Helmut Höffken

Prospective study of presynaptic dopaminergic imaging in patients with mild parkinsonism and tremor disorders: Part 1. Baseline and 3-month observations

To record prospectively, from early presentation, the clinical features of parkinsonism and tremor disorders, in relation to evidence of dopaminergic deficit shown with [123I]‐FP‐CIT (DaTSCAN, Amersham Health) single photon emission computerised tomography (SPECT). Clinical signs were recorded in 62 patients, of whom 24 failed standard Parkinsons disease (PD) and essential tremor criteria, and 38 fulfilled UK Brain Bank step 1 PD criteria. Striatal radioligand uptake was graded visually as normal or abnormal, and specific:nonspecific ratios were calculated. Bradykinesia and rigidity showed significant overall association with abnormal scans (P ≤ 0.003), but rest tremor did not (P = NS). In the 24 patients not fulfilling specific criteria (mean age 63 [SD 9] years, disease duration 3 [SD 4] years), 10 (42%) had abnormal visual SPECT assessment and 14 (58%) had normal scans. Of 38 patients with early PD by clinical criteria (mean age 60 [SD 9] years, disease duration 3 [SD 1.7] years), 33 (87%) were visually abnormal. Baseline clinical diagnosis corresponded with SPECT imaging results in 51 of 62 cases (82%), which increased to 56 of 62 cases (90%) with amendment of seven clinical diagnoses at 3 months (blind to SPECT results). Akinetic–rigid cardinal diagnostic features of parkinsonism associate well with dopaminergic deficit in patients with early and mild clinical features. When these clinical features are uncertain, or the patient fails clinical diagnostic criteria, testing for dopaminergic deficit with [123I]‐FP‐CIT SPECT may assist the diagnostic process.

Clinical Value of Parathyroid Scintigraphy with Technetium-99m Methoxyisobutylisonitrile: Discrepancies in Clinical Data and a Systematic Metaanalysis of the Literature

There is a considerable discrepancy in the literature concerning the sensitivity of parathyroid scintigraphy (PS) with 99mTc-MIBI. We therefore analyzed our own data and compared them to the literature in a metaanalysis. All patients who received 99mTc -MIBI scintigraphy and subsequent surgery in our department for the detection of enlarged parathyroid glands in primary (pHPT) or secondary (sHPT) hyperparathyroidism between 1991 and 1999 were included in our retrospective analysis. The results of surgery served as the gold standard. For a true positive result, the scintigraphy had to predict the exact location of parathyroid adenoma (PA) or parathyroid hyperplasia (PH). We then compared these data to the results of a nonstatistical systematic metaanalysis of the literature. Patients (178) underwent PS between 1991 and 1999; 139 were operated on and included in this study. Of these, 109 had pHPT and 30 had sHPT. The sensitivity and specificity of the PS were found to be 45% / 94% for pHPT and 39% / 40% for sHPT. Fifty-two studies concerning PS were included in the metaanalysis. Sensitivities reported varied from 39% to > 90%. Consideration of the different possible techniques used for PS could not explain these discrepancies. Our data show that the sensitivity of PS in clinical routine may be lower than expected from the literature. Our data are consistent with other studies and with partially unpublished clinical observations from other university hospitals. We believe that a well-designed and properly conducted prospective study is necessary to evaluate the reasons for the differences observed.

18F-FDG PET, somatostatin receptor scintigraphy, and CT in metastatic medullary thyroid carcinoma: a clinical study and an analysis of the literature.

AimTo determine the clinical potential of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in patients with medullary thyroid carcinoma (MTC), we compared it to computed tomography (CT), and somatostatin receptor scintigraphy (SRS). Patients and methodsBlinded evaluation of PET, CT and SRS images obtained from 26 patients with histologically proven metastatic MTC was done by nuclear medicine and radiology specialists. Sites of tumour involvement were classified as ‘sure’ or ‘suspicious’. The data were analysed in comparison to two different standards. Either those sites classified as ‘sure’ by at least one of the methods were defined as the standard or those sites of involvement which were classified as ‘sure’ by at least two methods. ResultsDependent on the type of data analysis performed, PET was able to demonstrate 56.8%/80.6% of the tumour sites, CT showed 64.5%/79.6%, and SRS showed 47.5%/69.9% of the tumour sites. ConclusionOverall, CT is similar or better than PET in our patients (dependent on the standard) while SRS is inferior to both other techniques. Our data are in agreement with publications that consider CT superior to PET in the diagnosis of metastatic MTC while other studies show superiority of PET. However, a combination of CT and PET seems to be the most appropriate non-invasive diagnostic approach in patients with MTC.

Quantitative [123I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease

Abstract Single photon emission computed tomography (SPECT) using [123I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinsons disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [123I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [123I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra. To assess this question experimentally, we studied two different mouse models of PD, namely a mild 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication paradigm, to model mild nigrostriatal damage and the intrastriatal 6-hydroxydopamine paradigm to model more advanced nigrostriatal damage. Our data demonstrate that the striatal [123I]FP-CIT binding measured by SPECT in vivo precisely predicts the striatal dopamine concentrations, but does not necessarily correlate with the nigral dopaminergic cell number. Thus, the present work underscores that FP-CIT SPECT does only allow judging the integrity of the striatal dopaminergic nerve terminals, but not the nigral dopaminergic cells in PD. This finding may have significant impact on the use of [123I]FP-CIT SPECT as a surrogate marker for clinical trials aimed at measuring neuroprotection.

LeukoScan for imaging infection in different clinical settings: a retrospective evaluation and extended review of the literature.

Purpose The aim of the current study was to determine the overall diagnostic accuracy of Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan) for the routine detection of bone and soft tissue infections in a retrospective evaluation. Patients and Methods 138 patients (63 men, 75 women; mean age, 58.29 ± 25.38 years) with fever of unknown origin and possible endocarditis (n = 59), infection of arthroplastic joints (n = 20), arthritis (n = 16), peripheral (n = 15) and central bone infections (n = 14), soft tissue infection (n = 6), appendicitis (n = 4), pericarditis (n = 2), or vascular graft infection (n = 2) underwent imaging after injection of 555 to 925 MBq (15 to 25 mCi) Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments (LeukoScan). Results True-positive results were found in 63 of 81 lesions. The overall sensitivity and specificity were 76% and 84%, respectively. In arthritis, seven of seven foci could be detected, whereas false-negative results were found in infections of the femoral bone in three of nine lesions and in periprosthetic infections of long bones in three of eight lesions. Good results were found in five of six soft-tissue infections, in four of six patients with endocarditis, in three of four atypical cases of appendicitis, in two of two infected vascular grafts, and in one of one patient with pericarditis. Subacute and chronic infections of the spine always showed photopenic areas in eight of eight patients. If photopenic lesions were included as diagnostic criteria, the sensitivity and specificity were 88% and 67%, respectively. Conclusions Tc-99m–labeled antigranulocyte monoclonal antibody Fab’ fragments can be used for imaging acute infections of peripheral bones and soft tissues. False-negative results are likely in patients with chronic infections. Sensitivity can be increased while decreasing specificity by including photopenic lesions in the spine as diagnostic criteria for localizing disease.

Dopamine transporter imaging and SPECT in diagnostic work‐up of Parkinson's disease: A decision‐analytic approach

As a diagnostic test for patients with suspected Parkinsons disease (PD), single photon emission computed tomography (SPECT) using [123I]FP‐CIT tracer has better sensitivity but is more expensive than regular clinical examination (CE). Our objective was to evaluate the clinical and economic impacts of different diagnostic strategies involving [123I]FP‐CIT SPECT. We developed a decision tree model to predict adequate treatment‐month equivalents (ATME), costs, and incremental cost–effectiveness ratio (ICER) during a 12‐month time horizon in patients with suspected PD referred to a specialized movement disorder outpatient clinic. In our cost– effectiveness analysis, we adopted the perspective of the German health care system and used data from a German prospective health care utilization study (n = 142) and published diagnostic studies. Compared strategies were CE only (EXAM+), SPECT only (SPECT+), SPECT following negative CE (SINGLE+), and SPECT following positive CE (DOUBLE+). Costs of SPECT amounted to €789 per investigation. Based on our model, expected costs (and ATME) were €946 (52.85 ATME) for EXAM+, €1352 (53.40 ATME) for DOUBLE+, €1731 (32.82 ATME) for SINGLE+, and €2003 (32.96 ATME) for SPECT+; performance of SPECT was induced in 0%, 54%, 56%, and 100% of the patients, respectively. DOUBLE+ was more effective and less expensive than SINGLE+ or SPECT+; thus these two do not offer reasonable choices. The ICER of DOUBLE+ compared to EXAM+ was €733 per ATME gained. In sensitivity analyses, the ICER of DOUBLE+ versus EXAM+ ranged from €63 to €2411 per ATME gained. Whether the diagnostic work‐up of patients referred to a specialized movement disorder clinic with a high prevalence of PD should include [123I]FP‐CIT SPECT depends on patient preferences and the decision makers willingness to pay for adequate early treatment. SPECT should be used as a confirmatory test before treatment initiation and limited to patients with a positive test result in the clinical examination. These results should be adjusted to the specific setting and individual patient preferences.

Influence of somatostatin receptor scintigraphy and CT/MRI on the clinical management of patients with gastrointestinal neuroendocrine tumors: an analysis in 188 patients.

Aim: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. Patients and Methods: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). Results: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1–3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. Conclusion: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT.

Assessment of ventricular function with first-pass radionuclide angiography using technetium 99m hexakis-2-methoxyisobutylisonitrile: a European multicentre study.

In the context of a multicentre study on the use of technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi), we evaluated the accuracy of the ventricular function assessed at rest by means of first-pass radionuclide angiocardiography acquired during the injection of the tracer for myocardial perfusion scintigraphy. The results were compared with first-pass studies performed using reference tracers sodium pertechnetate Tc 99m or technetium 99m diethylene triamine penta-acetic acid or with gated radionuclide angiocardiography. A total of 66 patients of the 105 enrolled in the study could be evaluated. The comparison of the first-pass studies was possible in 33 subjects with regard to the left ventricular ejection fraction, yieldingr=0.909 (P< 10−6), and in 22 cases with regard to the right ventricular ejection fraction, yieldingr=0.712 (P<0.001). The comparison between the first-pass study using99mTc-Sestamibi and the equilibrium gated radionuclide angiocardiography was possible for the left ventricular ejection fraction in 26 cases, withr=0.937 (P<10−6), and for the right ventricular ejection fraction in 15 subjects, withr=0.783 (P<0.001). In conclusion, the assessment of ventricular function performed by acquiring a first-pass radionuclide angiocardiograph during the injection of99mTc-Sestamibi for perfusion myocardial scintigraphy can be considered reliable and accurate, when compared with the usually employed techniques. This result confirms the feasibility of a combined evaluation of perfusion and function at rest and during stress testing, which represents one of the most interesting advantages offered by the use of99mTc-Sestamibi.

Incidental Non-Secreting Adrenal Masses in Cancer Patients: Intra-Individual Comparison of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography with Computed Tomography and Shift Magnetic Resonance Imaging

The ability of integrated 18F-fluoro-deoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUVmax), liver SUVmax and tumour/liver SUVmax ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUVmax ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUVmax or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 − 97%) was similar to that for FDG PET/CT (94 − 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUVmax ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

Unexpected 99mTc-tetrofosmin findings during myocardial perfusion scintigraphy: intraindividual comparison with PET/computed tomography.

Objective99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during 99mTc-tetrofosmin myocardial perfusion scintigraphy (MPS). Materials and methodsWe investigated 2155 patients with 99mTc-tetrofosmin MPS during 2006–2007. One thousand four hundred and eighty-six of these patients had no coronary history and were sent to our department due to newly developed thoracic complaint such as chest pain, dyspnea and others. Six hundred and sixty-nine patients had coronary history. All patients underwent 99mTc-tetrofosmin exercise study. Patients with unexpected extracardiac 99mTc-tetrofosmin findings during MPS were referred to PET/CT for further diagnostic investigation. Region of interest (ROI; 99mTc-tetrofosmin) and SUVmax (2-[18F]fluoro-2-deoxy-D-glucose, 18F-FDG) were estimated and the results were compared with histological findings. ResultsAbnormal mediastinal and/or thoracic activities were visualized in six of the 2155 patients with 99mTc-tetrofosmin images. Subsequently, the patients underwent resection of a thymoma (n=2), nonsmall cell lung cancer (n=1) and breast cancer (n=3). In the patients with breast cancer one was a male patient with ductal, invasive breast cancer. Benign thymomas showed high 99mTc-tetrofosmin ROI >4.0 and low 18F-FDG SUVmax <2.0, whereas low 99mTc-tetrofosmin ROI <2.0 were found in nonsmall cell lung cancer and breast cancer and high 18F-FDG SUVmax >2.5 in these malignant tumors. ConclusionDuring 99mTc-tetrofosmin SPECT exercise stress tests performed in patients with suspected coronary artery disease, much more attention must be given to unexpected extracardiac uptakes. With 99mTc-tetrofosmin a large variety of different unknown tumors can be detected during MPS.