Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma: Association with Metabolic Tumor Burden Determined with FDG-PET/CT.

BACKGROUND: The detection of circulating tumor DNA (ctDNA) with next-generation sequencing (NGS) in venous blood is a promising tool for the genomic profiling of head and neck squamous cell carcinoma (HNSCC). The association between ctDNA findings and metabolic tumor burden detected with FDG-PET/CT imaging is of particular interest for developing prognostic and predictive algorithms in HNSCC. METHODS: Twenty-six prospectively enrolled HNSCC patients were eligible for further analysis. All patients underwent tumor tissue and venous liquid biopsy sampling and FDG-PET/CT before definitive oncologic treatment. An NGS-based commercial panel was used for a genomic analysis of the samples. RESULTS: Maximum variant allele frequency (VAF) in blood correlated positively with whole-body (WB) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (r = 0.510, p = 0.008 and r = 0.584, p = 0.002, respectively). A positive liquid biopsy was associated with high WB-TLG using VAF ≥ 1.00% or ≥5.00% as a cut-off value (p = 0.006 or p = 0.003, respectively). Additionally, ctDNA detection was associated with WB-TLG when only concordant variants detected in both ctDNA and tissue samples were considered. CONCLUSIONS: A high metabolic tumor burden based on FDG imaging is associated with a positive liquid biopsy and high maximum VAF. Our findings suggest a complementary role of metabolic and genomic signatures in the pre-treatment evaluation of HNSCC.

Detection of prostate cancer bone metastases with fast whole-body 99mTc-HMDP SPECT/CT using a general-purpose CZT system.

BACKGROUND: We evaluated the effects of acquisition time, energy window width, and matrix size on the image quality, quantitation, and diagnostic performance of whole-body 99mTc-HMDP SPECT/CT in the primary metastasis staging of prostate cancer. METHODS: Thirty prostate cancer patients underwent 99mTc-HMDP SPECT/CT from the top of the head to the mid-thigh using a Discovery NM/CT 670 CZT system with list-mode acquisition, 50-min acquisition time, 15% energy window width, and 128 × 128 matrix size. The acquired list-mode data were resampled to produce data sets with shorter acquisition times of 41, 38, 32, 26, 20, and 16 min, narrower energy windows of 10, 8, 6, and 4%, and a larger matrix size of 256 × 256. Images were qualitatively evaluated by three experienced nuclear medicine physicians and quantitatively evaluated by noise, lesion contrast and SUV measurements. Diagnostic performance was evaluated from the readings of two experienced nuclear medicine physicians in terms of patient-, region-, and lesion-level sensitivity and specificity. RESULTS: The originally acquired images had the best qualitative image quality and lowest noise. However, the acquisition time could be reduced to 38 min, the energy window narrowed to 8%, and the matrix size increased to 256 × 256 with still acceptable qualitative image quality. Lesion contrast and SUVs were not affected by changes in acquisition parameters. Acquisition time reduction had no effect on the diagnostic performance, as sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve were not significantly different between the 50-min and reduced acquisition time images. The average patient-level sensitivities of the two readers were 88, 92, 100, and 96% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 78, 84, 84, and 78%. The average region-level sensitivities of the two readers were 55, 58, 59, and 56% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 95, 98, 96, and 95%. The number of equivocal lesions tended to increase as the acquisition time decreased. CONCLUSION: Whole-body 99mTc-HMDP SPECT/CT can be acquired using a general-purpose CZT system in less than 20 min without any loss in diagnostic performance in metastasis staging of high-risk prostate cancer patients.

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Lateralization in 11 C-Metomidate PET and outcome of adrenalectomy in primary aldosteronism.

INTRODUCTION: Subtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone 11 C-metomidate positron emission tomography (11 C-MTO-PET) for subtype classification. METHODS: Postoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative 11 C-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on 11 C-MTO-PET alone and those with concordant or discordant lateralization in 11 C-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure. RESULTS: Adrenalectomy side was based on 11 C-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after 11 C-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant 11 C-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with 11 C-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery. CONCLUSIONS: Outcomes of adrenalectomy based on clinically significant lateralization in 11 C-MTO-PET alone correspond to those based on 11 C-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with 11 C-MTO-PET in case of discordant lateralization studies.

Bioactive glass granules versus standard autologous and allogeneic bone grafts: a randomized trial of 49 adult bone tumor patients with a 10-year follow-up.

BACKGROUND AND PURPOSE: As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS: 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS: At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION: BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.

68Ga-Citrate PET of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates.

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy men. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with good manufacturing practices. Six healthy men (age 41 ± 12 y, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging, and the radioactivity concentration was measured with a γ-counter. Urinary voids were collected and measured. The MIRD bladder-voiding model with a 3.5-h voiding interval was used. A model using a 70-kg adult man and the MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM software, version 2.0. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3-h measuring period. Although radioactivity excretion via urine was rather slow (biologic half-time, 69 ± 24 h), the highest decay-corrected concentrations in urinary bladder contents were measured at the 90- and 180-min time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose, 0.077 ± 0.008 mSv/MBq. The mean effective dose (International Commission on Radiological Protection publication 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200-MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.

Comparison of reprojected bone SPECT/CT and planar bone scintigraphy for the detection of bone metastases in breast and prostate cancer.

OBJECTIVE: The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. METHODS: Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent 99mTc-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and 18F-NaF or 18F-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. RESULTS: All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. CONCLUSION: Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

Association between bone mineral metabolism and vascular calcification in end-stage renal disease.

BACKGROUND: Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism. METHODS: Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 - L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score. RESULTS: This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured. CONCLUSIONS: The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov protocol registration and result system, ID is NCT02967042 . Date of registration is 17/11/2016.

Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer.

PURPOSE OF THE REPORT: The aim of this study was to evaluate the distribution of hypoxia using 18F-EF5 as a hypoxia tracer in cervical cancer patients with PET/MRI. We investigated the association between this 18F-EF5-PET tracer and the immunohistochemical expression of endogenous hypoxia markers: HIF1α, CAIX, and GLUT1. PATIENTS AND METHODS: Nine patients with biopsy-proven primary squamous cell cervix carcinoma (FIGO 2018 radiological stages IB1-IIIC2r) were imaged with dual tracers 18F-EF5 and 18F-FDG using PET/MRI (Int J Gynaecol Obstet. 2019;145:129-135). 18F-EF5 images were analyzed by calculating the tumor-to-muscle ratio to determine the hypoxic tissue (T/M ratio >1.5) and further hypoxic subvolume (HSV) and percentage hypoxic area. These 18F-EF5 hypoxic parameters were correlated with the size and localization of tumors in 18F-FDG PET/MRI and the results of hypoxia immunohistochemistry. RESULTS: All primary tumors were clearly 18F-FDG and 18F-EF5 PET positive and heterogeneously hypoxic with multiple 18F-EF5-avid areas in locally advanced cancer and single areas in clinically stage I tumors. The location of hypoxia was detected mainly in the periphery of tumor. Hypoxia parameters 18F-EF5 max T/M ratio and HSV in primary tumors correlated independently with the advanced stage (P = 0.036 and P = 0.040, respectively), and HSV correlated with the tumor size (P = 0.027). The location of hypoxia in 18F-EF5 imaging was confirmed with a higher hypoxic marker expression HIF1α and CAIX in tumor fresh biopsies. CONCLUSIONS: The 18F-EF5 imaging has promising potential in detecting areas of tumor hypoxia in cervical cancer.

Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy.

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover. 18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a 18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche's historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1-L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, 18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Long-term Results of Microvascular Lymph Node Transfer: Correlation of Preoperative Factors and Operation Outcome.

Our objective was to analyze whether a correlation could be observed between preoperative factors and microvascular lymph node transfer outcome after long-term follow-up. METHODS: We included 67 patients in this retrospective case series. The incidence of cellulitis, the difference of arm circumference, the use of the compression garments both preoperatively and postoperatively, and subjective symptoms, such as pain, were analyzed. Volumetry and lymphoscintigraphy results were also analyzed in a subgroup of patients. We correlated preoperative factors with postoperative results. RESULTS: After 70 ± 17 months of follow-up, 42% of the patients were able to discontinue the use of compression garments. The subjective pain symptoms were reduced in 75% of the patients. The incidence of cellulitis was reduced from preoperative 0.20 ± 0.55/y to postoperative 0.02 ± 0.08/y. As a novel finding, the patients with preoperative cellulitis were more likely to continue the use of the compression garments. CONCLUSIONS: The surgery is beneficial to most studied lymphedema patients, although it is not the cure for all patients. The incidence of cellulitis was reduced, and further, the presence of preoperative cellulitis seems to affect the outcome of the operation.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

18F-FDG positron emission tomography/computed tomography of cardiac implantable electronic device infections.

BACKGROUND: The diagnosis of cardiac implantable electronic device (CIED) infection is challenging because of its variable presentations. We studied the value of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the detection of CIED infection. METHODS AND RESULTS: Thirty patients with suspected CIED infection underwent 18F-FDG-PET/CT. The control group was ten patients with asymptomatic CIED who underwent cancer-related 18F-FDG-PET/CT. 18F-FDG-PET/CT was evaluated visually, semiquantitatively as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). Final diagnosis of CIED infection was based on clinical and bacteriological data. 18F-FDG-PET/CT was visually positive in all 9 patients with recent (≤ 8 weeks) implantation of CIED, but only 4 had confirmed CIED infection. 18F-FDG-PET/CT was true positive in 9 out of 21 cases with remote implantation of CIED and false positive in 3 (14.3%) cases. 18F-FDG-PET/CT was also false positive in 3 (30%) cases of control group. The SUVmax of the pocket area was significantly higher in patients with CIED infection than in the control group (4.8 ± 2.4 vs 2.0 ± .8, P < .001). By using the cut-off value of TBR ≥ 1.8, sensitivity of 18F-FDG-PET/CT for the diagnosis of CIED infection in patients with remote implantation was 90% and specificity 73%, PPV 75%, and NPV 89%. CONCLUSIONS: 18F-FDG-PET/CT is a sensitive but nonspecific method in the diagnosis of CIED infection.

Functional imaging with 11C-metomidate PET for subtype diagnosis in primary aldosteronism.

OBJECTIVE: Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA. DESIGN: We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery. METHODS: Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2. RESULTS: In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma. CONCLUSIONS: The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.

The feasibility of [18F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study.

RATIONALE: Evaluation of the feasibility of [18F]EF5-PET/CT scan in identifying hypoxic lesions in ovarian tumors in prospective clinical setting. METHODS: Fifteen patients with a suspected malignant ovarian tumor were scanned with [18F]EF5 and [18F]FDG-PET/CT preoperatively. The distribution of [18F]EF5-uptake, total intraabdominal metabolic tumor volume (TMTV), and hypoxic subvolume (HSV) were assessed. RESULTS: [18F]EF5-PET/CT suggested hypoxia in 47% (7/15) patients. The median HSV was 87 cm3 (31% of TMTV). The [18F]EF5-uptake was detected in primary tumors and in four patients also in intra-abdominal metastases. The [18F]EF5-uptake in cancer tissue was low compared to physiological excretory pathways, complicating the interpretation of PET/CT images. CONCLUSIONS: [18F]EF5-PET/CT is not feasible in ovarian cancer imaging in clinical setting due to physiological intra-abdominal [18F]EF5-accumulation. However, it may be useful when used complementarily to FDG-PET/CT.

Correlation between 18F-Sodium Fluoride positron emission tomography and bone histomorphometry in dialysis patients.

BACKGROUND: The diagnosis of renal osteodystrophy is challenging. Bone biopsy is the gold standard, but it is invasive and limited to one site of the skeleton. The ability of biomarkers to estimate the underlying bone pathology is limited. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a noninvasive quantitative imaging technique that allows assessment of regional bone turnover at clinically relevant sites. The hypothesis of this study was, that 18F-NaF PET correlates with bone histomorphometry in dialysis patients and could act as a noninvasive diagnostic tool in this patient group. METHODS: This was a cross-sectional diagnostic test study. 26 dialysis patients with biochemical abnormalities indicating mineral and bone disorder were included. All the participants underwent a 18F-NaF PET scan and a bone biopsy. Fluoride activity in the PET scan was measured in the lumbar spine and at the anterior iliac crest. Dynamic and static histomorphometric parameters of the bone biopsy were assessed. As histomorphometric markers for bone turnover we used bone formation rate per bone surface (BFR/BS) and activation frequency per year (Ac.f). RESULTS: There was a statistically significant correlation between fluoride activity in the 18F-NaF PET scan and histomorphometric parameters such as bone formation rate, activation frequency and osteoclast and osteoblast surfaces and mineralized surfaces. 18F-NaF PET's sensitivity to recognize low turnover in respect to non-low turnover was 76% and specificity 78%. Because of the small number of patients with high turnover, we were unable to demonstrate significant predictive value in this group. CONCLUSIONS: A clear correlation between histomorphometric parameters and fluoride activity in the 18F-NaF PET scan was established. 18F-NaF PET may possibly be a noninvasive diagnostic tool in dialysis patients with low turnover bone disease, but further research is needed.

PET/CT for Evaluation of Ovarian Cancer.

Ovarian cancer is the leading cause of death from gynecologic cancer in the developed countries. It is usually diagnosed in advanced stage since it is often symptomless or symptoms are nonspecific in early course of the disease. It has a high recurrence rate and poor prognosis in advanced disease. Ovarian cancer has distinct type of disease spread in abdomen and above diaphragm. Surgery is irreplaceable in staging but multimodality imaging approach is often needed during the diagnosis, treatment monitoring, and follow-up of patients with ovarian cancer, typically ultrasound, CT, MRI and PET/CT are the main modalities used. The current clinical role of PET/CT in evaluation of ovarian cancer during staging, treatment prognostication and response assessment, and in disease recurrence is discussed in this review compared to conventional imaging.

Bupropion Causes Misdiagnosis in Brain Dopamine Transporter Imaging for Parkinsonism.

OBJECTIVE: The objective of this study was to report long-lasting effects of bupropion on brain dopamine transporter (DAT) in a patient with depression and parkinsonism. METHODS: The patient was a 52-year old man who had been treated with 150 mg/d of bupropion for depression. The patient developed cognitive problems, bradykinesia, and reduced stride length for which he was scanned with [I]FP-CIT single photon emission computed tomography after the recommended 1-week discontinuation of bupropion. Levodopa treatment trial was initiated without a response. Eleven months later, the patient was scanned for a second time after a 1-month stoppage of bupropion. RESULTS: The first scan was abnormal with left putamen specific binding ratio of 1.99 (SDs from the reference value mean, -2.40), right putamen of 2.27 (SD, -1.84), left caudate of 2.33 (SD, -2.26), and right caudate of 2.29 (SD, -2.18). The second scan (after 1-month discontinuation) was normal, and specific binding ratios had increased from 5.2% to 31.7% in all striatal regions as compared with the first scan. Brain magnetic resonance imaging and [F]fluorodeoxyglucose positron emission tomography imaging were normal, and there was no levodopa response or other features supporting neurodegenerative parkinsonism. CONCLUSIONS: Bupropion has previously generally been discontinued 1 week prior DAT imaging, which meets the recommended, albeit arbitrary, time interval of 5 plasma clearance half-lives before the scan. One-week discontinuation of bupropion before DAT imaging may be insufficiently short. Our case shows that longer medication washout and rescan may be needed when there is contradiction between the imaging result and clinical outcome in patients with medications affecting DAT binding.