Evaluating F-18-PSMA-1007-PET in primary prostate cancer and comparing it to multi-parametric MRI and histopathology.

BACKGROUND: PSMA-PET is a novel imaging modality for the staging of prostate cancer (PCa). While there are several PSMA ligands available, F-18-PSMA-1007 is particularly of interest as it is not renally excreted and therefore does not impair the imaging of the pelvic area. Hence, this study aimed to investigate the F-18-PSMA-1007-PET for the primary staging of PCa and compared it to multi-parametric (mp) MRI and histopathology. METHODS: A retrospective study was performed of men with intermediate and high-risk PCa patients that underwent a F-18-PSMA-1007-PET after mpMRI with subsequent MR-guided target biopsy (MRGB). Suspicious mpMRI lesions and F-18-PSMA-1007-PET were simultaneously reviewed on both a per patient and per-lesion basis. Results were subsequently evaluated with histopathological outcome of MRGB, and if performed, the radical prostatectomy specimen. RESULTS: A total of 66 suspicious mpMRI lesions were identified in 53 patients and underwent MRGB. Two lesions had a maximum standardized uptake value (SUVmax) less than the mean SUVmax of healthy prostate tissue and were considered as non-PSMA-expressing. All PSMA avid tumors had higher SUVmax than the mean SUVmean of the bladder/urine, therefore all lesions were clearly distinguishable in the pelvic area. Twenty-three patients received a radical prostatectomy of which the histopathology specimens were evaluated. F-18-PSMA-1007-PET/CT correctly staged seminal vesicle invasion (i.e. pT3b) more often than mpMRI (90 vs. 76%), whereas mpMRI more accurately detected extracapsular extension (i.e. pT3a) compared to F-18-PSMA-1007-PET (90% vs 57%). CONCLUSIONS: The present study of a selected cohort suggest that dual imaging with mpMRI and F-18-PSMA-1007-PET may improve staging of primary PCa. F-18-PSMA-1007-PET/CT had low renal clearance, which could assist the evaluation of tumors in proximity of the bladder.

Renal sympathetic denervation in patients with vasospastic angina.

BACKGROUND: Sympathetic overactivity has been linked to vasospastic angina (VSA), although the exact pathophysiology of VSA is poorly understood. The purpose of this study is to assess if renal sympathetic denervation (RDN) reduces cardiac sympathetic nerve activity with a subsequent beneficial effect on angina relief in patients with refractory VSA. METHODS AND RESULTS: Cardiac sympathetic nerve activity was assessed prior to procedure and at 6 months post-procedure using iodine-123 labeled meta-iodobenzylguanidine (123I-MIBG) imaging. The Seattle Angina questionnaire (SAQ) was used to assess the degree to which the disease impacts quality of life. No significant change was observed in early HMR (pre-RDN: 2.74 [2.10 to 3.21] vs 6 months post-RDN: 2.57 [2.20 to 3.00]; P = 0.76), and late HMR (pre-RDN: 2.56 [2.18 to 3.20] vs 6 months post-RDN: 2.36 [2.13 to 3.22]; P = 0.22). Additionally, no change was seen in WR (P = 0.22). SAQ results revealed significant improvements in perceived physical limitation, angina frequency, and quality of life at 6 months (P < 0.05 for all). CONCLUSION: RDN resulted in improvements in angina class and quality of life at 6 months in patients with refractory VSA. RDN, however, did not result in significant changes in cardiac sympathetic nerve activity as measured using 123I-MIBG. The latter observation should be considered with caution given the small sample size of this study. Larger studies are needed to assess this further.

Bridging the Imaging Gap: PSMA PET/CT Has a High Impact on Treatment Planning in Prostate Cancer Patients with Biochemical Recurrence-A Narrative Review of the Literature.

68Ga- and 18F-labeled prostate-specific membrane antigen (PSMA) molecules have created new opportunities for the unmet diagnostic needs in prostate cancer. The purpose of this article is to give an overview of studies that have examined the role of PSMA PET in treatment planning for prostate cancer patients with biochemical recurrence (BCR). Methods: Medline, Embase, Web of Science, Google Scholar, and Cochrane Central were searched for relevant articles. After excluding the articles that did not fulfill the required criteria, we included in this review 12 publications that reported the impact of PSMA PET on the treatment plan for prostate cancer patients with BCR. Results: All studies in our review emphasized the impact of PSMA PET images on therapy management in prostate cancer patients with BCR. Overall, the impact of PSMA PET/CT on therapy management varied between 30% and 76% among the 1,346 patients included in the review. Upstaging was reported in 32%-67% of the patients. Patients with low prostate-specific antigen values (<0.5 ng/mL) also demonstrated positive lesions, which could not have been detected by means of conventional imaging techniques. Important modifications to the original treatment plan included avoidance of systemic therapy (17%-40%) and PET-directed local therapy (in ≤60% of the patients). Conclusion: PSMA imaging demonstrated a high clinical impact in patients with BCR, with modifications to the original treatment plan occurring among half the patients. Detecting recurrence in BCR can prevent unnecessary toxicity and lead to individualized therapy.

18F-fluorodeoxyglucose positron emission/computed tomography and computed tomography angiography in prosthetic heart valve endocarditis: from guidelines to clinical practice.

The timely diagnosis of prosthetic heart valve endocarditis remains challenging yet of utmost importance. 18F-fluorodeoxyglucose (18 F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) were recently introduced as additional diagnostic tools in the most recent ESC guidelines on infective endocarditis. However, how to interpret PET/CT findings with regard to what is to be considered abnormal, what the potential confounders may be, as well as which patients benefit most from these additional imaging techniques and how to best perform them in these often-complex patients, remains unclear. This review focusses on factors regarding patient selection and image acquisition that need to be taken into account when employing 18F-FDG PET/CT and CTA in daily clinical practice, and the importance of a multidisciplinary Endocarditis Team herein. Furthermore, it emphasizes the need for standardized acquisition protocols and image interpretation, especially now that these techniques are starting to be widely embraced by the cardiovascular society.

Optimizing labelling conditions of 213Bi-DOTATATE for preclinical applications of peptide receptor targeted alpha therapy.

BACKGROUND: 213Bismuth (213Bi, T1/2 = 45.6 min) is one of the most frequently used α-emitters in cancer research. High specific activity radioligands are required for peptide receptor radionuclide therapy. The use of generators containing less than 222 MBq 225Ac (actinium), due to limited availability and the high cost to produce large-scale 225Ac/213Bi generators, might complicate in vitro and in vivo applications though.Here we present optimized labelling conditions of a DOTA-peptide with an 225Ac/213Bi generator (< 222 MBq) for preclinical applications using DOTA-Tyr3-octreotate (DOTATATE), a somatostatin analogue. The following labelling conditions of DOTATATE with 213Bi were investigated; peptide mass was varied from 1.7 to 7.0 nmol, concentration of TRIS buffer from 0.15 mol.L-1 to 0.34 mol.L-1, and ascorbic acid from 0 to 71 mmol.L-1 in 800 µL. All reactions were performed at 95 °C for 5 min. After incubation, DTPA (50 nmol) was added to stop the labelling reaction. Besides optimizing the labelling conditions, incorporation yield was determined by ITLC-SG and radiochemical purity (RCP) was monitored by RP-HPLC up to 120 min after labelling. Dosimetry studies in the reaction vial were performed using Monte Carlo and in vitro clonogenic assay was performed with a rat pancreatic tumour cell line, CA20948. RESULTS: At least 3.5 nmol DOTATATE was required to obtain incorporation ≥ 99 % with 100 MBq 213Bi (at optimized pH conditions, pH 8.3 with 0.15 mol.L-1 TRIS) in a reaction volume of 800 µL. The cumulative absorbed dose in the reaction vial was 230 Gy/100 MBq in 30 min. A minimal final concentration of 0.9 mmol.L-1 ascorbic acid was required for ~100 MBq (t = 0) to minimize radiation damage of DOTATATE. The osmolarity was decreased to 0.45 Osmol/L.Under optimized labelling conditions, 213Bi-DOTATATE remained stable up to 2 h after labelling, RCP was ≥ 85 %. In vitro showed a negative correlation between ascorbic acid concentration and cell survival. CONCLUSION: 213Bismuth-DOTA-peptide labelling conditions including peptide amount, quencher and pH were optimized to meet the requirements needed for preclinical applications in peptide receptor radionuclide therapy.

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Cost-effectiveness of adding FDG-PET or CT to the diagnostic work-up of patients with stage III melanoma.

OBJECTIVE: The aim of this prospective study was to assess predictive value of fludeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) and to analyze their cost-effectiveness in several diagnosis-treatment combinations. BACKGROUND: The incidence of melanoma continues to rise. A proportion will present or recur with lymph node metastases (American Joint Committee on Cancer/Union for International Cancer Control stage III). To detect distant metastases, CT and/or FDG-PET are available. However, few studies have assessed their value and costs in stage III. METHODS: All consecutive patients with melanoma with palpable, proven lymph node metastases (2003-2008) referred for examination with FDG-PET and CT were prospectively included. Sensitivity, specificity, and accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated. In economic evaluation, the costs of diagnostic work-up with and without FDG-PET and CT were compared. RESULTS: Overall, 253 patients with melanoma were included. FDG-PET showed a higher sensitivity than CT: 86.1% compared with 78.2%. Specificity was higher for CT (93.7%) compared with FDG-PET (93.1%). Overall, FDG-PET showed a higher PPV and NPV. Cost-consequence analysis showed that adding CT (True-Positive upstaging in 61 patients) to diagnostic work-up decreased cost by 5.5%, adding FDG-PET (True-Positive upstaging in 68 patients) increased cost by 7.2%, and adding both (True-Positive upstaging in 78 patients) increased cost by 15.1%. CONCLUSIONS: In this study, FDG-PET had higher sensitivity and predictive value, whereas CT had a higher specificity. Adding one of these diagnostic tools improved the staging of stage III patients with less than 10% cost increase. A proposal for stage-specific use of imaging modalities for clinicians caring for patients with melanoma is presented.

(18)F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis.

PURPOSE: Bronchoalveolar lavage (BAL) and (18)F-fluorodeoxyglucose ((18)F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by (18)F-FDG PET represents signs of disease activity as reflected by BAL, (18)F-FDG PET patterns were compared with BAL cell profiles. METHODS: In this retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients underwent BAL and (18)F-FDG PET. Based on (18)F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A) and activity in the lung parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils (%) were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUV(max)). Additionally, SUV(max) and BAL parameters per radiographic stage were analysed. RESULTS: Overall, the SUV(max) in the lung parenchyma correlated with neutrophils and SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio. In both groups, a significant, negative correlation between the SUV(max) of the mediastinum/hila and the CD103(+)CD4(+)/CD4(+) ratio was found. In group B, the SUV(max) of the mediastinum/hila correlated with the CD4/CD8 ratio, while the SUV(max) in the lung parenchyma correlated with the CD103(+)CD4(+)/CD4(+) ratio and neutrophils. Significant differences were found in the SUV(max), CD4/CD8 ratio, CD103(+)CD4(+)/CD4(+) ratio and neutrophils between the radiographic stages. The SUV(max) of the lung parenchyma was positively related to the radiographic stage, while the SUV(max) of the mediastinum/hila and CD4/CD8 ratio were inversely related. CONCLUSION: (18)F-FDG PET correlates with the CD4/CD8 ratio and neutrophils, suggesting that (18)F-FDG PET represents this specific cell profile in BAL. High SUV(max) values of the lung parenchyma may therefore correlate with more severe parenchymal involvement, particularly when accompanied by a low SUV(max) of the mediastinum/hila.

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0.

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.

Small field-of-view dedicated cardiac SPECT systems: impact of projection truncation.

PURPOSE: Small field-of-view (FOV) dedicated cardiac SPECT systems suffer from truncated projection data. This results in (1) neglect of liver activity that otherwise could be used to estimate (and subsequently correct) the amount of scatter in the myocardium by model-based scatter correction, and (2) distorted attenuation maps. In this study, we investigated to what extent truncation impacts attenuation correction and model-based scatter correction in the cases of (99m)Tc, (201)Tl, and simultaneous (99m)Tc/(201)Tl studies. In addition, we evaluated a simple correction method to mitigate the effects of truncation. METHODS: Digital thorax phantoms of different sizes were used to simulate the full FOV SPECT projections for (99m)Tc, (201)Tl, and simultaneous (99m)Tc/(201)Tl studies. Small FOV projections were obtained by artificially truncating the full FOV projections. Deviations from ideal heart positioning were simulated by axially shifting projections resulting in more severe liver truncation. Effects of truncation on SPECT images were tested for ordered subset (OS) expectation maximization reconstruction with (1) attenuation correction and detector response modelling (OS-AD), and (2) with additional Monte-Carlo-based scatter correction (OS-ADS). To correct truncation-induced artefacts, we axially extended truncated projections on both sides by duplicating pixel values on the projection edge. RESULTS: For both (99m)Tc and (201)Tl, differences in the reconstructed myocardium between full FOV and small FOV projections were negligible. In the nine myocardial segments, the maximum deviations of the average pixel values were 1.3% for OS-AD and 3.5% for OS-ADS. For the simultaneous (99m)Tc/(201)Tl studies, reconstructed (201)Tl SPECT images from full FOV and small FOV projections showed clearly different image profiles due to truncation. The maximum deviation in defected segments was found to be 49% in the worst-case scenario. However, artificially extending projections reduced deviations in defected segments to a few percent. CONCLUSION: Our results indicate that, for single isotope studies, using small FOV systems has little impact on attenuation correction and model-based scatter correction. For simultaneous (99m)Tc/(201)Tl studies, artificial projection extension almost fully eliminates the adverse effects of projection truncation.

18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis.

PURPOSE: Angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) are serological markers, widely used for determining sarcoidosis activity. (18)F-FDG PET has proven to be a sensitive technique in the imaging of sarcoidosis. The aim of this study was to determine sensitivity of (18)F-FDG PET, genotype-corrected ACE and sIL-2R in active sarcoidosis as well as their correlation. METHODS: This retrospective study included 36 newly diagnosed, symptomatic sarcoidosis patients. ACE and sIL-2R levels were simultaneously obtained within 4 weeks of (18)F-FDG PET. ACE was corrected for genotype and expressed as Z-score. (18)F-FDG PET was visually evaluated and scored as positive or negative. Maximum and average standardized uptake values (SUV(max) and SUV(avg)) were compared with ACE and sIL-2R. RESULTS: (18)F-FDG PET was found positive in 34 of 36 patients (94%). Thirteen patients (36%) showed an increased ACE with the highest sensitivity found in patients with the I/I genotype (67%). Seventeen patients (47%) showed an increased sIL-2R. No correlation was found between SUV and ACE or sIL-2R. Increased ACE and sIL-2R correlated with a positive (18)F-FDG PET in 12 patients (92%) and 16 patients (94%), respectively. CONCLUSION: (18)F-FDG PET is a very sensitive technique to assess active sarcoidosis, in contrast with ACE and sIL-2R, suggesting a pivotal role for (18)F-FDG PET in future sarcoidosis assessment.

Imaging of fibrogenesis in patients with idiopathic pulmonary fibrosis with cis-4-[(18)F]-Fluoro-L: -proline PET.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which no single diagnostic modality is able to evaluate the activity of the disease process. Cis-4-(18)F-fluoro-L: -proline ((18)F-proline) was shown in animal studies to be a reliable marker for fibrosis formation. We tested this candidate radioligand for imaging of fibrogenesis in patients with IPF. METHODS: Five patients with IPF proven by lung biopsy and computed tomography were included. Furthermore, we also included one patient with non-specific interstitial pneumonia (NSIP) and scleroderma and one with NSIP and organising pneumonia. Positron emission tomography (PET) acquisition was performed 1, 2 and 3h after injection of 400MBq (18)F-proline. We scored (18)F-proline activity visually and quantitatively by calculating the activity in the regions of interest over lung, liver and mediastinum. RESULTS: We found low uptake of (18)F-proline in the lungs of all patients with IPF. The highest uptake was seen at 2h post-injection, with a decline at 3h past injection. The differences in lung uptake between patients were small, except for one patient with NSIP and organising pneumonia who had a slightly higher (18)F-proline uptake. No significant correlations between (18)F-proline uptake and clinical parameters were found. CONCLUSIONS: Due to the low pulmonary uptake of (18)F-proline in patients with IPF, (18)F-proline does not seem to be a suitable radioligand to evaluate the activity of fibrosis formation in patients with IPF. The low uptake in the lungs of patients with interstitial fibrosis may be explained by the slow nature of fibrogenesis or to the relatively low dose of proline that can be used.

The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials.

INTRODUCTION: Several studies have shown the usefulness of positron emission tomography (PET) quantification using standardised uptake values (SUV) for diagnosis and staging, prognosis and response monitoring. Many factors affect SUV, such as patient preparation procedures, scan acquisition, image reconstruction and data analysis settings, and the variability in methodology across centres prohibits exchange of SUV data. Therefore, standardisation of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) PET whole body procedures is required in multi-centre trials. METHODS: A protocol for standardisation of quantitative FDG whole body PET studies in the Netherlands (NL) was defined. This protocol is based on standardisation of: (1) patient preparation; (2) matching of scan statistics by prescribing dosage as function of patient weight, scan time per bed position, percentage of bed overlap and image acquisition mode (2D or 3D); (3) matching of image resolution by prescribing reconstruction settings for each type of scanner; (4) matching of data analysis procedure by defining volume of interest methods and SUV calculations and; (5) finally, a multi-centre QC procedure is defined using a 20-cm diameter phantom for verification of scanner calibration and the NEMA NU 2 2001 Image Quality phantom for verification of activity concentration recoveries (i.e., verification of image resolution and reconstruction convergence). DISCUSSION: This paper describes a protocol for standardization of quantitative FDG whole body multi-centre PET studies. CONCLUSION: The protocol was successfully implemented in the Netherlands and has been approved by the Netherlands Society of Nuclear Medicine.