18F-DCFPyL PET/CT for primary staging in 160 high-risk prostate cancer patients; metastasis detection rate, influence on clinical management and preliminary results of treatment efficacy.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT shows better diagnostic performance for detection of lymph node and bone metastases as compared to conventional imaging. Studies of PSMA PET/CT in primary staging comprise highly selected patient cohorts. This study evaluates 18F-DCFPyL PET/CT as first-line imaging modality for primary staging of high-risk prostate cancer. MATERIAL: From February 2018 until April 2019, all patients with high-risk prostate cancer received 18F-DCFPyL PET/CT for staging of prostate cancer. Baseline characteristics, findings at 18F-DCFPyL PET/CT, number and type of required additional diagnostic procedures, findings at additional diagnostic procedures, and effects of therapy on PSA levels for all patients treated with curative intent were collected and evaluated. RESULTS: One hundred-sixty patients were included in the study of which 90 (56%) had evidence of metastasized disease (N1, M1a, M1b and, M1c in 49%, 28%, 31%, and 3% respectively). Additional diagnostic imaging was needed in 2/160 patients (1%) because of equivocal findings on 18F-DCFPyL PET/CT. Eighty-one patients had evidence of PSMA-positive lymph node metastases, of whom 39 (48%) had no enlarged lymph nodes on CT; 18F-DCFPyL PET detected additional metastatic lymph nodes in 41/42 patients that had evidence of lymph node metastases on CT. 18F-DCFPyL PET altered patients' management in 17% of patients. CONCLUSION: 18F-DCFPyL PET/CT can be used as first-line imaging modality for therapy selection in patients with primary high-risk prostate cancer, without need for further diagnostic imaging procedures in the majority of patients.

Early lesion detection with 18F-DCFPyL PET/CT in 248 patients with biochemically recurrent prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (168Ga)-labelled radiotracers. Alternatively, fluorine-18 (18F)-labelled PSMA tracers are available, such as 18F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of 18F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value. METHODS: A total of 248 consecutive patients were evaluated and underwent scanning with 18F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq 18F-DCFPyL. RESULTS: In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected ('positive scan'). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39-50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy). CONCLUSION: 18F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for 68Ga-PSMA and 18F-PSMA-1007, with potentially increased detection efficacy compared to 68Ga-PSMA for patients with PSA <2.0.

Incidental extra-cardiac findings on 13N-ammonia myocardial perfusion PET/CT.

BACKGROUND: The objective of this study was to describe the prevalence of incidental extra-cardiac findings (IECFs) on myocardial perfusion PET/CTs and the prevalence of potentially clinically relevant and clinically irrelevant IECFs, as well as detection rate of previously unknown malignancies. METHODS AND RESULTS: From September 2013 until February 2016, a total of 1397 consecutive patients referred for the evaluation of possible ischemia by 13NH3 PET/CT were prospectively included in a database. IECFs were categorized into three groups: potentially clinically relevant IECFs, IECFs that could potentially cause chest pain, and clinically irrelevant IECFs. Additionally, the prevalence of previously unknown malignancies was determined. In 717 (51%) of these patients, 775 IECFs were reported and 115 IECFs were categorized as potentially clinically relevant in 109 (8%) patients. A total of 145 IECFs that could potentially cause chest pain were detected in 139 (10%) patients and 515 clinically irrelevant IECFs were detected in 469 (34%) of the patients. An unknown primary malignancy was histologically proven in 19 patients (1.4%). CONCLUSIONS: IECFs are detected on myocardial perfusion PET/CT in approximately half of the patients. In the present study, IECFs were potentially clinically relevant in 8% of the patients and in 1.4% an unknown malignancy was found, most of which were lung cancers.

Cardiac sympathetic activity in chronic heart failure: cardiac 123I-mIBG scintigraphy to improve patient selection for ICD implantation.

Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with 123I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients.

BACKGROUND: Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS). METHODS: For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS. RESULTS: MACE occurred in 23 patients (1.5 %): death (3, 0.2 %), myocardial infarction (4, 0.3 %) and late revascularisation (16, 1.3 %). Multivariate analysis showed an independent prognostic value of CCTA (p < 0.001), CACS of 100-400 (p = 0.035) and CACS of > 400 (p = 0.021). CCTA showed obstructive CAD in 3.1 % of patients with CACS = 0. No events occurred in patients with CACS = 0 without obstructive CAD at CCTA, whereas 2/23 patients (9 %) with CACS = 0 with obstructive CAD had a MACE. CONCLUSIONS: Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS = 0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.

Uptake of (18)F-fluoro-2-deoxyglucose in the Healthy Testes of Young Men as Assessed by Positron Emission Tomography/Computed Tomography; Including the Inter- and Intra-observer Variation.

Knowledge of the physiological testicular accumulation of (18)F-fluoro-2-deoxyglucose (FDG) is essential in order to discriminate between normal and pathological findings. In this study, the (18)F-FDG-uptake in healthy testes of young men was assessed using positron emission tomography/computed tomography (PET/CT)-scans. A total of 40 testes of 20 men with a mean age of 26.5 ± 3.9 years were evaluated. (18)F-FDG-uptake was expressed as the standardized uptake value (SUV). Testicular volume was measured on CT and PET. All scans were assessed by three researchers, one of whom assessed every scan twice. Laterality indices and inter- and intra-observer variation were evaluated. Correlation between the SUVmax and SUVpeak, between SUVmean and SUVpeak and between age and SUVpeak were assessed. Testes showed an average SUVmax of 3.42 ± 0.61, SUVpeak of 3.06 ± 0.54 and SUVmean of 2.44 ± 0.44. The average testicular volume on CT was 23.0 ± 6.4 ml, whereas on PET it was 18.0 ± 5.1 ml. Laterality indices were calculated of 0.077 ± 0.065 (SUVmax), 0.074 ± 0.066 (SUVpeak), 0.072 ± 0.063 (SUVmean), 0.245 ± 0.259 (CT), and 0.200 ± 0.188 (PET), respectively. Inter- and intra-observer reliability were found to be perfect for the SUVs (intraclass correlation coefficient [ICC] 0.992-1.0), but poor for testicular volumes (ICC 0.854-0.902). Testicular (18)F-FDG uptake in young men can be measured accurately on PET/CT and shows high symmetry. Consequently, (18)F-FDG PET/CT has the potential to become a useful instrument in the evaluation of the functioning of the individual testis.

No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats.

PURPOSE: [(123)I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [(123)I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [(123)I]FP-CIT. METHODS: Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [(123)I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [(123)I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [(123)I]FP-CIT binding to DATs. RESULTS: No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. CONCLUSION: We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [(123)I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of [(123)I]FP-CIT SPECT scans in routine clinical studies.