[111In-diethylene triamine penta-acetic acid-D-Phe1]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of 99mTc-EDDA/HYNIC-TOC were compared with those of 111In-DTPA-octreotide in six cases, and with those of 111In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of 111In-DTPA-octreotide but faster than that of 111In-DOTA-TOC, while urinary excretion was lower compared with the 111In derivatives. Semi-quantitative region of interest analysis showed that 99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the 111In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in 99mTc images. We conclude that 99mTcEDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available 111In-labelled octreotide derivatives.

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over ...

Iodized salt prophylaxis has been performed in Austria since 1963. Through this approach, mean urinary iodine excretion has been normalized to 144+/-23.5 microg/g creatinine per day. Thus Tyrol is no longer an endemic goiter area. We have analyzed the impact of iodized salt prophylaxis on thyroid cancer (TC) comparing data from the early 1960s with those corresponding to the period 1986 to 1995, when iodine supply was normalized. The study included 439 patients from Tyrol and Southern Tyrol. The incidence of TC in Tyrol has risen during the past decades from 3.07 between in 1957 and 1970 to 7.8 between 1990 and 1994 (CR/100000/year). We observed a rise in the percentage of differentiated adenocarcinomas (56% to 91.5%) with a predominance of papillary TC (54.4%) along with a decrease of anaplastic TC. In addition to these histological features, a shift to less advanced TNM stages, eg, T1-3, N0-1a, M0, was obvious, increasing from 29% to 72.2%, whereas advanced tumors, ie, T4 or N1b or M1, decreased from 71% to 28%. These changes have significantly improved prognosis. The current 5-year survival rate is 90.7% as compared with a rate of 73% in the 1960s; the values for 7-year survival are 89% and 48%, respectively. The marked effects of age, tumor stages, and histology on prognosis were confirmed with the Kaplan-Meier method. We conclude that together with normalization of iodine supply in an endemic goiter region the epidemiological profile of TC has changed. Even though the incidence of TC has risen, prognosis has significantly improved due to a shift towards differentiated forms of TC that are diagnosed at earlier stages.

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Background: Familial non-medullary thyroid cancer (fNMTC) is a complex genetic disorder that is more aggressive than its sporadic counterpart. Thus far, three genetic loci have been implicated in susceptibility to fNMTC by linkage analysis. Methods: We used linkage analysis to test the significance of two of the known susceptibility loci for fNMTC, TCO on 19p13 and NMTC1 on 2q21 in 10 fNMTC families, nine of which present with cell oxyphilia, a rare histological phenotype associated with TCO. Furthermore, we used two-locus linkage analysis to examine the possibility that the TCO and NMTC1 loci interact to increase the risk of NMTC. Results: The 10 families provided evidence for linkage at both TCO and NMTC, with LOD scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of NMTC, achieved a maximum LOD of 3.92, with an LOD of 4.51 when assuming 70% of families were linked, indicating that the segregation in these families is consistent with an interaction model. Most of this evidence came from a large Tyrolean family that singularly achieved a two-locus LOD of 3.21. Conclusions: These results provide further evidence that susceptibility genes for fNMTC exist at 19p13 and 2q21, and furthermore, raise the possibility that in a subset of fNMTC pedigrees, these loci interact resulting in significantly increased risk of NMTC for patients that carry both susceptibility loci.

Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n = 55) or pharmacological stress (n = 17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r = 0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r = 0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n = 23), these correlations were even better (r = 0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%-100% and 82%-98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.

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