Felix M. Mottaghy

Clinical relevance of imaging proliferative activity in lung nodules

PurposeRecently, the thymidine analogue 3′-deoxy-3′[18F]fluorothymidine (FLT) has been introduced for imaging proliferation with positron emission tomography (PET). In this prospective study, we examined the accuracy of FLT for differentiation of benign from malignant lung lesions and for tumour staging.MethodsA total of 47 patients with newly diagnosed pulmonary nodules on chest CT suspicious for malignancy were examined with FLT-PET in addition to routine staging procedures. A total of 43xa0patients also underwent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET imaging. Within 2 weeks, patients underwent resective surgery or core biopsy of the pulmonary lesion.ResultsHistopathology revealed malignant lung tumours in 32 patients (20 non-small cell lung cancer, 1 small cell lung cancer, 1 pulmonary carcinoid, 1 non-Hodgkin’s lymphoma, nine metastases from extrapulmonary tumours) and benign lesions in 15 patients. Increased FLT uptake was exclusively related to malignant tumours. FLT-PET was false negative in twoxa0patients with non-small cell lung cancer, in the patient with a pulmonary carcinoid and in threexa0patients with lung metastases. The sensitivity of FLT-PET for detection of lung cancer was 90%, the specificity 100% and the accuracy 94%. Fifteen out of 21 patients with lung cancer had mediastinal lymph node metastases. FLT-PET was true positive in 7/15xa0patients, resulting in a sensitivity of 53% for N-staging (specificity 100%, accuracy 67%). Clinical TNM stage was correctly identified in 67% (20/30) patients, compared to 85% (23/27) with FDG-PET.ConclusionFLT-PET has a high specificity for the detection of malignant lung tumours. Compared with FDG, FLT-PET is less accurate for N-staging in patients with lung cancer and for detection of lung metastases. FLT-PET therefore cannot be recommended for staging of lung cancer.

Dopaminergic dysfunction in attention deficit hyperactivity disorder (ADHD), differences between pharmacologically treated and never treated young adults : a 3,4-dihdroxy-6-[18F]fluorophenyl-l-alanine PET study

The dopaminergic system plays a key role in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate (MP), a dopamine (DA) reuptake inhibitor, is a drug of first choice for treating ADHD. This cross-over study investigated alterations in DA metabolism in young males with ADHD who had never been pharmacologically treated and MP-treated patients in comparison to healthy subjects. Dynamic 3,4-dihdroxy-6-[18F]fluorophenyl-L-alanine (FDOPA) PET scans were carried out on 20 male patients with ADHD and 18 healthy men. Eight ADHD patients had never been treated with psychostimulants, the rest had received MP. Based on the tissue-slope-intercept plot parametric images of FDOPA influx rate constant (Ki) were generated for each subject from dynamic 3D FDOPA datasets and transformed into standard stereotactic space. First a volume of interest analysis was performed on each single subject. In a second step data were introduced to a SPM2 analysis to detect significant changes in mean voxel Ki values between the normal control group and each patient group. In comparison to controls, ADHD patients as a group (irrespective of treatment status) showed a lower Ki in bilateral putamen, amygdala and dorsal midbrain. There was a lower Ki in the left putamen, right amygdala and right dorsal midbrain in untreated patients compared to controls together with a relative higher influx in the left amygdala and right anterior cingulate cortex. In contrast, methylphenidate treatment was associated with a significantly lower Ki in the striatum and amygdala bilaterally, and in the right dorsal midbrain. Untreated young adult ADHD patients showed a dopamine dysfunction that might be partly due to compensatory mechanisms. MP seems to down-regulate dopamine turnover. This effect might be one component in the mechanism of action of this drug in ADHD treatment.

Learning related interactions among neuronal systems involved in memory processes

Functional neuroimaging techniques using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have provided new insights in our understanding of brain function from the molecular to the systems level. While subtraction strategy based data analyses have revealed the involvement of distributed brain regions in memory processes, covariance analysis based data analysis strategies allow functional interactions between brain regions of a neuronal network to be assessed. The focus of this chapter is to (1) establish the functional topography of episodic and working memory processes in young and old normal volunteers, (2) to assess functional interactions between modules of networks of brain regions by means of covariance based analyses and systems level modelling and (3) to relate neuroimaging data to the underpinning neural networks. Male normal young and old volunteers without neurological or psychiatric illness participated in neuroimaging studies (PET, fMRI) on working and episodic memory. Distributed brain areas are involved in memory processes (episodic and working memory) in young volunteers and show much of an overlap with respect to the network components. Systems level modelling analyses support the hypothesis of bihemispheric, asymmetric networks subserving memory processes and revealed both similarities in general and differences in the interactions between brain regions during episodic encoding and retrieval as well as working memory. Changes in memory function with ageing are evident from studies in old volunteers activating more brain regions compared to young volunteers and revealing more and stronger influences of prefrontal regions. We finally discuss the way in which the systems level models based on PET and fMRI results have implications for the understanding of the underlying neural network functioning of the brain.

Primary progressive aphasia accompanied by environmental sound agnosia: A neuropsychological, MRI and PET study

As part of the frontotemporal dementias, primary progressive aphasia (PPA) is typically characterized by nonfluent speech with paraphasias, but there is growing evidence that also a fluent variant of PPA exists. We describe a patient suffering from PPA who adds to the broad clinical spectrum of this disorder. Moreover, we report for the first time that PPA may be associated with severe impairment in meaningful nonverbal sound recognition (environmental sound agnosia). These neuropsychological findings were found to be associated with distinct focal alterations in functional and structural neuroimaging.

Performance of Integrated FDG-PET/CT for Differentiating Benign and Malignant Lung Lesions - Results from a Large Prospective Clinical Trial

PurposeThe purpose of the study was to evaluate prospectively whether integrated 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) is more accurate for determination of malignancy in newly diagnosed pulmonary lesions compared to separate interpretation of CT and FDG-PET.ProceduresTwo hundred and seventy-six patients with newly diagnosed lung lesions underwent FDG-PET/CT. Helical CT, FDG-PET, and FDG-PET/CT were interpreted separately to determine the performance of each imaging modality. Histopathology served as reference in all patients, and in further 60 patients, a benign lesion was verified at follow-up (mean follow-up of 1,040xa0days).ResultsHistology revealed malignant lung tumors in 216 of 276 patients. With PET and PET/CT, a significantly lower number of lesions were classified as equivocal compared to CT alone (pu2009<u20090.001). Assuming that equivocal lesions are benign, performance of diagnostic tests was as follows: sensitivity, specificity, and accuracy for CT was 94, 75, and 90%, for PET 97, 83, and 94% (pu2009=u20090.021), and for PET/CT 96, 87, and 94% (pu2009=u20090.010). Assuming that equivocal lesions are malignant, sensitivity, specificity, and accuracy for CT was 99, 37, and 86%, for PET 99, 77, and 94% (pu2009<u20090.001), and for PET/CT 98, 68, and 92% (pu2009=u20090.002). PET and PET/CT showed the highest concordance (Ku2009=u20090.912; confidence interval 0.866–0.958). In lesions less than or equal to 3xa0cm, there was a significant difference in the performance of PET alone and multidetector row CT as well as PET/CT and multidetector row CT (pu2009=u20090.007), irrespective if equivocal findings were judged as malignant or benign.ConclusionFor differentiation of benign from malignant lung lesions, integrated FDG-PET/CT imaging was significantly more accurate than CT but not FDG-PET. The addition of metabolic imaging (FDG-PET) to morphological imaging (CT) leads to an increase in specificity and significantly reduced equivocal findings and is therefore recommended to further specify newly diagnosed lung lesions.

Intracoronary β-brachytherapy using a rhenium-188 filled balloon catheter in restenotic lesions of native coronary arteries and venous bypass grafts

PurposeWe have previously demonstrated the efficacy of intracoronary β-brachytherapy using a liquid 188Re-filled balloon in a randomised trial including de novo lesions. Percutaneous coronary interventions in restenotic lesions and in stenoses of venous bypass grafts are characterised by a high recurrence rate for restenosis and re-interventions. Against this background, we wanted to assess the impact of intracoronary β-brachytherapy using a liquid 188Re-filled balloon in restenotic lesions in native coronary arteries and venous bypass grafts.MethodsIn 243 patients, β-brachytherapy with 22.5xa0Gy was applied at a tissue depth of 0.5xa0mm. Patients were followed up angiographically after 6xa0months and clinically for 12xa0months. The primary clinical endpoint was the incidence of MACE (death, myocardial infarction, target vessel revascularisation). Secondary angiographic endpoints were late loss and binary restenosis rate in the total segment.ResultsAll irradiation procedures were successfully performed. A total of 222 lesions were in native coronary arteries; 21 were bypass lesions. Mean irradiation length was 41.6±17.3xa0mm (range 20–150xa0mm) in native coronary arteries and 48.1±33.9xa0mm (range 30–180xa0mm) in bypass lesions; the reference diameter was 2.57±0.52xa0mm and 2.83±0.76xa0mm, respectively. There was no vessel thrombosis during antiplatelet therapy. Angiographic/clinical follow-up rate was 84%/100%. MACE rate was 17.6% in the native coronary artery group and 38.1% in the CABG group (p<0.03). Binary restenosis rate was 22.5% and 55.6% (p<0.01), and late loss was 0.38±0.72xa0mm and 1.33±1.11xa0mm (p<0.001), respectively.ConclusionsWe conclude that intracoronary β-brachytherapy with a liquid 188Re-filled balloon using 22.5xa0Gy at a tissue depth of 0.5xa0mm in restenotic lesions is safe. It is associated with a low binary restenosis rate, resulting in a low occurrence rate of MACE within 12xa0months in restenotic lesions in native coronary arteries but not in vein grafts.

Improving binding potential analysis in [11C]raclopride PET studies using cluster analysis

To calculate binding potentials (BP) in [11C]raclopride brain PET studies a reference tissue model is widely used. The aim of the present study was to improve the determination of time activity curves (TAC) of reference tissue regions using cluster analysis. In four patients with Huntington disease TACs of a cerebellar reference region were calculated either from manually placed circular ROIs within the cerebellum or by cluster analysis. BP estimates derived from cluster analysis are independent from inter- and intraobserver variations and show an improved reproducibility combined with a low variability compared to manually placed cerebellar ROIs. This is of high value in longitudinal studies.

Relevant tumor sink effect in prostate cancer patients receiving Lu-177-PSMA-617 radioligand therapy

AIMnIn metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in 177Lu-PSMA-617 therapy was evaluated.nnnMETHODSnEleven consecutive prostate cancer patients receiving a first cylcle of 177Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The 68Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3.403 with different 68Ga-PSMA-11 thresholds based on the standardized uptake value (SUV).The kidney dose was estimated with the software ULMDOS using planar whole-body scintigrams.nnnRESULTSnKidney dose and SG uptake was inversely correlated to TTV, indicating high kidney dose and high SG uptake in case of low tumor load and low kidney dose and low SG uptake in case of high tumor load.nnnCONCLUSIONnOur data support the hypothesis that in 177Lu-PSMA-617 therapy an individualized treatment activity based on total tumor volume could be beneficiary.