Combination of pre-treatment dynamic [18F]FET PET radiomics and conventional clinical parameters for the survival stratification in patients with IDH-wildtype glioblastoma.

PURPOSE: The aim of this study was to build and evaluate a prediction model which incorporates clinical parameters and radiomic features extracted from static as well as dynamic [18F]FET PET for the survival stratification in patients with newly diagnosed IDH-wildtype glioblastoma. METHODS: A total of 141 patients with newly diagnosed IDH-wildtype glioblastoma and dynamic [18F]FET PET prior to surgical intervention were included. Patients with a survival time ≤ 12 months were classified as short-term survivors. First order, shape, and texture radiomic features were extracted from pre-treatment static (tumor-to-background ratio; TBR) and dynamic (time-to-peak; TTP) images, respectively, and randomly divided into a training (n = 99) and a testing cohort (n = 42). After feature normalization, recursive feature elimination was applied for feature selection using 5-fold cross-validation on the training cohort, and a machine learning model was constructed to compare radiomic models and combined clinical-radiomic models with selected radiomic features and clinical parameters. The area under the ROC curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive values were calculated to assess the predictive performance for identifying short-term survivors in both the training and testing cohort. RESULTS: A combined clinical-radiomic model comprising six clinical parameters and six selected dynamic radiomic features achieved highest predictability of short-term survival with an AUC of 0.74 (95% confidence interval, 0.60-0.88) in the independent testing cohort. CONCLUSIONS: This study successfully built and evaluated prediction models using [18F]FET PET-based radiomic features and clinical parameters for the individualized assessment of short-term survival in patients with a newly diagnosed IDH-wildtype glioblastoma. The combination of both clinical parameters and dynamic [18F]FET PET-based radiomic features reached highest accuracy in identifying patients at risk. Although the achieved accuracy level remained moderate, our data shows that the integration of dynamic [18F]FET PET radiomic data into clinical prediction models may improve patient stratification beyond established prognostic markers.

Biodistribution and dosimetry for combined [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy using multi-isotope quantitative SPECT imaging.

PURPOSE: Quantitative SPECT for patient-specific dosimetry is a valuable tool in the scope of radionuclide therapy, although its clinical application for 225Ac-based treatments may be limited due to low therapeutic activities. Therefore, the aim of this study was to demonstrate the feasibility of clinical quantitative low-count SPECT imaging during [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T treatment. METHODS: Eight prostate cancer patients (1000 MBq/8 MBq [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T) received a single-bed quantitative 177Lu/225Ac SPECT/CT acquisition (1 h) at 24 h post treatment (high-energy collimator, 16 projections p. head à 3.5 min, 128 × 128 pixel). The gamma peak at 440 keV (width: 10%) of the progeny 213Bi was imaged along with the peak at 208 keV (width: 15%) of 177Lu. Quantification included CT-based attenuation and window-based scatter correction plus resolution modelling. Gaussian post-filtering with a full-width-half-maximum of 30 mm and 40-45 mm was employed to match the signal-to-noise ratio of 225Ac and 177Lu, respectively. RESULTS: Kidney (r = 0.96, p < 0.01) and lesion (r = 0.94, p < 0.01) SUV for [177Lu]Lu-PSMA-I&T and [225Ac]Ac-PSMA-I&T showed a strong and significant correlation. Kidney SUV were significantly higher (p < 0.01) for [225Ac]Ac-PSMA-I&T (2.5 ± 0.8 vs. 2.1 ± 0.9), while for [177Lu]Lu-PSMA-I&T lesion SUV were significantly higher (p = 0.03; 1.8 ± 1.1 vs. 2.1 ± 1.5). For absorbed dose estimates, significant differences regarding the kidneys remained, while no significant differences for lesion dosimetry were found. CONCLUSION: Quantitative low-count SPECT imaging of the peak at 440 keV during [225Ac]Ac-PSMA-I&T therapy is feasible. Multi-isotope imaging for [177Lu]Lu-PSMA-I&T/[225Ac]Ac-PSMA-I&T therapy indicates accumulation of free 213Bi in the kidneys.

Feasibility of [68Ga]Ga-FAPI-46 PET/CT for detection of nodal and hematogenous spread in high-grade urothelial carcinoma.

BACKGROUND: [68Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [18F]FDG in UC, [68Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [68Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors. METHODS: Fifteen patients with UC prior to or after local treatment underwent [68Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUVmean and SUVmax). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT). RESULTS: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUVmax 20.8 (range, 8.1-27.8)) followed by lymph node metastases (SUVmax 10.6 (range, 4.7-29.1)). In 4/15 (26.7%) patients there were [68Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy. CONCLUSION: [68Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [68Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients.

Prediction of TERTp-mutation status in IDH-wildtype high-grade gliomas using pre-treatment dynamic [18F]FET PET radiomics.

PURPOSE: To evaluate radiomic features extracted from standard static images (20-40 min p.i.), early summation images (5-15 min p.i.), and dynamic [18F]FET PET images for the prediction of TERTp-mutation status in patients with IDH-wildtype high-grade glioma. METHODS: A total of 159 patients (median age 60.2 years, range 19-82 years) with newly diagnosed IDH-wildtype diffuse astrocytic glioma (WHO grade III or IV) and dynamic [18F]FET PET prior to surgical intervention were enrolled and divided into a training (n = 112) and a testing cohort (n = 47) randomly. First-order, shape, and texture radiomic features were extracted from standard static (20-40 min summation images; TBR20-40), early static (5-15 min summation images; TBR5-15), and dynamic (time-to-peak; TTP) images, respectively. Recursive feature elimination was used for feature selection by 10-fold cross-validation in the training cohort after normalization, and logistic regression models were generated using the radiomic features extracted from each image to differentiate TERTp-mutation status. The areas under the ROC curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive value were calculated to illustrate diagnostic power in both the training and testing cohort. RESULTS: The TTP model comprised nine selected features and achieved highest predictability of TERTp-mutation with an AUC of 0.82 (95% confidence interval 0.71-0.92) and sensitivity of 92.1% in the independent testing cohort. Weak predictive capability was obtained in the TBR5-15 model, with an AUC of 0.61 (95% CI 0.42-0.80) in the testing cohort, while no predictive power was observed in the TBR20-40 model. CONCLUSIONS: Radiomics based on TTP images extracted from dynamic [18F]FET PET can predict the TERTp-mutation status of IDH-wildtype diffuse astrocytic high-grade gliomas with high accuracy preoperatively.

Clinical impact of follicular oncocytic (Hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma.

PURPOSE: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). METHODS: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. RESULTS: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). CONCLUSIONS: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Dosimetry and optimal scan time of [18F]SiTATE-PET/CT in patients with neuroendocrine tumours.

PURPOSE: Radiolabelled somatostatin analogues targeting somatostatin receptors (SSR) are well established for combined positron emission tomography/computer tomography (PET/CT) imaging of neuroendocrine tumours (NET). [18F]SiTATE has recently been introduced showing high image quality, promising clinical performance and improved logistics compared to the clinical reference standard 68Ga-DOTA-TOC. Here we present the first dosimetry and optimal scan time analysis. METHODS: Eight NET patients received a [18F]SiTATE-PET/CT (250 ± 66 MBq) with repeated emission scans (10, 30, 60, 120, 180 min after injection). Biodistribution in normal organs and SSR-positive tumour uptake were assessed. Dosimetry estimates for risk organs were determined using a combined linear-monoexponential model, and by applying 18F S-values and reference target masses for the ICRP89 adult male or female (OLINDA 2.0). Tumour-to-background ratios were compared quantitatively and visually between different scan times. RESULTS: After 1 h, normal organs showed similar tracer uptake with only negligible changes until 3 h post-injection. In contrast, tracer uptake by tumours increased progressively for almost all types of metastases, thus increasing tumour-to-background ratios over time. Dosimetry resulted in a total effective dose of 0.015 ± 0.004 mSv/MBq. Visual evaluation revealed no clinically relevant discrepancies between later scan times, but image quality was rated highest in 60 and 120 min images. CONCLUSION: [18F]SiTATE-PET/CT in NET shows overall high tumour-to-background ratios from 60 to 180 min after injection and an effective dose comparable to 68Ga-labelled alternatives. For clinical use of [18F]SiTATE, the best compromise between image quality and tumour-to-background contrast is reached at 120 min, followed by 60 min after injection.

The diagnostic challenge of coexistent sarcoidosis and thyroid cancer - a retrospective study.

BACKGROUND: Sarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes. METHODS: We screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8-15.0 years)). RESULTS: Median age at first diagnosis of TC was 50.1 years (33.0-71.5 years) and of sarcoidosis 39.4 years (18.0-63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion. CONCLUSION: Physicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.

Clinical value of [18F]FDG-PET/CT and 3D-black-blood 3T-MRI for the diagnosis of large vessel vasculitis and single-organ vasculitis of the aorta.

BACKGROUND: We aimed to investigate the clinical value of a 3D-T1w turbo-spin-echo (TSE) sequence and [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) for the diagnosis of active large vessel vasculitis (LVV) and single-organ vasculitis (SOV) of the aorta. METHODS: Twenty-four patients with suspected vasculitis who underwent MRI and PET/CT were retrospectively evaluated. MRI was analyzed for concentric contrast enhancement and wall thickening, and flow artifact intensity (4-point-scales). PET/CT analysis comprised qualitative, quantitative and semiquantitative methods. Imaging findings were correlated with final diagnosis derived from the clinical follow-up data. RESULTS: Fifteen of 24 patients had a clinically confirmed active vasculitis, two had inactive vasculitis and 7 no vasculitis. [18F]FDG-PET/CT and 3D-T1w TSE-MRI revealed both a high diagnostic accuracy of 88% and 83%, respectively. In patients in whom both PET/CT and MRI showed concordant findings (19 patients), the accuracy increased to 95% with a high positive predictive value (92%) and negative predictive value (100%); thus, a correct diagnosis was obtained in 18 of 19 patients. Among the five patients with discordant findings PET/CT correctly identified the two patients without active vasculitis while rated false positive on MRI. Of the three remaining patients with active vasculitis, two were correctly identified by MRI and one by PET/CT. CONCLUSIONS: 3D-T1w TSE-MRI and [18F]FDG-PET/CT are both useful in the diagnosis of active vasculitis with high diagnostic accuracies. The diagnostic accuracy was even optimized by combining the two analysis methods. Therefore, there might be substantial potential for the application of whole-body hybrid PET/MRI in the evaluation of vasculitis in future studies.

Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic 18F-FET PET.

PURPOSE: According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. 18F-FET PET has been shown to be an important diagnostic tool for glioma management. The aim of this study was to assess the value of dynamic 18F-FET PET for the non-invasive prediction of the IDH-mutation status. METHODS: Newly diagnosed WHO grade II-IV glioma patients with MRI and dynamic 18F-FET PET were included. The 18F-FET PET parameters mean and maximal tumour-to-background ratio (TBRmean, TBRmax) and minimal time-to-peak (TTPmin) were evaluated. The diagnostic power for the prediction of the IDH genotype (positive/negative predictive value) was tested in the overall study group and in the subgroup of non-contrast enhancing gliomas. RESULTS: Three hundred forty-one patients were evaluated. Molecular analyses revealed 178 IDH-mutant and 163 IDH-wildtype tumours. Overall, 270/341 gliomas were classified as 18F-FET-positive (TBRmax > 1.6), 90.2% of the IDH-wildtype and 69.1% of IDH-mutant gliomas. Median TBRmax was significantly higher in IDH-wildtype compared with IDH-mutant gliomas (2.9 vs. 2.3, p < 0.001); however, ROC-analyses revealed no reliable cutoff due to a high overlap (range 1.0-7.1 vs. 1.1-7.9). Dynamic analysis revealed a significantly shorter TTPmin in IDH-wildtype gliomas; using TTPmin ≤ 12.5 min as indicator for IDH-wildtype gliomas, a positive predictive value of 87% was reached (negative predictive value 72%, AUC = 0.796, p ≤ 0.001). A total of 161/341 gliomas did not show contrast enhancement on MRI; even within this subgroup, TTPmin ≤ 12.5 min remained a good predictor of IDH-wildtype glioma (positive predictive value 83%, negative predictive value 90%; AUC = 0.868, p < 0.001). CONCLUSION: A short TTPmin in dynamic 18F-FET PET serves as good predictor of highly aggressive IDH-wildtype status in gliomas. In particular, a high diagnostic power was observed in the subgroup of non-contrast enhancing gliomas, which helps to identify patients with worse prognosis.

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

PURPOSE: Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11 % of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. METHODS: A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. RESULTS: OPTC patients were significantly older (55.2 ± 12.3 years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8 cm for OPTC patients, 1.5 ± 1.2 cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. CONCLUSION: At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

[18F]FDG PET accurately differentiates infected and non-infected non-unions after fracture fixation.

PURPOSE: Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [18F]FDG PET in suspected infections of non-union fractures. METHODS: We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [18F]FDG PET/CT (N = 24), [18F]FDG PET (N = 11) plus additional CT (N = 8), or conventional X-ray (N = 3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up. RESULTS: In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N = 12) or positive follow-up (N = 1). [18F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUVmax was 6.4 ± 2.7 in the clinically infected group and 3.0 ± 1.7 in the clinically non-infected group (p <0.01). The SUVratio was 5.3 ± 3.3 in the clinically infected group and 2.6 ± 1.5 in the clinically non-infected group (p <0.01). CONCLUSION: [18F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [18F]FDG PET should be considered for therapeutic management of non-unions.

The added value of 68Ga-DOTA-TATE-PET to contrast-enhanced CT for primary site detection in CUP of neuroendocrine origin.

OBJECTIVES: To quantify the additional value of 68Ga-DOTA-TATE PET/CT in comparison with contrast-enhanced CT alone for primary tumour detection in neuroendocrine cancer of unknown primary (CUP-NET). METHODS: In total, 38 consecutive patients (27 men, 11 women; mean age 62 years) with histologically proven CUP-NET who underwent a contrast-enhanced 68Ga-DOTA-TATE PET/CT scan for primary tumour detection and staging between 2010 and 2014 were included in this IRB-approved retrospective study. Two blinded readers independently analysed the contrast-enhanced CT and 68Ga-DOTA-TATE PET datasets separately and noted from which modality they suspected a primary tumour. Consensus was reached if the results were divergent. Postoperative histopathology (24 patients) and follow-up 68Ga-DOTA-TATE PET/CT imaging (14 patients) served as the reference standards and statistical measures of diagnostic accuracy were calculated accordingly. RESULTS: The majority of confirmed primary tumours were located in the abdomen (ileum in 19 patients, pancreas in 12, lung in 2, small pelvis in 1). High interobserver agreement was noted regarding the suspected primary tumour site (Cohen's k 0.90, p < 0.001). 68Ga-DOTA-TATE PET demonstrated a significantly higher sensitivity (94 % vs. 63 %, p = 0.005) and a significantly higher accuracy (87 % vs. 68 %, p = 0.003) than contrast-enhanced CT. CONCLUSIONS: Ga-DOTA-TATE PET/CT compared with contrast-enhanced CT alone provides an improvement in sensitivity of 50 % and an improvement in accuracy of 30 % in primary tumour detection in CUP-NET. KEY POINTS: • 68Ga-DOTA-TATE PET augments the sensitivity of contrast-enhanced CT by 50 % • 68Ga-DOTA-TATE PET augments the accuracy of contrast-enhanced CT by 30 % • Somatostatin receptor-targeted hybrid imaging optimizes primary tumour detection in CUP-NET.

The diagnostic value of [(18)F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection.

PURPOSE: The diagnosis of osteomyelitis and implant-associated infections in patients with nonspecific laboratory or radiological findings is often unsatisfactory. We retrospectively evaluated the contributions of [(18)F]FDG PET and [(18)F]FDG PET/CT to the diagnosis of osteomyelitis and implant-associated infections, enabling timely and appropriate decision-making for further therapy options. METHODS: [(18)F]FDG PET or PET/CT was performed in 215 patients with suspected osteomyelitis or implant-associated infections between 2000 and 2013. We assessed the diagnostic accuracy of both modalities together and separately with reference to intraoperative microbial findings, with a mean clinical follow-up of 69 ± 49 months. RESULTS: Infections were diagnosed clinically in 101 of the 215 patients. PET and PET/CT scans revealed 87 true-positive, 76 true-negative, 38 false-positive, and 14 false-negative results, indicating a sensitivity of 86 %, a specificity of 67 %, a positive predictive value (PPV) of 70 %, a negative predictive value (NPV) of 84 % and an accuracy of 76 %. The sensitivity of PET/CT was 88 %, but specificity, PPV, NPV and accuracy (76 %, 76 %, 89 % and 82 %, respectively) were higher than those of stand-alone PET. CONCLUSION: [(18)F]FDG PET is able to identify with high sensitivity the presence of osteomyelitis in orthopaedic surgery patients with nonspecific clinical symptoms of infection.

Early static (18)F-FET-PET scans have a higher accuracy for glioma grading than the standard 20-40 min scans.

PURPOSE: Current guidelines for glioma imaging by positron emission tomography (PET) using the amino acid analogue O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) recommend image acquisition from 20-40 min post injection (p.i.). The maximal tumour-to-background evaluation (TBRmax) obtained in these summation images does not enable reliable differentiation between low and high grade glioma (LGG and HGG), which, however, can be achieved by dynamic (18)F-FET-PET. We investigated the accuracy of tumour grading using TBRmax values at different earlier time points after tracer injection. METHODS: Three hundred and fourteen patients with histologically proven primary diagnosis of glioma (131 LGG, 183 HGG) who had undergone 40-min dynamic (18)F-FET-PET scans were retrospectively evaluated. TBRmax was assessed in the standard 20-40 min summation images, as well as in summation images from 0-10 min, 5-15 min, 5-20 min, and 15-30 min p.i., and kinetic analysis was performed. TBRmax values and kinetic analysis were correlated with histological classification. ROC analyses were performed for each time frame and sensitivity, specificity, and accuracy were assessed. RESULTS: TBRmax values in the earlier summation images were significantly better for tumour grading (P < 0.001) when compared to standard 20-40 min scans, with best results for the early 5-15 min scan. This was due to higher TBRmax in the HGG (3.9 vs. 3.3; p < 0.001), while TBRmax remained nearly stable in the LGG (2.2 vs. 2.1). Overall, accuracy increased from 70 % in the 20-40 min analysis to 77 % in the 5-15 min images, but did not reach the accuracy of dynamic analysis (80 %). CONCLUSIONS: Early TBRmax assessment (5-15 min p.i.) is more accurate for the differentiation between LGG and HGG than the standard static scan (20-40 min p.i.) mainly caused by the characteristic high (18)F-FET uptake of HGG in the initial phase. Therefore, when dynamic (18)F-FET-PET cannot be performed, early TBRmax assessment can be considered as an alternative for tumour grading.

Suspected pulmonary embolism in patients with pulmonary fibrosis: Discordance between ventilation/perfusion SPECT and CT pulmonary angiography.

BACKGROUND AND OBJECTIVE: Pulmonary embolism (PE) is a common differential diagnosis in patients with pulmonary fibrosis presenting with a clinical deterioration. Both ventilation/perfusion (V/Q)-single photon emission computed tomography (SPECT) and computed tomographic pulmonary angiography (CTPA) are routinely used to detect PE. However, the value of V/Q-SPECT and CTPA in this scenario has not been studied so far. We aimed to investigate the concordance of V/Q-SPECT and CTPA in patients with pulmonary fibrosis and suspicion of pulmonary embolism. METHODS: A total of 22 consecutive patients with pulmonary fibrosis and clinical deterioration who underwent both V/Q-SPECT and CTPA were included in the study and analyzed for the presence of pulmonary embolism. RESULTS: Nine of 22 patients (41%) had evidence for pulmonary embolism in V/Q-SPECT, and two of these patients had matching evidence for pulmonary embolism in CTPA. In the other seven patients with positive findings in V/Q-SPECT, no evidence of pulmonary embolism was found in CTPA. None of the 13 patients with a negative V/Q-SPECT had evidence for pulmonary embolism in CTPA. CONCLUSION: In patients with pulmonary fibrosis and suspected pulmonary embolism, pulmonary embolism is detected more frequently by V/Q-SPECT than by CTPA. Thromboembolic disease is identified on CTPA only in a minority of patients with positive findings on V/Q-SPECT. When making treatment decisions, clinicians should be aware of the high rate of discordant findings in V/Q-SPECT and CTPA in this specific patient population.

Synchronous neuroendocine liver metastases in comparison to primary pancreatic neuroendocrine tumors on MRI and SSR-PET/CT.

Background: The study aimed to compare and correlate morphological and functional parameters in pancreatic neuroendocrine tumors (pNET) and their synchronous liver metastases (NELM), while also assessing prognostic imaging parameters. Methods: Patients with G1/G2 pNET and synchronous NELM underwent pretherapeutic abdominal MRI with DWI and 68Ga-DOTATATE/TOC PET/CT were included. ADC (mean, min), SNR_art and SNT_T2 (SNR on arterial phase and on T2) and SUV (max, mean) for three target NELM and pNET, as well as tumor-free liver and spleen (only in PET/CT) were measured. Morphological parameters including size, location, arterial enhancement, cystic components, T2-hyperintensity, ductal dilatation, pancreatic atrophy, and vessel involvement were noted. Response evaluation used progression-free survival (PFS) with responders (R;PFS>24 months) and non-responders (NR;PFS ≤ 24 months). Results: 33 patients with 33 pNETs and 95 target NELM were included. There were no significant differences in ADC and SUV values between NELM and pNET. 70% of NELM were categorized as hyperenhancing lesions, whereas the pNETs exhibited significantly lower rate (51%) of hyperenhancement (p<0.01) and significant lower SNR_art. NELM were qualitatively and quantitatively (SNR_T2) significantly more hyperintense on T2 compared to pNET (p=0.01 and p<0.001). NELM of R displayed significantly lower ADCmean value in comparison to the ADC mean value of pNET (0.898 versus 1.037x10-3mm²/s,p=0.036). In NR, T2-hyperintensity was notably higher in NELM compared to pNET (p=0.017). The hepatic tumor burden was significantly lower in the R compared to the NR (10% versus 30%). Conclusions: Arterial hyperenhancement and T2-hyperintensity differ between synchronous NELM and pNET. These findings emphasize the importance of a multifaceted approach to imaging and treatment planning in patients with these tumors as well as in predicting treatment responses.

Evaluation of MRI in the diagnostic accuracy of extrahepatic metastases in neuroendocrine tumors in comparison with the reference standard somatostatin-receptor-PET/CT.

Purpose: The aim of this study was to compare the diagnostic performance of different sets of MR sequences in detecting extrahepatic disease of NETs on routine liver magnetic resonance imaging (MRI). Method: One hundred twenty-seven patients with NETs with and without hepatic and extrahepatic metastases who underwent liver MRI and SSTR-PET/CT were retrospectively analyzed. Two radiologists evaluated in consensus in four sessions: (1) non-contrast T1w+T2w (NC), (2) NC+DWI, (3) NC+ contrast-enhanced T1w (CE), and (4) NC+DWI+CE the presence and number of metastases (lymph nodes, bone, peritoneal surface, lung base, and abdominal organ). Sensitivity, specificity, positive, and negative predictive value for detection of metastases were calculated for each session in a patient-based manner; detection and error rates were calculated for lesion-based analysis. Comparison between the MR-sessions and positron emission tomography-computed tomography (PET/CT) was performed with the McNemar test. Results: Regarding all 1,094 lesions detected in PET/CT, NC+DWI, and NC, CE+DWI identified most true-positive lesions 779 (71%) and 775 (71%), respectively. Patient-based analysis revealed significantly higher sensitivity by NC+DWI (85%) than NC and NC+CE (p = 0.011 and 0.004, respectively); the highest specificity was reached by NC+CE+DWI (100%). Site-based analysis revealed highest detection rates for lymph node metastases for NC+DWI and NC, CE+DWI (73 and 76%, respectively); error rates were lower for NC, CE+DWI with 5% compared with 17% (NC+DWI). Detection rates for bone metastases were similarly high in NC+DWI and NC, CE+DWI (75 and 74%, respectively), while CE showed no benefit. For peritoneal metastases highest sensitivity was reached by NC+DWI (67%). Conclusion: The combination of NC+DWI showed better sensitivities than the combination of NC+CE. NC+DWI showed similar, sometimes even better sensitivities than NC+CE+DWI, but with lower specificities.

Quantitative SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM.

BACKGROUND: This study aimed to evaluate the predictive and monitoring role of somatostatin receptor (SSTR) positron emission tomography-computed tomography (PET/CT) and clinical parameters in patients with neuroendocrine liver metastases (NELM) from pancreatic neuroendocrine tumors (pNET) receiving capecitabine and temozolomide (CAPTEM). PATIENTS AND METHODS: This retrospective study included twenty-two patients with pNET and NELM receiving CAPTEM who underwent pre- and post-therapeutic 68Ga-DOTATATE/-TOC PET/CT. Imaging (including standardized uptake value [SUV] of target lesions [NELM and pNET], normal spleen and liver) and clinical (Chromogranin A [CgA], Ki-67) parameters were assessed. Treatment outcome was evaluated as response according to RECIST 1.1, progression free survival (PFS) and overall survival (OS). RESULTS: The median PFS (mPFS) was 7 months. Responders had a significantly longer mPFS compared to non-responders (10 vs. 4 months p = 0.022). Median OS (mOS) was 33 months (mOS: responders = 80 months, non-responders = 24 months p = 0.182). Baseline imaging showed higher SUV in responders, including absolute SUV, tumor-to-spleen (T/S), and tumor-to-liver (T/L) ratios (p < 0.02). All SUV parameters changed only in the responders during follow-up. Univariable Cox regression analysis identified baseline Tmax/Smean ratio and percentage change in size of pNETs as significant factors associated with PFS. A baseline Tmax/Smean ratio < 1.5 was associated with a shorter mPFS (10 vs. 4 months, (p < 0.05)). Prognostic factors for OS included age, percentage change in CgA and in T/S ratios in univariable Cox regression. CONCLUSIONS: SSTR-PET/CT can be useful for predicting response and survival outcomes in pNET patients receiving CAPTEM: Higher baseline SUV values, particularly Tmax/Smean ratios of liver metastases were associated with better response and prolonged PFS.

Investigation of image-based lesion and kidney dosimetry protocols for 177Lu-PSMA-I&T therapy with and without a late SPECT/CT acquisition.

BACKGROUND: 177Lu-PSMA therapy has been successfully used to prolong the survival of patients with metastatic castration-resistant prostate cancer. Patient-specific dosimetry based on serial quantitative SPECT/CT imaging can support the understanding of dose-effect relationships. However, multiple SPECT/CT measurements can be challenging for patients, which motivates the investigation of efficient sampling schedules and their impact on dosimetry. In this study, different time samplings with respect to the number and timing of SPECT/CT acquisitions with and without a late measurement were investigated. MATERIALS AND METHODS: In total, 43 lesions and 10 kidneys of 5 patients receiving 177Lu-PSMA-I&T therapy were investigated. Whole-body SPECT/CT measurements were performed at 1, 2, 3 and 7 days post-injection. For both lesions (isocontour-based segmentation) and kidneys (CT-based segmentation), a reference model was employed including all four time points. To identify the best-matching fit function out of a pre-defined set of models, visual inspection, coefficients of variation and sum of squared errors were considered as goodness-of-fit criteria. Biologically effective doses (BEDs) calculated with different time samplings (days 1, 2, 3/1, 2, 7/1, 3, 7/2, 3, 7 and 1, 2/1, 3/1, 7) were compared to the reference. RESULTS: The best-fit function was found to be a mono-exponential model for lesions and a bi-exponential model with a population-based parameter and two free parameters for kidneys. The BEDs calculated with the time sampling 1, 3, 7 days showed the lowest deviations from the reference for lesions with 4 ± 5%. Without day 7, still 86% of all lesions showed deviations from the reference < 10%. The outlier deviations showed a positive correlation with the effective half-life of the respective lesions. For kidneys, including days 1, 2, 3 achieved the best results with 0 ± 1%. Generally, deviations for kidneys were found to be small for all time samplings (max. 13%). CONCLUSIONS: For combined optimization of the SPECT/CT time sampling for kidney and lesion dosimetry during 177Lu-PSMA-I&T therapy, the sampling with days 1, 3, 7 showed the smallest deviation from the reference. Without a late acquisition, using the schedule with days 1, 2, 3 is likewise feasible.

Primary presentation and clinical course of pediatric and adolescent patients with differentiated thyroid carcinoma after radioiodine therapy.

Introduction: Differentiated thyroid carcinoma (DTC) in childhood and during adolescence is extremely rare. Pediatric DTC commonly presents with advanced disease at diagnosis including a high prevalence of cervical lymph node metastases and pulmonary metastases. Studies in children with DTC are limited. Therefore, we aimed to evaluate the initial presentation, effectiveness of radioiodine therapy (RIT), and long-term outcome of prepubertal in comparison to pubertal/postpubertal patients. Methods: Eighty-five pediatric and young patients aged 6.4 to 21.9 years with histopathologically confirmed DTC were retrospectively included. They all underwent total thyroidectomy followed by RIT. Initial presentation and outcome of prepubertal and pubertal/postpubertal patients were compared 1 year after RIT, during follow-up, and at the last visit of follow-up. Results: Prepubertal patients presented with significantly higher T and M stages. One year after RIT, 42/81 (52%) patients still presented with evidence of disease (ED). During follow-up of a median of 7.9 years, prepubertal patients were less often in complete remission (58% vs. 82% in pubertal patients). At the last visit of follow-up, 19/80 (24%) patients still had ED without statistical differences between the two groups (42% prepubertal vs. 18% pubertal/postpubertal, p-value 0.06). None of our patients died disease-related over the observed period. Conclusion: Prepubertal children with DTC presented with a more advanced tumor stage at the initial presentation. During follow-up, they present more often with ED. However, at the end of our study, we did not observe statistically relevant differences in patient outcomes between the prepubertal and pubertal/postpubertal groups.