Serum albumin (SA) accumulation by bronchogenic tumours: a tracer technique may help with patient selection for SA-delivered chemotherapy

Systemic toxicity and inadequate tumour uptake of chemotherapeutic agents limit effective therapy of disseminated malignant disease. We seek to use macromolecules for improved delivery of therapeutic agents to tumours, and hope to use radiotracer procedures to identify those malignancies able to accumulate the transport molecule. A literature search identified in vitro and animal experimental data which indicated that serum albumin is taken up in malignancies. Selected cytostatic drugs can be bound to albumin, which suggests the suitability of the molecule as a potential transport vehicle. We therefore evaluated indium-111 labelled human serum albumin (HSA) to determine the frequency of its accumulation in bronchogenic tumours. Single-photon emission tomographic (SPET) images were obtained in 23 patients 48 h after intravenous injection of 1.5 mCi¹¹¹In diethylenetriamine penta-acetic acid (DTPA)-HSA. SPET imaging with technetium-99m labelled erythrocytes was included in the protocol to assess the influence which vascularity has on the HSA-based images. All patients went on to surgery. We documented the histological diagnosis, T-stage and differentiation grade. The scintigraphic examination demonstrated HSA uptake in three squamous cell carcinomas and four adenocarcinomas. Of these, six malignancies accumulating HSA had 2.2–5.4 times the tracer concentrations observed in comparable background regions. Small cell carcinoma failed to accumulate the labelled HSA during the 2-day scintigraphic evaluation. The HSA images did not appear to represent tumour vascularity. T-stage and differentiation grade failed to predict which tumours would demonstrate HSA uptake. Initial results suggest that HSA merits evaluation as a potential transport molecule for inmour-directed therapeutic agents, since approximately 35% of the examined malignancies showed HSA uptake. At the same time the relatively infrequent tumour HSA incorporation may mandate using scintigraphy and labelled HSA for selecting those individuals who may profit from HSA-delivered drug therapy. The described selection and therapy approach was tried in two patients who had an¹¹¹In-DTPA-HSA tumour to background ratio of 1.45:1 and 5.3:1 respectively. Both received experimental chemotherapy with methotrexate (MTX)-HSA.     

Rhenium-186 hydroxyethylidenediphosphonate (186Re HEDP) for the treatment of hemophilic arthropathy: first results

OBJECTIVES: The aim of this study was to evaluate the efficacy of a systemic application of rhenium-186 hydroxyethylidenediphosphonate (Re HEDP) for pain treatment in patients with hemophilic arthropathies. METHODS: Twelve patients with hemophilic arthropathy with at least 3 involved joints with persistent pain were included in this prospective study. A single dose of 15 mCi (555 MBq) Re HEDP was administered intravenously. Before and 12 weeks after treatment, pain assessment was performed using the visual analog scale (VAS). The pain status assessment included the general status, pain of all joints affected, and pain of the 3 mostly involved joints. Furthermore, quality of life was assessed. RESULTS: With regard to the 3 most involved joints, an improvement of the pain symptoms in 25 of 36 (69.4%) joints was observed. With regard to all involved joints a median of 3 joints per patient improved after Re HEDP therapy. General pain status after treatment was 2.0 VAS points lower as compared with pretreatment. The total number of involved joints remained unchanged in 7 patients, increased in 1 patient, and decreased in the remaining 4 patients. CONCLUSIONS: The results of this study show an improvement of the pain symptoms of the involved joints 12 weeks after therapy with Re HEDP in patients with hemophilic arthropathy. The only moderate success regarding a reduction of the total number of involved joints is by the fact that despite this improvement most affected joints remained still painful on a lower level after the therapy or due to newly affected joints not painful before initiation of the radionuclide therapy.     

Heart-rate recommendations: transfer between running and cycling exercise?

With the expanding use of portable heart rate (HR) monitors in endurance sports, HR is increasingly used as a marker for exercise intensity. Hereby, HR at the so-called individual anaerobic threshold (IAT) is one possible reference point. However, once determined, it is often attempted to apply HR recommendations from one type of ergometry to different kinds of exercises. We examined whether HR at IAT and at 4 mmol x l -1 blood lactate is predictable from cycling to running and vice versa. Data of 371 subjects (304 male, 67 female) were analyzed. All subjects underwent an incremental test on a treadmill (TR, starting speed 6 or 8 km x h -1, increments 2 km x h -1 every 3 min) and on a bicycle ergometer (BE, start at 50 Watt, increments 25 or 50 Watt every 3 min). IAT was determined at a net increase of lactate concentration of 1 - 5 mmol x l -1 above lactate concentration at lactate threshold for running (as in: Med Sci Sports Exerc 1998, 30 (10); 1552 - 1557) and 1.0 mmol x l -1 for cycling. A maximum time span of three weeks was allowed between the tests. We found that heart rate at IAT or at 4 mmol x l -1 blood lactate did not correlate between cycling and running. A sports specific test seems to be a prerequisite for reliable heart rate recommendations.     

Form, size and function of the sports heart--differentiation from pathological findings

Dependent on the nature, intensity and scope of muscular exercise, regular athletic training can result in changes in the size and form of the heart, which can be recorded by radiologic and echocardiographic techniques. Brief anaerobic exercise and purely static forms of training (sprint, strength sports) do not produce substantial increases in the size of the heart, but a rotund heart shape with rounding of the cardiac tip and in some cases a discrete increase in the wall thickness of the ventricular myocardium is frequently observed. Dependent on the scope of the training and the intensity, aerobic, endurance-oriented training (endurance sports) can induce considerable enlargement of all cardiac chambers with a change in the cardiac configuration, which is most nearly comparable to combination mitral vitium. Comparison of physiological hypertrophy of the athletic heart with pathological forms of cardiac hypertrophy (such as cardiomyopathies) is in many cases not unequivocally possible with plain X-ray films, but it is usually successful with echocardiographic examination methods.     

Kr-81m for determination of right ventricular ejection fraction (RVEF)

A 10–12 mCi ⁸¹Rb^81mKr generator was connected to a specially designed short-period infusion set, to produce an equilibrium activity distribution in the right heart. This procedure was tested in 25 individuals to calculate the right ventricular ejection fraction (RVEF). On average 30 heart cycles were analyzed per study. No background activity from the left heart was visualized because of the radionuclide exhalation. The background from the lungs could be neglected, which is partially due to the ultrashort half-life of the nuclide (t _1/2=13s). Thus, an easy automatic procedure can be applied to delineate the ventricle and to calculate the RVEF. The data showed excellent reproducibility, when investigations were repeated. The method would benefit from use of higher activity generators.     

Ventilatory, lactate-derived and catecholamine thresholds during incremental treadmill running: relationship and reproducibility

Anaerobic threshold as a basic criterion of training recommendation can be estimated by various parameters. The purpose of this study was to investigate the relationship and the reproducibility of ventilatory, lactate-derived and catecholamine thresholds of an incremental treadmill exercise. Therefore, 11 male subjects underwent two incremental treadmill tests within 7 days. The lactate threshold (LT) was determined at the lowest value of the lactate-equivalent (ratio lactate/performance). The individual anaerobic threshold (IAT) was calculated at LT+1.5 mmol/L lactate. The ventilatory thresholds, using mass-spectrometry, were defined by the V-slope method (AT) and at the deflection point of end-tidal CO2 (ET-CO2) concentration (RCP). The thresholds of epinephrine (TE) and norepinephrine (TNE) were calculated in the manner of LT. The running velocities were highly reproducible at LT (test-retest correlation coefficient r=0.90), IAT (r=0.97), AT (r=0.88) and RCP (r=0.95). By contrast TE (r=0.49) and TNE (r=0.46) showed a poor reproducibility. TE and TNE occurred 5-11% below LT and AT with a low correlation to LT and AT. LT was found 4% below AT, both were correlated with r=0.70 (p<0.01, test 1) and r=0.95 (p<0.01, test 2). IAT occurred 7-8% above RCP, in both tests a close correlation was found between IAT and RCP of r=0.97 (p<0.01). In summary, the ventilatory and lactate-derived thresholds show a high and similar reproducibility, but the catecholamine threshold does not. In the present exercise protocol, there are systematic differences between the lactate-derived and ventilatory thresholds, in spite of a close relationship, and these must be taken into account in recommendations derived for training.