC) and tumor-to-normal contralateral cortex activity ratio (T/N ratio), were calculated. Wilcoxon rank-sum tests and receiver operating characteristic (ROC) curves were applied to evaluate the differences and performances of the CHO parameters, and their capability to stratify patient prognosis was also evaluated. Results All 5 parameters were significantly higher in IDH-wildtype gliomas than in IDH-mutant gliomas (p = 0.0001–0.037), and SUVmax, SUVmean, TLC and the T/N ratio exhibited good performances in distinguishing the IDH status (areas under the ROC curve (AUCs) 0.856–0.918, accuracies 0.857–0.893) as well as stratifying patient prognosis. Although the differences and performances of the traditional parameters in distinguishing diverse TERT and MGMT statuses were moderate in the whole population, the T/N ratio and TLC displayed certain predictive value in discriminating the TERT status in the IDH-mutant and IDH-wildtype subgroups (p = 0.028–0.048, AUCs 0.857–0.860, accuracies 0.800–0.917, respectively). Conclusions Traditional CHO PET parameters are capable of distinguishing IDH but not TERT or MGMT alterations in the whole population. In accordance with the clinical understanding of TERT promoter mutations, the T/N ratio and TLC can also discriminate the TERT status in IDH subgroups.

Purpose: The aim of this study was to investigate the quantitative ¹⁸F-fluoroethylcholine (CHO) PET characteristics for differentiating lower-grade glioma (LGG) from glioblastoma (GBM). Patients and Methods: Thirty-nine patients who underwent CHO PET with histopathologically confirmed primary diffuse glioma were prospectively enrolled. The 3-dimensional region of interest was semiautomatically defined based on the SUV threshold, and a total of 74 quantitative features, including 13 shape features, 31 SUV-based features, and 30 normalized SUV-based features, were calculated. Wilcoxon rank sum test, receiver operating characteristic curve, and correlation coefficient analyses were applied to select independent representative features, and patient prognosis was stratified by the World Health Organization (WHO) grade and CHO features. Results: A total of 89.2% of the quantitative features were significantly different between LGG and GBM, and the SUV-based features displayed higher area under the receiver operating characteristic curve (AUC) values than the other feature groups. Among the 5 traditional features, the SUV_max and the total lesion CHO uptake were the most distinguishing, with AUCs of 0.880 and 0.860 (0.938 and 0.927 after reclassification of 2 outliers), respectively, both of which could also stratify patient prognosis better than WHO grade. Five alternative features, including 2 shape features and 3 SUV-based features, were considered representative, with AUCs ranging from 0.754 to 0.854. Conclusions: Quantitative features from CHO PET are reliable in determining the WHO grade of primary diffuse gliomas. Our findings suggest that GBM has a larger volume, a more spherical shape, higher choline activity in most interval segments, and a more symmetrical distribution than LGG.

Background: Autoimmune hypophysitis is a rare disease characterized by the infiltration of lymphocytic cells into the pituitary gland. ¹⁸F-fluorodeoxyglucose (FDG) and ¹⁸F-2-fluorodeoxy sorbitol (FDS) positron emission tomography (PET) are well-established and emerging techniques, respectively, which may aid in the diagnosis and classification of autoimmune hypophysitis. Case presentation: Here, we report a 40-year-old female diagnosed with central diabetes insipidus and multiple pituitary hormone deficiencies, and MRI revealed homogeneous signals in the pituitary gland as well as thickened in the pituitary stalk. FDG PET localized the pituitary and pituitary stalk lesions and displayed an SUVmax of 5.5. FDS, a sensitive radiotracer for bacterial infections but remains unproven under aseptic inflammation, also demonstrated elevated radioactivity, with an SUVmax of 1.1 at 30 min and 0.73 at 120 min. Transnasal biopsy suggested a diagnosis of autoimmune hypophysitis, and the patient displayed radiological and clinical improvement after treatment with glucocorticoids and hormone replacement. Conclusions: Autoimmune hypophysitis can display elevated FDG uptake, which aids in the localization of the lesions. In addition to revealing bacterial infection specifically, FDS can also accumulate under autoimmune conditions, suggesting that it could serve as a potential radiotracer for both bacterial and aseptic inflammation. Trial registration: The patient was enrolled in study NCT02450942 (clinicaltrials.gov, Registered May 21, 2015).