Alexius Joe

Diagnostic Performance of Whole Body Dual Modality 18F-FDG PET/CT Imaging for N- and M-Staging of Malignant Melanoma: Experience With 250 Consecutive Patients

Purpose To assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) for N- and M-staging of cutaneous melanoma. Patients and Methods This is a retrospective and blinded study of 250 consecutive patients (105 women, 145 men; age 58 ± 16 years) who underwent FDG-PET/CT for staging of cutaneous melanoma at different time points in the course of disease. Whole-body FDG-PET/CT was performed 101 ± 21 minutes postinjection of 371 ± 41 MBq FDG. Diagnostic accuracy for N- and M-staging was determined for CT alone, PET alone, and PET/CT. Results PET/CT detected significantly more visceral and nonvisceral metastases than PET alone and CT alone (98.7%, 88.8%, and 69.7%, respectively). PET/CT imaging thus provided significantly more accurate interpretations regarding overall N- and M-staging than PET alone and CT alone. Overall N- and M-stage was correctly determined by PET/CT in 243 of 250 patients (97.2%; 95% CI, 95.2% to 99.4%) compared with 2...

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment

Objective: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. Method: [18F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. Results: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. Conclusion: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Repeated Bone-Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial With the New, High-Energy Radiopharmaceutical Rhenium-188 Hydroxyethylidenediphosphonate

PURPOSE We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments. PATIENTS AND METHODS Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death. RESULTS In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043). CONCLUSION Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up.

PurposeThe role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy.MethodsAn FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up.ResultsSix of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3–13.7).ConclusionPCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: An exploratory approach

Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with (99m)Tc-hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.

The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

Introduction 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users. Methods Brain glucose metabolism in rest was assessed using 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. 18FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. Results As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. Conclusions Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction.

Nasolacrimal drainage obstruction after radioiodine therapy: case report and a review of the literature.

The authors report a 54-year-old woman with papillary thyroid carcinoma (Lindsay type, pT2 N0 M1) with pulmonary metastases. After a total thyroidectomy, a series of 3 radioiodine therapies were performed with a cumulative dose of 700 mCi I-131. After termination of the therapy, the patient was initially without complaints, but approximately 6 months later, epiphora was noted, first only of the right eye and eventually of both eyes. A whole-body I-131 scan performed 1 year after final radioiodine therapy showed atypical tracer accumulation in both medial orbital regions. This finding was new compared with the scan that was done 1 year before. Dacryocystography revealed bilateral occlusion of the lacrimal drainage system. A review of the literature shows that epiphora and lacrimal duct alterations are rarely investigated and potentially underestimated side effects after high-dose radioiodine therapy.

Feasibility of 2–deoxy–2–[18F]fluoro–D–glucose– A85380–PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo

SummaryNicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (α4β2) nicotinic acetylcholine receptor PET ligand (2–deoxy–2– [18F]fluoro–D–glucose–A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinsons disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2–deoxy–2–[18F]fluoro–D–glucose–A85380 PET–imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2–deoxy–2– [18F]fluoro–D–glucose–A85380 whole body PET–scans were performed on a Siemens PET/CT biographTM 75.4 min±6.7 after i.v. injection of 371.2±58.1 MBq. Average count rate density of left ventricle ROIs and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart–to–lung ratios were calculated in each volunteer and patient.Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart–to–lung ratios in the volunteer group were not different from patients suffering from Parkinsons disease or MSA (3.2 ± 0.5 vs 3.2 ± 0.8 and 2.96±0.7, mean ± SD), respectively.Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2–deoxy–2– [18F]fluoro–D–glucose–A85380 PET scans both in cardiac–healthy subjects and patients suffering from Parkinsons disease or multiple system atrophy. The heart– as well as the lung–tracer uptake was almost constant throughout all subjects leading to a good targetto– background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors.

Subclinical hyperthyroidism seems not to have a significant impact on systemic anticoagulation in patients with coumarin therapy

There is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n = 178; overt hyperthyroidism: n = 15; euthyroidism: n = 40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR <2.0 or >3.0). Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values <2.0. In patients with subclinical hyperthyroidism, therapy with antibiotics was predictive of INR-values >3.0, whereas therapy with thyroid suppressive drugs or TSH-values <0.1 mU/l was associated with INR-values <2.0. Moreover, in a subgroup of 40 patients with the positive history of both subclinical hyperthyroidism and euthyroidism intraindividual comparison with regard to the possible impact on anticoagulation therapy was performed which failed to show any significant differences in INR-values between the two thyroid metabolic conditions. In conclusion, subclinical hyperthyroidism seems to have no significant impact on coagulation metabolism in patients receiving anticoagulation therapy.