Ventricular synchrony is not significantly determined by absolute myocardial perfusion in patients with chronic heart failure:A N-13-ammonia PET study

Background It is thought that heart failure (HF) patients may benefit from the evaluation of mechanical (dys)synchrony, and an independent inverse relationship between myocardial perfusion and ventricular synchrony has been suggested. We explore the relationship between quantitative myocardial perfusion and synchrony parameters when accounting for the presence and extent of fixed perfusion defects in patients with chronic HF. Methods We studied 98 patients with chronic HF who underwent rest and stress Nitrogen-13 ammonia PET. Multivariate analyses of covariance were performed to determine relevant predictors of synchrony (measured as bandwidth, standard deviation, and entropy). Results In our population, there were 43 (44%) women and 55 men with a mean age of 71 +/- 9.6 years. The SRS was the strongest independent predictor of mechanical synchrony variables (p <.01), among other considered predictors including: age, sex, body mass index, smoking, diabetes mellitus, dyslipidemia, hypertension, rest myocardial blood flow (MBF), and myocardial perfusion reserve (MPR). Results were similar when considering stress MBF instead of MPR. Conclusions The existence and extent of fixed perfusion defects, but not the quantitative PET myocardial perfusion parameters (sMBF and MPR), constitute a significant independent predictor of ventricular mechanical synchrony in patients with chronic HF

Impact of fasting on F-18-fluorocholine gastrointestinal uptake and detection of lymph node metastases in patients with prostate cancer

BACKGROUND: (18)F-fluorocholine PET/CT is used to detect lymph node metastases in prostate cancer patients. Physiological (18)F-fluorocholine in the gastrointestinal tract, especially in the intestines, may interfere with the detection of malignant lymph nodes. Fasting is frequently proposed in literature; however, scientific support is lacking. This study aims to determine the impact of fasting on (18)F-fluorocholine uptake in the gastrointestinal tract. METHODS: Eighty patients were studied, 40 fasted for at least 6 h prior to (18)F-fluorocholine administration while the other 40 did not fast. (18)F-fluorocholine uptake pattern and intensity were evaluated in the intestine near the abdominal aorta and four regions near the iliac arteries. (18)F-fluorocholine intensity was also measured in the liver, pancreas, stomach and spleen. FINDINGS: No statistically significant differences were found in (18)F-fluorocholine uptake in the gastrointestinal tract between the fasting and non-fasting group. CONCLUSIONS: Fasting for 6 h has no effect on (18)F-fluorocholine uptake in the gastrointestinal tract. Therefore, no effects on the detection of malignant lymph nodes are expected, and fasting is not recommended in our opinion

Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors

Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders. SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions. 6β-acetoxynortropane, a potent muscarinic M2 receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor. Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M2 receptor. 6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M1−3 receptors. The original 6β-acetoxynortropane displayed high affinity (Ki = 70–90 nM) to M2 receptors and showed good selectivity ratios to the M1 (65-fold ratio) and the M3 (70-fold ratio) receptors. All new derivatives showed reduced affinity to the M2 subtype and loss of subtype selectivity. It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M2 receptors

NEOnatal Central-venous Line Observational study on Thrombosis (NEOCLOT): Evaluation of a national guideline on management of neonatal catheter-related thrombosis

Background: In critically ill (preterm) neonates, central venous catheters (CVCs) are increasingly used for administration of medication or parenteral nutrition. A serious complication, however, is the development of catheter-related thrombosis (CVC-thrombosis), which may resolve by itself or cause severe complications. Due to lack of evidence, management of neonatal CVC-thrombosis varies among neonatal intensive care units (NICUs). In the Netherlands an expert-based national management guideline has been developed which is implemented in all 10 NICUs in 2014. Methods: The NEOCLOT study is a multicentre prospective observational cohort study, including 150 preterm and term infants (0-6 months) admitted to one of the 10 NICUs, developing CVC-thrombosis. Patient characteristics, thrombosis characteristics, risk factors, treatment strategies and outcome measures will be collected in a web-based database. Management of CVC-thrombosis will be performed as recommended in the protocol. Violations of the protocol will be noted. Primary outcome measures are a composite efficacy outcome consisting of death due to CVC-thrombosis and recurrent thrombosis, and a safety outcome consisting of the incidence of major bleedings during therapy. Secondary outcomes include individual components of primary efficacy outcome, clinically relevant non-major and minor bleedings and the frequency of risk factors, protocol variations, residual thrombosis and post thrombotic syndrome. Discussion: The NEOCLOT study will evaluate the efficacy and safety of the new, national, neonatal CVC-thrombosis guideline. Furthermore, risk factors as well as long-term consequences of CVC-thrombosis will be analysed

SPECT imaging of the dopaminergic system in (premotor) Parkinson's disease

In studies on (premotor) Parkinson's disease (PD), single photon emission computed tomography (SPECT) studies have focused on imaging of the presynaptic dopamine transporter (DAT) and postsynaptic dopamine D2 receptors (D2Rs). Here we review the results of SPECT studies on the dopaminergic system in PD, with particular emphasis on: the accuracy of SPECT imaging of the dopaminergic system to detect alternations of the dopaminergic system in early PD, the diagnostic accuracy of DAT SPECT in PD, the contribution of DAT imaging to detect preclinical phases of PD, and the potential role of SPECT imaging to monitoring progression of dopaminergic degeneration in P

(18)F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For Ga-68-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For (18)F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of (18)F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer.  Methods: Images were acquired 60 and 120 min after injection of (18)F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points.  Results: Our data showed a significantly increasing uptake of (18)F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P <0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-tonoise ratio of 11.93 was found for images acquired 120 min after injection (P <0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15).  Conclusion: (18)F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for (18)F-DCFPyL

In vitro and ex vivo storage phosphor imaging of short-living radioisotopes

Storage phosphor imaging may be of value for biodistribution studies of short-living radiotracers in small animals. Efficiency, sensitivity and resolution of imaging plates for short-living radioisotopes vary considerably but linear response to many radioisotopes was shown previously. However, these properties have not been compared directly for larger series of short-living radioisotopes, and only few studies have directly compared data obtained from phosphor images of tissue slices with results from dissection biodistribution studies. Therefore, we evaluated the properties of imaging plates for 11 short-living radioisotopes (18F, 32P, 67Ga, 89Sr, (99m)Tc, 90Y, 111In, 123I, 125I, 131I and 201Tl). We also evaluated the biodistribution of [123I]FP-CIT in rat brain using both the phosphor technique and conventional dissection methods. The imaging system showed a linear response for all tested radioisotopes over a wide range of radioactive concentrations and the efficiency, sensitivity and resolution varied greatly for the tested radioisotopes. Shielding experiments revealed the contribution of the various emission products of radioisotopes to these properties. However, quantitative biodistribution studies with radiotracers that are labeled with all tested radioisotopes, even 123I, are feasible. The results from the ex vivo biodistribution study, using [123I]FP-CIT as a radiotracer were similar for the phosphor imaging technique as compared to the dissection technique. Advantages of phosphor imaging in radiotracer distribution studies in rat brain as compared to dissection experiments may be more precise measurements, possibility to reanalyze imaging data and 3D-reconstruction. In conclusion, phosphor imaging is an attractive alternative for biodistribution studies of short-living radiotracers in small animal

Incidental Findings on 18 F-Fluorocholine PET/CT for Parathyroid Imaging

Introduction   18 F-choline positron emission tomography/computed tomography (PET/CT) is an upcoming imaging technique for the localization of hyperfunctioning parathyroid glands. However, 18 F-choline is a nonspecific tracer that also accumulates in malignancies, inflammatory lesions, and several other benign abnormalities. The aim of this study was to determine the occurrence and relevance of incidental findings on 18 F-choline PET/CT for parathyroid localization. Materials and Methods   18 F-choline PET/CTs performed in our center for parathyroid localization from 2015 to 2019 were reviewed. Abnormal uptake of 18 F-choline, with or without anatomical substrate on the co-registered low-dose CT and also incidental findings on CT without increased 18 F-choline uptake were recorded. Each finding was correlated with follow-up data from the electronic medical records. Results  A total of 388 18 F-choline PET/CTs were reviewed, with 247 incidental findings detected in 226 patients (58%): 82 18 F-choline positive findings with corresponding pathology on CT, 16 without CT substrate, and 149 18 F-choline negative abnormalities on CT. Malignant lesions were detected in 10/388 patients (2.6%). Of all 98 detected 18 F-choline positive lesions, 15 were malignant (15.3%), concerning 4 metastases and 11 primary malignancies: breast carcinoma ( n  = 7), lung carcinoma ( n  = 2), thyroid carcinoma ( n  = 1), and skin melanoma ( n  = 1). Conclusion  Clinically relevant incidental findings were observed in a substantial number of patients. In 15.3% of the incidental 18 F-choline positive findings, the lesions were malignant. These data contribute to better knowledge of 18 F-choline distribution, enhance interpretation of 18 F-choline PET/CT, and guide follow-up of incidental findings. Attention should especially be paid to breast lesions in this particular patient group with hyperparathyroidism in which women are typically over-represented

(18)F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes:Detection Rate, Image Quality, Activity Kinetics, and Biodistribution

There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For Ga-68-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For (18)F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of (18)F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer.  Methods: Images were acquired 60 and 120 min after injection of (18)F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points.  Results: Our data showed a significantly increasing uptake of (18)F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P <0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-tonoise ratio of 11.93 was found for images acquired 120 min after injection (P <0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15).  Conclusion: (18)F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for (18)F-DCFPyL

PET and SPECT imaging of the central dopamine system in humans

The neurotransmitter dopamine plays a role in many different functions of the human brain, ranging from psychomotor planning to cognition. This short review addresses which parts of the dopamine system can be imaged quantitatively in the living human brain using positron-emission tomography (PET) or single-photon emission computed tomography (SPECT). Nowadays, imaging of the nigrostriatal dopaminergic pathway in humans can be performed quantitatively using radiotracers like the aromatic amino acid decarboxylase (AADC) substrate [18F]FDOPA, vesicular monoamine transporter 2 (VMAT-2) radioligands derived from tetrabenazine or PET/SPECT radioligands that bind to the dopamine transporter (DAT). Using PET, also several other dopaminergic projection pathways (e.g. mesocortical projections) can be assessed in humans. Several antagonist PET radioligands for the dopamine D1 receptor have been developed successfully. In addition, well-validated antagonist PET and SPECT radioligands are available for imaging of dopamine D2/3 receptors in the living human brain. Recently, also agonist PET radioligands for the dopamine D2/3 receptors have become available, which afford the opportunity to evaluate the existence of the high-affinity state of these receptors in vivo. These agonist radiopharmaceuticals may also prove more sensitive to changes in dopamine concentrations (e.g. induced by the dopamine releaser amphetamine). Finally, selective antagonist PET radioligands for the dopamine D4 receptor have recently been synthesized and evaluated successfully in small laboratory animals, although these radioligands have not yet been reported as applied in human subjects. In conclusion, after almost three decades of research, several relevant parts of the central dopamine system can be assessed quantitatively in the living human brain using PET or SPECT. Future studies may include application of agonist radioligands and more dopamine receptor subtype selective radioligands