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Background: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) has been suggested as a useful imaging method for diagnosing cyst infections in patients with autosomal dominant polycystic kidney disease (ADPKD). The aim of this article is to provide evidence-based data in this setting., Methods: A systematic literature review (exploring several bibliographic databases) and a bivariate meta-analysis were carried out to calculate the pooled diagnostic performance of [ 18 F]FDG PET/CT in diagnosing probable cyst infection in ADPKD., Results: Ten studies (282 PET/CT scans and 249 patients) were included in the analysis. The pooled sensitivity and specificity of [ 18 F]FDG PET/CT in this setting were 84.6% (95% confidence interval: 75.4-90.7) and 94.9% (95% confidence interval: 72.6-99.2), respectively, without statistical heterogeneity or significant publication bias. [ 18 F]FDG PET/CT significantly changed patient management in more than half of ADPKD patients with suspected cyst infection., Conclusions: [ 18 F]FDG PET/CT has high performance in diagnosing probable cyst infections in ADPKD patients with an impact on management in the majority of patients. Although more studies are warranted, the provided evidence-based data are an important step towards the integration of [ 18 F]FDG PET/CT in clinical and diagnostic guidelines on probable cyst infection in ADPKD patients.

Here, we describe the case of a 43-year-old male patient with a metastatic parathyroid carcinoma who underwent dual-tracer whole-body positron emission tomography/computed tomography (PET/CT) with [ 18 F]fluorocholine and fluorodeoxyglucose ([ 18 F]FDG) for staging. [ 18 F]FDG PET/CT detected multiple cervical and mediastinal lymph nodal lesions with increased tracer uptake, whereas [ 18 F]fluorocholine PET/CT detected increased tracer uptake on cervical and mediastinal lymph nodal lesions and bone and lung lesions with a better evaluation of metastatic spread. Due to these imaging findings, the patient underwent systemic treatment with chemotherapy. This case demonstrates the added value of dual-tracer PET/CT in this rare metastatic tumor.

Background: Recent studies have suggested using positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals for the detection of salivary gland malignancies (SGM), particularly adenoid-cystic carcinoma (ACC)., Methods: The authors conducted an extensive review of the scientific literature to examine the potential diagnostic role of PET/CT using PSMA-targeting radiopharmaceuticals in salivary gland malignancies (SGMs) and adenoid cystic carcinoma (ACC). This study included newly diagnosed SGM patients and those with disease recurrence in their imaging evaluation., Results: This updated systematic review included a total of six studies that examined the diagnostic performance of PSMA-targeted PET/CT in ACC. The articles provided evidence of a high detection rate of PSMA-targeting PET/CT in ACC across all clinical contexts examined. SGMs other than ACC exhibited poorer diagnostic performance., Conclusions: PSMA-targeted PET/CT seems promising in detecting ACC lesions; moreover, PSMA appears to be a suitable potential target for radioligand therapy. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting radiopharmaceuticals in ACC, as both diagnostic and theragnostic agents.

Background: Anemia is the main extraintestinal comorbidity of Inflammatory Bowel Disease (IBD). Differentiating the type of anemia in these disorders is still a challenge. Hepcidin could be a promising biomarker to identify iron deficiency anemia (IDA), anemia of chronic disease (ACD) and the concomitant presence of both IDA and ACD., Methods: To evaluate the potential role of hepcidin dosage in the management of anemia in IBD patients, we performed a systematic review by a comprehensive literature analysis of original papers reporting the dosage of hepcidin in IBD patients. In all the articles reviewed, the dosage of ferritin was reported, and the correlation between hepcidin and ferritin has been used to compare these two biomarkers., Results: A total of 12 articles concerning the dosage of hepcidin in IBD were included, comprising in total of 976 patients. The results of the hepcidin values in IBD patients when compared with controls were conflicting. In fact, four articles described an increase in this biomarker, three showed a decrease and five did not find significant differences. The correlation with ferritin was positive and significant. In three studies, some differences between hepcidin dosages and ferritin levels indicate a possible role when IDA and ACD could be present at the same time., Conclusions: Considering the contradictory data of the studies, the diagnostic role of hepcidin as a biomarker remains elusive in IBD patients. These differences could be due to the clinical characteristics of the patients enrolled that should be better defined in the future. A suitable clinical trial should be designed to outline the possible role of hepcidin in differentiating IDA, ACD and concomitant IDA and ACD in IBD patients. At the moment, ferritin still remains the best marker to diagnose these conditions, in addition to hemoglobin, transferrin saturation and CRP as recommended by the ECCO guidelines.

Background: 18 F-Fluciclovine ([ 18 F]FACBC) has been recently proposed as a synthetic radiolabeled amino acid for positron emission tomography (PET) imaging in patients with brain neoplasms. Our aim is to evaluate the diagnostic performance of [ 18 F]FACBC PET in high-grade glioma (HGG) patients, taking into account the literature data., Methods: A comprehensive literature search was performed. We included original articles evaluating [ 18 F]FACBC PET in the detection of HGG before therapy and for the suspicion of tumor recurrence. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratios (DOR), including 95% confidence intervals (95% CI), were measured. Statistical heterogeneity and publication bias were also assessed., Results: ten studies were included in the review and eight in the meta-analysis (113 patients). Regarding the identification of HGG, the sensitivity of [ 18 F]FACBC PET ranged between 85.7% and 100%, with a pooled estimate of 92.9% (95% CI: 84.4-96.9%), while the specificity ranged from 50% to 100%, with a pooled estimate of 70.7% (95% CI: 47.5-86.5%). The pooled LR+, LR-, and DOR of [ 18 F]FACBC PET were 2.5, 0.14, and 37, respectively. No significant statistical heterogeneity or publication bias were found., Conclusions: evidence-based data demonstrate the good diagnostic accuracy of [ 18 F]FACBC PET for HGG detection. Due to the still limited data, further studies are warranted to confirm the promising role of [ 18 F]FACBC PET in this context.

We describe the case of a 67-year-old male patient with a moderately differentiated hepatocellular carcinoma (HCC) of the right liver lobe who underwent [ 18 F]fluorocholine positron emission tomography/computed tomography (PET/CT) for staging due to a suspicious lung lesion at previous CT scan. [ 18 F]fluorocholine PET/CT showed increased radiopharmaceutical uptake in a liver lesion corresponding to the known HCC. Furthermore, a right pulmonary hilar lesion suspicious for metastatic spread of HCC showed increased radiopharmaceutical uptake. Surprisingly, the histological assessment of the thoracic lesion demonstrated the presence of small cell lung cancer (SCLC). The patient underwent treatment with radiation therapy and chemotherapy for the SCLC and selective internal radiation therapy (SIRT) for the HCC. The patient died after one year due to progressive SCLC. This case demonstrates that coexisting tumors showing increased cell membrane turnover, including SCLC, can be detected by [ 18 F]fluorocholine PET/CT. In our case, [ 18 F]fluorocholine PET/CT findings influenced the patient management in terms of histological verification and different treatment of the detected lesions.

Background: this study aims to explore the prognostic and predictive role of volumetric parameters on [ 68 Ga]Ga-DOTATOC PET/CT in neuroendocrine tumors (NET) patients treated with peptide receptor radionuclide therapy (PRRT)., Methods: We retrospectively evaluated 39 NET patients (21 male, 18 female; mean age 60.7 y) within the FENET-2016 trial (CTiD:NCT04790708). PRRT was proposed with [ 177 Lu]Lu-DOTATOC alone or combined with [ 90 Y]Y-DOTATOC. [ 68 Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after PRRT. For each PET/CT, we calculated SUVmax, SUVmean, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), as well as their percentage of changes (Δ), both for liver (_L) and for total tumor burden (_WB). Early clinical response (3 months after PRRT) and PFS were evaluated according to RECIST 1.1 and institutional NET board., Results: Early clinical response identified 9 partial response (PR), 25 stable disease (SD), and 5 progressive disease (PD). Post-SRETV_WB and ΔSRETV_WB were progressively increased among response groups ( p = 0.02 and p = 0.03, respectively). Likewise, median post-SRETV_L was significantly higher in PD patients ( p = 0.03). SUVmax and TLSRE did not correlate with early clinical response. Median PFS was 31 months. Patients with ΔSRETV_WB lower than -4.17% as well as those with post-SRETV_WB lower than 34.8 cm 3 showed a longer PFS ( p = 0.006 and p = 0.06, respectively). Finally, multivariate analysis identified ΔSRETV_WB as an independent predictor for PFS., Conclusions: our results could strengthen the importance of evaluating the burden of disease on [ 68 Ga]Ga-DOTATOC PET/CT in NET patients treated with PRRT.

Background: Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in radioiodine-refractory thyroid cancer (TC)., Methods: The authors accomplished a comprehensive literature search of original articles concerning the performance of PSMA-targeted PET/CT in TC patients. Original papers exploring this molecular imaging examination in radioiodine-refractory TC patients undergoing restaging of their disease were included., Results: A total of 6 documents concerning the diagnostic performance of PSMA-targeted PET/CT in TC (49 patients) were included in this systematic review. The included articles reported heterogeneous values of PSMA-targeted PET/CT detection rates in TC, ranging from 25% to 100% and overall inferior to [ 18 F]-fluorodeoxyglucose PET/CT when the two molecular imaging examinations were compared. Two studies reported the administration of [ 177 Lu]PSMA-radioligands with theragnostic purpose in three patients., Conclusions: The available literature data in this setting are limited and heterogeneous. The employment of PET with PSMA-targeting radiopharmaceuticals in this setting did not affect patient management. Nevertheless, prospective multicentric studies are needed to properly assess its potential role in TC patients.

Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis., Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I 2 test., Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3-99.9%), specificity 91.2% (95% CI: 68.4-98.1%), LR+ 4.5 (95% CI: 2.2-9.3), LR- 0.07 (95% CI: 0.04-0.15), and DOR 70.1 (95% CI: 19.6-250.9). No significant statistical heterogeneity among the included studies was found (I 2 = 0%)., Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

Patients with primary hyperparathyroidism (pHPT) can develop persistent (P-pHPT) or recurrent (R-pHPT) disease after parathyroidectomy. Before recommending reoperation, recurrence must be accurately identified because of the high risk of complications. Our study evaluates 18 F-fluorocholine ( 18 F-FCH) PET/CT and 4D-CT integrated in PET/4D-CT in patients with P-pHPT/R-pHPT. Patients with P-pHPT/R-pHPT investigated by 18 F-FCH PET/4D-CT between May 2018 and March 2021 were retrospectively included. Forty-two patients were included, 37 of whom underwent 4D-CT. The sensitivity and detection rate (DR%) were 95% and 88% for 18 F-FCH PET/CT and 70% and 63% for 4D-CT, respectively. PET/CT and 4D-CT were concordant in 18/24 glands and concordant and positive in 15/24 (63%) glands. Discordant results were obtained for 6/24 glands. The surgical success rate was 65%. PET/CT showed significantly higher sensitivity than 4D-CT. Dynamic CT allowed the identification of no additional glands missed by PET/CT, and the combination of the 2 techniques did not improve the sensitivity or DR%. 18 F-FCH PET/CT appears to be a valuable technique to accurately detect hyperfunctioning parathyroid tissue in patients with P-pHPT/R-pHPT and is better than 4D-CT. Except for cases with doubtful locations of PET targets that may require 4D-CT for surgical guidance, standard nonenhanced 18 F-FCH PET/CT can be effectively recommended in patients with P-pHPT/R-pHPT before reoperation.

We describe the case of a 45-year-old woman with an unusual presentation of metastatic ovarian cancer. The patient presented to the oncological clinic with a three-week history of skin rash on the right breast. She underwent a chest and abdomen CT scan, which showed skin thickening of the right breast, right pleural effusion and bilateral cystic ovarian masses. Biopsy of a left ovarian lesion by diagnostic laparoscopy revealed the presence of ovarian serous carcinoma. Biopsy of the breast skin lesion revealed the presence of carcinomatous lymphangitis and immunohistochemistry documented the ovarian origin.

We describe the case of a 74-year-old female patient previously treated with radiation therapy for a meningioma of the skull base and with surgery for a right tympanic paraganglioma. After the morphological progression of the meningioma demonstrated by magnetic resonance imaging (MRI), the patient underwent somatostatin receptor positron emission tomography/computed tomography (SR-PET/CT) with Gallium-68 DOTATATE for restaging. This examination showed increased somatostatin receptor expression by the meningioma and confirmed its extension as already assessed by MRI (endocranial extension, skull base involvement and invasion of the right orbit). Furthermore, SR-PET/CT detected two small right jugulotympanic pararagangliomas with high somatostatin receptor expression. Lastly, SR-PET/CT demonstrated that this patient would be an ideal candidate for peptide receptor radionuclide therapy (PRRT) that can be used for the treatment of progressive/treatment-refractory meningiomas and relapsed paragangliomas with high somatostatin receptors expression, both conditions coexisting in this case.

Background: The use of prostate-specific membrane antigen (PSMA)-targeted agents for staging prostate cancer (PCa) patients using positron emission tomography/computed tomography (PET/CT) is increasing worldwide. We performed a systematic review on the role of 18 F-PSMA-1007 PET/CT in PCa staging to provide evidence-based data in this setting., Methods: A comprehensive computer literature search of PubMed/MEDLINE and Cochrane Library databases for studies using 18 F-PSMA-1007 PET/CT in PCa staging was performed until 31 December 2020. Eligible articles were selected and relevant information was extracted from the original articles by two authors independently., Results: Eight articles (369 patients) evaluating the role of 18 F-PSMA-1007 PET/CT in PCa staging were selected. These studies were quite heterogeneous, but, overall, they demonstrated a good diagnostic accuracy of 18 F-PSMA-1007 PET/CT in detecting PCa lesions at staging. Overall, higher primary PCa aggressiveness was associated with higher 18 F-PSMA-1007 uptake. When compared with other radiological and scintigraphic imaging methods, 18 F-PSMA-1007 PET/CT had superior sensitivity in detecting metastatic disease and the highest inter-reader agreement. 18 F-PSMA-1007 PET/CT showed similar results in terms of diagnostic accuracy for PCa staging compared with PET/CT with other PSMA-targeted tracers. Dual imaging with multi-parametric magnetic resonance imaging and 18 F-PSMA-1007 PET/CT may improve staging of primary PCa. Notably, 18 F-PSMA-1007-PET/CT may detect metastatic disease in a significant number of patients with negative standard imaging., Conclusions: 18 F-PSMA-1007 PET/CT demonstrated a good accuracy in PCa staging, with similar results compared with other PSMA-targeted radiopharmaceuticals. This method could substitute bone scintigraphy and conventional abdominal imaging for PCa staging. Prospective multicentric studies are needed to confirm these findings.

Background: Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE)., Methods: Selected articles evaluating the diagnostic accuracy of 18 F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis., Results: Seven studies (351 episodes of suspected NVE) were included. 18 F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18 F-FDG PET/CT in a multimodality strategy., Conclusions: In our systematic review and meta-analysis, 18 F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

Background: Some studies evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) for the detection of post-transplant lymphoproliferative disorder (PTLD). As there is no clear consensus about the diagnostic accuracy of these imaging methods, we performed a meta-analysis on this topic., Methods: A comprehensive computer literature search of PubMed, Embase, and Cochrane library databases through December 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of 18 F-FDG PET or PET/CT for detection of PTLD were calculated., Results: Five studies reporting data on the diagnostic performance of 18 F-FDG PET or PET/CT in 336 transplant recipients were included in the systematic review and bivariate meta-analysis. Pooled sensitivity and specificity for detection of PTLD were 89.7% (95% confidence interval (95%CI): 84.6-93.2%) and 90.9% (95%CI: 85.9-94.3%), respectively. Pooled LR+, LR-, and DOR were 8.9 (95%CI: 5.7-14), 0.13 (95%CI: 0.08-0.2), and 70.4 (95%CI: 35.4-140), respectively. A significant heterogeneity among studies was not detected., Conclusions: Despite limited literature data, 18 F-FDG PET or PET/CT demonstrated good diagnostic performance for the detection of PTLD, but large prospective studies are needed to strengthen these findings., Competing Interests: The authors declare no conflicts of interest.

Background: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR., Methods: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model., Results: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2-95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis., Conclusions: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication., Competing Interests: The authors declare no conflicts of interest.

Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose ( 18 F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic., Methods: A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of 18 F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated., Results: Eight studies on the use of 18 F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75-92.9%], specificity 92% (95%CI 79.8-97.1%), LR+ 6.6 (95%CI: 3.1-14.1), LR- 0.2 (95%CI: 0.12-0.33), DOR 43.5 (95%CI: 12.2-155). A statistically significant heterogeneity was not detected., Conclusions: Despite limited literature data, 18 F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed.