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Since, to date very limited information on the distribution and function of the adenosine A3receptor is available, the development of suitable radioligands is needed. Recently, we introduced [ 18F]FE@SUPPY (5-(2-[ 18F]fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate) as the first PET-ligand for the A3R. Regarding the metabolic profile – this class of dialkylpyridines comprises two ester functions within one molecule, one carboxylic and one thiocarboxylic – one could expect carboxylesterases significantly contributing to cleavage and degradation. Therefore, our aim was the development of [ 18F]FE@SUPPY:2 (5-ethyl 2,4-diethyl-3-((2-[ 18F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate), the functional isomer containing the label at the thiocarboxylic moiety.

Escitalopram the S-enantiomer of the racemate citalopram, is clinically more effective than citalopram in the treatment of major depressive disorder. However, the precise mechanism by which escitalopram achieves superiority over citalopram is yet to be determined. It has been hypothesized that the therapeutically inactive R-enantiomer competes with the serotonin-enhancing S-enantiomer at a low-affinity allosteric site on serotonin reuptake transporters (SERTs), and reduces the effectiveness of the S-enantiomer at the primary, high-affinity serotonin-binding site. This study summarizes the results of two recent single-photon emission computerized tomography studies measuring SERT occupancy in citalopram-treated and escitalopram-treated healthy volunteers, after a single dose and multiple doses (i.e. under steady-state conditions). The single-dose study showed no attenuating effect of R-citalopram. After multiple dosing, however, SERT occupancy was significantly reduced in the presence of R-citalopram. Under steady-state conditions, R-enantiomer concentrations were greater than for the S-enantiomer because of slower clearance of R-citalopram. A pooled analysis suggests that build-up of the R-enantiomer after repeated citalopram dosing may lead to increased inhibition of S-enantiomer occupancy of SERT. This review adds to the growing body of evidence regarding differences in the dynamics of SERT occupancy, that is, molecular mechanisms underlying the often-observed superior clinical efficacy of escitalopram compared with citalopram in major depressive disorder.

SummarySince to date very limited information on the distribution and function of the adenosine A3receptor is available, the development of a suitable radioligand is needed. Such a selective radioligand can then be used for quantitative autoradiography, preclinical studies in animals and subsequent human PET applications. Recently, a promising candidate compound, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY), has been presented. The successful preparation of a suitable labelling precursor and the evaluation and optimization of the radiosynthesis of [18F] FE@SUPPY is presented herewith.For satisfactory yields, a reaction temperature of 75 °C has to be applied for at least 20 min using 8–10 mg of precursor. Until now, 15 complete high-scale radiosyntheses were performed. Starting from an average of 51±12 GBq (average ±SD; range: 30–67 GBq) [18F]fluoride, 9.4–3.6 GBq of formulated [18F]FE@SUPPY (32.3±12.4%, based on [18F]fluoride, corrected for decay) were prepared in <105 min.

So far, [carbonyl-11C]WAY-100635 is the PET-tracer of choice for 5HT1A-receptor-imaging. Since the preparation is still a challenge, we aimed at (1) the evaluation of various essential parameters for the successful preparation, (2) the simplification of the radiosynthesis and (3) the establishment of a safe and fully automated system. The preparation is based on a commercial synthesizer and all chemicals are used without further processing. We found a low failure rate (7.7%), high average yield (4.0 ± 1.0 GBq) and a specific radioactivity of 292 ± 168 GBq/μmol (both at the end of synthesis, EOS).

PET imaging of the μ-opioid receptor (OR) is still restricted to [11C]carfentanil ([11C]CFN) but its use is limited due to its short half-life and high agonistic potency. Recently, the radiosynthesis of [18F]fluoroalkyl esters of CFN was proposed, unfortunately yielding products not suitable for human PET due to their low specific activities. Therefore, our rationale was to develop a reliable radiosynthesis of a [18F]fluoroethylated CFN derivative overcoming these drawbacks.

Bei der Aufrüstung einer Gammakamera von einem 5/8″ auf einen 1″ dicken Kristall mit StarBrite-Technologie wurden die Veränderungen der Abbildungseigenschaften für planare Szintigraphie, SPECT und für PET im Koinzidenzmodus untersucht. Für planare und SPECT-Parameter wurden die Leistungsparameter gemäß dem NEMA-Standard-Protokoll NU1-2001 gemessen. Für die Werte der inneren Uniformität, der inhärenten Ortsauflösung, der Linearität, der Energieauflösung, der räumlichen Systemauflösung und der tomographischen Systemauflösung ergaben sich keine systematischen Unterschiede. Lediglich die Systemempfindlichkeit nahm für den dickeren Kristall signifikant zu. Die Bildqualität der Kamera als PET-Scanner im Koinzidenzmodus wurde gemäß NEMA NU2-2001 bestimmt und ergab eine wesentliche Steigerung des Bildkontrastes. Für den klinischen Einsatz relevante Veränderungen der Bildqualität wurden durch die visuelle Beurteilung planarer Szintigramme von Patienten bestimmt, die an zwei Gammakameras gleichen Typs mit 5/8″-Kristall und unmittelbar danach mit dem 1″-Kristall aufgenommen wurden. Auch bei diesem klinischen Vergleich wurde kein statistisch signifikanter Unterschied gefunden.

ABSTRACTThe biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [18F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [18F]ciprofloxacin to select target tissues. Healthy volunteers (n= 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 ± 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [18F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [18F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t1/2s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t1/2, >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 ± 1.0 and 9.9 ± 4.4, respectively). The brain radioactivity concentrations were very low (<1 kBq · g−1) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated.

The influence of thyroid hormones on the immune system is controversial. We analyzed the cytokine expression pattern of T lymphocytes in patients with severe nonimmune hypothyroidism in order to establish the role of thyroid hormones on the immune system. The study comprised 7 patients (1 male and 6 females) 20 to 76 years of age (mean age, 53 years), without signs of chronic thyroiditis, verified by histology and laboratory data. The patients were studied 5 weeks after total thyroidectomy. Peripheral blood mononuclear cell (PBMC) cultures and intracellular cytokine detection by flow cytometry before and after thyroid hormone replacement therapy were performed (free thyroxine [FT4] 0.030 ± 0.034 ng/dL, versus FT4: 2.16 ± 0.68 ng/dL). The control group consisted of 7 healthy subjects (FT4: 1.20 ± 0.21 ng/dL). We found no significant differences in the cytokine pattern (interferon [IFN]-γ, IL-2, interleukin [IL]-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor [TNF]-α, TNF-β) of CD4+and CD8+between the matched groups (hypothyroid subjects versus controls, levothyroxine treated subjects versus controls). Our data show no change in the type 1/type 2 balance of peripheral CD4+and CD8+T lymphocytes from patients with nonimmune hypothyroidism. According to our results, the hypothyreotic state does not contribute to the reported changes in cytokine production patterns in Hashimoto's thyroiditis.

An increased uptake of bone-seeking radiopharmaceuticals into malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. The tracers used in clinical routine for bone scanning are methylene-diphosphonate (MDP), dicarboxypropane-diphosphonate (DPD) and ethylenediaminetetramethylene-phosphonate (EDTMP). MDP and DPD are usually labelled with 99mTc for diagnostic use, whereas EDTMP is labelled with 153Sm for therapeutic purposes. This study aimed to compare, for the first time, bone scanning with an improved preparation of 99mTc-EDTMP (by the addition of rhenium) (carrier-added) with 99mTc-DPD. Twenty malignant bone lesions were investigated in 10 patients. The ratios of bone lesion to soft tissue (BLST) and of bone lesion to normal bone (BLNB) were compared 3 h after the injection of either compound. Quantitative analysis demonstrated a significant (P<0.05) difference in BLST ratio in favour of 99mTc-DPD. The BLNB ratio was not significantly different. Visual image analysis resulted in a clinically comparable interpretation of imaging studies with the use of 99mTc-DPD and carrier-added 99mTc-EDTMP. These preliminary data support the concept of carrier addition to increase bone uptake by the modification of the complex structure of 99mTc-EDTMP. However, any advantage over conventional 99mTc-based tracers for bone scintigraphy in clinical use needs to be demonstrated in controlled trials.

Aim:To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using 99mTc-MAG3 renography. Methods:27 consecutive thyroidectomized patients (7 males and 20 females) aged 19–79 (mean 53) years were included in the present study. 99mTc-MAG3 renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, 51Cr-EDTA clearance and serum creatinine concentrations were determined. Results:The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 ± 0.44 vs. 1.04 ± 0.32 mg/dl, p < 0.05). According to the 51Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 ± 18 vs. 75 ± 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for 99mTc-MAG3 before and after treatment (total excreted activity 20 min after administration 51 ± 12 vs. 54 ± 14%; Tmax left:right 4.2 ± 1.77 : 3.91 ± 1.06 min vs. 4.1 ± 1.66 : 4.4 ± 1.96 min). Conclusions:We did not find any influence of thyroid hormones on the outcome of 99m Tc-MAG3 renography. As 99mTc-MAG3 reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.

Recently, two fluorine-18 labelled derivatives of flumazenil were described: 5-(2'-[¹⁸F]fluoroethyl)-5-desmethylflumazenil (ethyl 8-fluoro-5-[¹⁸F]fluoroethyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylate; [¹⁸F]FEFMZ) and 3-(2'-[¹⁸F]fluoro)-flumazenil (2'-[¹⁸F]fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carbo- xylate; [¹⁸F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [¹⁸F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two-step procedure was developed: First, [¹⁸F]fluoride was reacted with 2-bromoethyl triflate using the kryptofix/acetonitrile method to yield 2-bromo-[¹⁸F]fluoroethane ([¹⁸F]BFE). In the second step, distilled [¹⁸F]BFE was reacted with the tetrabutylammonium salt of 3-desethylflumazenil (8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylic acid) to yield [¹⁸F]FFMZ. The synthesis of [¹⁸F]FFMZ allows for the production of up to 7 GBq of this PET-tracer, enough to serve several patients. [¹⁸F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd.

GoalsWhen thyroid and other cancers are "cured" it is often assumed that the patients are able to resume their normal lives. This was a cross-sectional study to evaluate health-related quality of life (HRQOL) and to identify rehabilitation needs of patients with non-metastatic thyroid cancer under thyroxine supplementation therapy.Patients and methodsIncluded in the study were 150 consecutive patients with differentiated thyroid cancer (age 52±14 years, range 25–83 years; male/female 39/111). All patients had a history of total thyroidectomy followed by radioiodine ablation, were free of metastatic disease and under levothyroxine treatment. The mean period since the diagnosis of thyroid cancer was 5.5±6 years (range 0–23 years). Health-related quality of life was evaluated using the SF-36 Health Survey. The findings were compared with sex- and age-matched reference values.Results"Role-emotional" and "Vitality" were significantly lower ( P<0.001 and P<0.005, respectively) in the group as a whole ( n=150). In the subgroup of patients with a recent (less than 1 year) diagnosis of thyroid cancer ( n=51), however, the following subscales were significantly lower: "Mental Health" ( P<0.01), "Role-emotional" ( P<0.001), "Role-physical" ( P<0.005), "Social functioning" ( P<0.005) and "Vitality" ( P<0.001). Multiple regression analysis identified a significant positive correlation between "Mental Health", "Physical functioning", "Vitality", "Role-emotional" and "Social functioning" with the time since initial diagnosis, and there was also a positive correlation between "Physical functioning", "Bodily pain" and "Role-emotional" with male gender.ConclusionsThese findings indicate that "Vitality", "Role-physical", "Mental Health", "Role-emotional" and "Social functioning" are significantly impaired during the first year after diagnosis. Thereafter, quality of life improves correlating with the time since initial diagnosis. However, "Vitality" and "Role-emotional" remain permanently impaired in thyroid cancer patients. A multidisciplinary rehabilitation concept should include psychological support and an early start to exercise to improve physical performance of these patients leading to better HRQOL and to help them fulfill their social role earlier.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for followup.

Anti–carcinoembryonic antigen radioimmunoscintigraphy (anti-CEA RIS) in colorectal adenocarcinoma has been reported to allow a better estimation of the local tumor extension than other radiologic methods. This study evaluated the clinical feasibility of a 99=Tc-labeled anti-CEA monoclonal antibody (BW 431/26, Behring Institute, FRG) in 11 patients for staging of primary adenocarcinoma of the lung. The primary tumor size ranged from 3 to 8 cm with a mean of 4 cm. Mediastinal and hilar nodes were present in four patients, intrapulmonary metastases were present in two patients, and pleural and liver metastases were present in one patient each. The CEA levels were in the range of 2 to 265 ng/ml and elevated (>5 ng/ml) in six patients. Planar scintigraphy was performed at 6 h and 24 h post injection (pi). Analog and digitized images were interpreted by two observers. One patient was imaged twice and experienced serum sickness due to human anti-mouse antibodies (HAMA) after the second study, which showed marked unspecific tracer uptake in liver, spleen, and bone marrow, but no specific uptake by the tumor and was excluded from further analysis. Visual interpretation identified the primary tumor clearly in seven patients. No tumor imaging was observed in two patients. Two patients were classified as having questionable imaging due to a poor separation of tumor uptake from mediastinal blool pool. The primary tumor could be clearly delineated in both patients after comparison with the chest radiograph. Thus, the overall sensitivity for imaging of the primary tumor was 82 percent. The average target/background ratio was 1.31 ± 0.17:1 at 6 h pi, and 1.30 ± 0.16:1 at 24 h pi. Hilar and mediastinal nodes were correctly suspected in three patients, but the cardiac blood pool hampered a clear interpretation. Intrapulmonary and pleural metastases were diagnosed in all cases. The single liver metastasis was missed because of the high unspecific tracer uptake. Planar anti-CEA RIS with 99mTc BW 431/26 was superior to computed tomography (CT) in one case with subtotal tumor resection. We summarize that at present, planar anti-CEA RIS with 99mTc BW 431/26 cannot be advised as a routine staging procedure in adenocarcinoma of the lung, but it may be helpful in the detection of residual or recurrent tumor tissue. (Chest 1991; 99:14–19)

The aim of the study was to evaluate if D-dimer and thrombin-antithrombin HI complex determinations in patients with clinically suspected pulmonary embolism create a discrimination between patients to be further investigated with lung scanning and those who should be investigated for other diseases mimicking pulmonary embolism. The Data-Fi Dimertest Latex Assay, MAbCO Diniertest EIA, and TAT EIA were performed in 100 consecutive patients (26 percent outpatients) who were sent to our institution for lung scanning by their attending physicians because of clinically suspected pulmonary embolism. The D-dimer Latex Assay was positive (>500 ng/ml) in 12 (48.0 percent) of 25 patients with high probability of pulmonary embolism and in one (11.1 percent) of nine with intermediate probability, respectively. Only one patient (1.5 percent) with a normal scan had a positive latex assay, presumably due to inapparent bleeding after a computed tomographic (CT)guided liver biopsy. Referring to 120 ng/ml as upper limit of normal (mean ±2 SD of healthy controls), the D-dimer enzyme immunoassay (EIA) was positive in 21 (84.0 percent) of 25 patients with high probability, in six (66.7 percent) of nine patients with intermediate probability, and in 40 (60.6 percent) of 66 patients with normal/low probability of pulmonary embolism, respectively. The TAT EIA was positive (> mean ±2 SD of healthy controls = 3.53 ng/ml) in 18 (72.0 percent) of 25 patients with high probability, in five (55.6 percent) of nine patients with intermediate probability and in 16 (24.2 percent) of 66 patients with normal/low probability of pulmonary embolism. A normal result in one of these hemostaseologic tests did not predict a low probability of pulmonary embolism after lung scanning. Thus, it is not justified to exclude patients with clinically suspected pulmonary embolism from further investigation by lung scanning because of a normal result in one of these tests.

The feasibility of using 123I-heptadecanoic acid (HDA) as a metabolic tracer was studied. Different administration routes of HDA were compared. An intracoronary bolus injection was given to calves (n=3), and an intravenous injection was given to patients (n=4). In addition, we examined the influence of 4-h halothane anesthesia in calves and in patients the impact of an insulin (1.5 IU/kg)+ glucose (1.5 g/kg) infusion on the myocardial kinetics of HDA. Data were accumulated with a scintillation probe in calves (t=50 min) and a gamma camera in patients (t=70 min). In calves after an intracoronary bolus injection of HDA the myocardial time-activity curve could be described by two exponentials. The mean elimination halftime of the initial phase (ta 1/2) was 7.3 min and that of the second phase (tb 1/2) was 35 min. The ratio of the size of the initial and second component at to was 0.93. Halothane anesthesia prolonged the elimination half-times and reduced the component ratio. The biphasic behavior of the myocardial time-activity curve was maintained in patients after intravenous administration of HDA under basal conditions (initial ta 1/2=8.4 min). However, during infusion of insulin+glucose the decline in the myocardial activity was prolonged and monoexponential. This data shows that insulin glucose, interfering with fatty acid metabolism, influences the myocardial washout of HDA, and thus support its use as a metabolic tracer.

A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 μg/ml; normal range 12.5–26.0 μg/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.

The purpose of this study was to determine whether the hepatic uptake of dialysed technetium-99m labelled low-density lipoprotein (99mTc-LDL) reflects the hepatic LDL receptor activity and to what extent the non-LDL receptor-dependent 99mTc-LDL uptake by non-parenchymal cells relates to the diagnostic utility of quantitative 99mTc-LDL scintigraphy of the liver. New Zealand White rabbits and Watanabe Heritable Hyperlipidaemic rabbits, which were sacrificed 24 h after simultaneous injection of 99mTc-LDL and iodine-125 labelled LDL, were clearly discriminated by their hepatic 99mTc-LDL uptake according to their genetically different hepatic LDL receptor activity. Yet the hepatic 99mTc-LDL uptake exceeded the 125I-LDL uptake in all animals. The different hepatic uptake of the tracers was elucidated in the isolated perfused rat liver and was due to rapid intracellular degradation and the release of low molecular catabolites of 125I-LDL. In contrast, 99mTc activity was trapped in the liver. Analysis of biliary 99mTc activity provided evidence for the excretion of 99mTc-labelled apolipoprotein B. The amount of biliary excreted protein-bound 99mTc was linked to total hepatic 99mTc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion. Collagenase liver perfusion in Sprague-Dawley rats 90 min following simultaneous injection of 99mTc- and 125I-LDL and subsequent cell separation by gradient centrifugation revealed that 99mTc-LDL and 125I-LDL had a comparably low uptake into non-parenchymal cells; thus its contribution can be neglected for scintigraphic purposes. Planar scintigraphy was performed in New Zealand White and Watanabe Heritable Hyperlipidaemic rabbits. The different hepatic LDL receptor activities of the two groups were reflected by the slope of the liver/heart ratios over 24 h post injection and correlated well with their respective cumulative hepatic 99mTc-LDL uptake. Thus, we have been able to show that 99mTc-LDL scintigraphy using dialysed 99mTc-LDL can quantitate different genetically determined hepatic LDL receptor activities. The finding of the biliary excretion of 99mTc-labelled apolipoprotein B deserves further attention for its possible diagnostic utility.

The goal of the present study was to optimize technetium-99m labelling of low-density lipoprotein (LDL) and to investigate the in vitro and in vivo properties of the tracer to determine whether its application for quantitative scintigraphy of hepatic LDL receptor activity is feasible. LDL labelled with iodine-125 by the iodine monochloride method was used as a reference tracer. Comparison of different assessments of radiochemical purity [trichloro-acetic acid precipitation (%ppTCA), paper chromatography, size-exclusion chromatography and chloroform-methanol extraction] exhibited %ppTCA to be superior as a parameter of tracer quality. In spite of a high radiochemical purity immediately after labelling, modifications of 99mTc labelling of LDL did not overcome the poor long-term stability of the tracer. Subsequent dialysis in phosphate buffer over about 3 h sufficiently increased the long-term stability in vitro and in vivo. The competitive recognition of dialysed 99mTc-LDL and 125I-LDL with native LDL by high-affinity binding sites was demonstrated in human hepatoma cells (HepG2) and human fibroblasts. Biodistribution data of simultaneously injected 99mTc-LDL and 125I-LDL in New Zealand White rabbits showed a high uptake of both tracers in tissues with high LDL receptor activity, yet 99mTc-LDL uptake exceeded 125I-LDL uptake by two- to sevenfold. In contrast to 125I-LDL, 99mTc-LDL showed a higher unspecific uptake into the bone marrow and the spleen, suggesting an additional uptake mechanism probably via the scavenger pathway. Curve deconvolution of plasma clearance in five female New Zealand White rabbits and five male hyperlipidaemic patients again showed a marginally different biokinetic behaviour of 99mTc-LDL and 125I-LDL. It is concluded that dialysis of 99mTc-LDL substantially increases long-term stability, which is essential for quantification purposes, and that the dialysed tracer has retained its biological integrity as it is recognized by the LDL receptor in vitro. It remains to be determined to what extent the estimation of hepatic LDL receptor activity by quantitative 99mTc-LDL scintigraphy is influenced by the different biokinetic behaviour of 99mTc-LDL and 125I-LDL.

Interferon-γ (IFN-γ) and tumor necrosis factor (TNF) are lymphokines with a potent hematopoietic progenitor cell suppressive capacity. In untreated and immunosuppressed patients with severe aplastic anemia (SAA) and in control individuals we measured (a)serum levels of IFN- γ and TNF and its production by peripheral blood mononuclear cells (PBMNC); (b)serum levels of neopterin, a product that reflects endogenous IFN production; (c) resting and activated lymphocyte subpopulations; and (d)serum levels of soluble interleukin-2 receptor (IL-2R). Serum levels of IFN and TNF did not differ significantly in untreated and treated SAA patients and control individuals. Spontaneous and phytohemagglutinin-induced production of IFN and TNF by PBMNC, however, were highly increased in both untreated and treated SAA patients. Increased and decreased neopterin serum levels in untreated and treated SAA patients, respectively, suggest modulation of endogenous lymphokine release subsequent to immunosuppression. HLA-DR + antigen was mainly expressed by CD8 T cells. Circulating numbers of activated (CD4 and CDS)T cells and serum levels of IL-2R were not increased in both untreated and treated SAA patients. The proportion of HLA-DR + T cells in the PBMNC of untreated SAA patients correlated with the extent of lectin-induced IFN production. Although we were unable to confirm previous reports in SAA on (a)detectable IFN in blood and bone marrow serum, (b)improvement of stem cell growth upon neutralization of endogenous IFN, (c)absolutely increased numbers of circulating activated T cells, and (d)normalization of these abnormalities subsequent to successful immunosuppression, our data clearly support previous reports on abnormal lymphokine production in severe aplastic anemia. Our failure to relate this phenomenon to the severity of disease states, however, further raises doubts on the pathogenetic significance of lymphokine overproduction in SAA.

Levels of glycosylated hemoglobins (GHb) are significantly (p < 0.0005) lower in patients with hemolytic anemia (n= 20; mean = 3.9% ± 0.1 % SD GHb of total Hb) compared to patients with nonhemolytic anemia (n= 20; mean = 7.0% ± 0.7% GHb) and normal controls (n= 30; mean = 6.7% ± 0.7% GHb). A curvilinear correlation between GHb and red cell survival is demonstrable (n= 20; r2= 0.88; p< 0.001). Determination of GHb may be useful as a screening test for hemolytic anemia and for the evaluation of the degree of hemolysis, provided that diabetes mellitus can be excluded.

99mTc-DMPE was used for myocardial scintigraphy in ten patients with coronary artery disease. As in 201Tl studies regional activity of 99mTc-DMPE was reduced in infarcted myocardium. However, activity accumulation of 99mTc-DMPE in the heart was faint, while that in the liver was prominent. The activity ratio of heart to liver improved with time, whereas that of heart to lung decreased. The scintigraphic quality was considerably worse in 99mTc-DMPE studies than in those with 201Tl, due to high background activity. Also the visualization of the ribs and sternum interfered with the interpretation of the scintigrams. From these results it appears that 201Tl remains still the agent of choice for myocardial perfusion scintigraphy.