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This article gives an overview of those small animal imaging studies which have been conducted on neurotransmitter function in the rat 6-hydoxydopamine (6-OHDA) model of Parkinson's disease, and discusses findings with respect to the outcome of clinical studies on Parkinsonian patients.

Aim: Ventricular arrhythmias have been shown to originate in the myocardial peri-infarct region due to irregular heterotopic conduction. Hypoperfused but viable myocardium is often localised in those areas and may be involved in the pathogenesis of arrhythmias. We tested the hypothesis that these myocardial perfusion/metabolism mismatches (MM) are significantly associated with ventricular arrhythmias in the chronic post infarction state., Patients, Methods: 47 post infarction patients were included in the study. 33 suffered from ventricular arrhythmia whereas 14 did not. All patients underwent (99m)Tc tetrofosmin SPECT and (18)F-FDG PET. A region-of-interest(ROI)-analysis was used to assess viable myocardium based on predefined MM-criteria. Univariate analyses as well as a logistic regression model for the multivariate analysis were carried out., Results: 94% of the arrhythmic patients displayed at least one MM-segment as compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed a statistically significant relation (p = 0.018). The logistic regression model predicted the occurrence or absence of arrhythmia in 85% of all cases. Multivariate analysis gave consistent results, after adjusting for symptomatic chronic heart failure (CHF), aneurysms and age., Conclusion: Our results support the hypothesis that hypoperfused but viable myocardium represents an arrhythmogenic substrate and is a relevant risk factor for developing ventricular arrhythmias following myocardial infarction. Therefore, the detection of MM-segments allows the identification of patients with a higher risk for future cardiac events.

Aim: The study presented here firstly compares the distribution of the binding potential of the serotonin-5HT2A receptor as measured in vivo with data of receptor density taken from literature. Secondly, the sensitivity of the method to detect gradual differences in receptor densities is evaluated., Methods: Positron emission tomography (PET) studies were carried out in 6 healthy volunteers using the selective serotonin-5HT2A ligand 18F-altanserin. The binding potential was quantified in 12 regions using Logan's graphical method and the equilibrium method. These data were compared to the distribution of receptor density as taken from literature., Results: The binding data in vivo correlated to autoradiography data (post mortem) with r = 0.83 (Pearson regression coefficient; p < 0.0001). A difference in the receptor density between two regions could be detected with p < 0.05 when it amounted at least to 18%., Conclusion: This study demonstrates a good agreement between in vivo data obtained with 18F-altanserin and PET in healthy volunteers and the true autoradiographically determined distribution of 5HT2A receptors in human brains. The in vivo method seems to be sensitive enough to detect changes in receptor density of more than 18%.

Aim: The characteristics of 5HT2 receptor binding were investigated in major depression in vivo using positron emission tomography and the radioligand F-18-altanserin., Methods: Twelve patients from families with high loading of depression living in a geographically restricted region were examined and compared with normal control subjects. At the time of the PET measurement all patients were remitted; in some of them remission was sustained by antidepressive medication. Binding potential was assessed by Logan's graphical analysis method., Results: The binding of F-18-altanserin was about 38% lower in patients than in healthy controls (p < 0.001). A multiple regression analysis revealed that this difference was mainly induced by depression rather than by medication., Conclusions: The data suggest that 5HT2 receptors are altered in depression. We present evidence for a reduction of the receptor density, which might be usable as trait marker of subjects susceptible for depressive illness.

The case of a 54 year old patient suffering from a prostatic carcinoma is presented. At the time of diagnosis multiple bone metastases were detected by bone scintigraphy. An initial improvement was observed following antiandrogenic therapy. After three years the patient presented with increasing bone pain, which was most prominent in the knee joints. A "superscan" was found in bone scintigraphy with an unusually high uptake in the peripheral skeleton. Bone marrow scinitgraphy showed a nearly complete metastatic displacement of central bone marrow and a peripheral marrow extension as explanation for the bone scan findings.

Human serum albumin millimicrospheres labeled with 99mTc-pertechnetate were used for evaluation of their mean retention time in the hepatic RES cells. For this purpose the retention function was derived from the liver time-activity curves by deconvolution analysis. Measurements in 50 patients with operated breast cancer revealed significantly shorter retention times in patients with extrahepatic metastases in comparison with patients without evidence of metastases or recurrences. Discriminant analysis of the retention times combined with other investigated parameters such as relative organ size and extraction fraction of the liver and spleen, age, weight and height of the patient, proved the method to be diagnostically valuable. In the examined group of patients metastases could be demonstrated with a sensitivity of 100% and a specificity of 92%.

The transfer function of the liver perfusion is an idealized time-activity curve that could be registered over the liver if a non-diffusible tracer would be injected directly into the abdominal aorta and no tracer recirculation would occur. The reproducibility of the transfer function was experimentally investigated in foxhounds. Both the routes of tracer application and the modes of data evaluation were varied and the perfusion was investigated under physiological and pathological conditions. The transfer function was calculated by deconvolution analysis of first-pass time-activity curves using the matrix regularization method. The transfer function showed clearly distinguishable arterial and portal-venous components. Repeated peripheral venous and central aortic applications resulted in reproducible curves. In addition to the arterial and portal-venous components the subcomponents of the portal-venous component could also be identified in the transfer function after ligation of the appropriate vessels. The accuracy of the mathematical procedure was tested by computer simulations. The simulation studies demonstrated also that the matrix regularization technique is suitable for deconvolution analysis of time-activity curves even when they are significantly contaminated by statistical noise. Calculation of the transfer function of liver perfusion and of its quantitative parameters seems thus to be a reliable method for non-invasive investigation of liver hemodynamics under physiological and pathological conditions.

A special 8-channel detector arrangement was used to determine atraumatically the mean blood flow velocities in the aorta and the large arteries of the lower extremities in man. Following intravenous injection of 99mTc-pertechnetate time-activity curves were recorded over defined measuring points over the arteries, from these the appearance times of the tracer determined, and the mean blood flow velocities calculated from the differences between appearance times (the minimal transit times) and the distances between measuring points. The simultaneous determination of the minimal transit times between the vena cava inferior and the root of the aorta, which correspond closely to the total cardiac transit times, permits recognition of cases in whom blood flow velocity is reduced as a result of cardiac disease.

99mTc-mercaptoacetyltriglycine (MAG3) has recently been introduced for imaging kidney function. Due to the much lower radiation dose per MBq, the total administered activity can be much higher than in the case of 131I-ortho-iodo-hippurate (OIH). The improved counting statistics make this tracer useful for parametric imaging of the kidneys. To investigate this potential of MAG3, its kinetics was compared with that of the reference tracer OIH in 38 patients. Parameters of extrarenal tracer kinetics such as the distribution volumes, the whole-body elimination times and the clearance rates showed a good correlation; however, the clearance rate of MAG3 was always lower than that of OIH. The intrarenal kinetics was investigated using the transfer function which was calculated by deconvolution analysis of the renographic curves. Parameters of the transfer function such as the amplitude, extraction fraction and mean transport time demonstrated a high correlation between the two tracers. Since MAG3 seems to be suitable for parametric imaging of kidney function, parametric images of perfusion, uptake, extraction and transport times were calculated by deconvolution analysis of the MAG3 pixel-renograms in various renal disorders. The parameters were distributed homogeneously throughout the parenchyma of normal kidneys. In a kidney with a hemodynamically significant renal artery stenosis the perfusion parameter was decreased and the time parameter was prolonged. Further examples of a renal graft acute tubular necrosis, an obstructive uropathy, an obstructive nephropathy and of a horse-shoe kidney demonstrate that the parametric images are useful for quantitative investigation of regional renal function.