131I-metaiodobenzylguanidine and 125I-iodoamphetamine

Radioiodinated metaiodobenzylguanidine (MIBG) has been shown to be extracted in the lung by an active, sodium-dependent, saturable transport system similar to that which extracts norepinephrine. Accordingly, first transit uptake of MIBG has been investigated as a method for in vivo evaluation of pulmonary biogenic amine metabolism. Issues that still must be resolved include the degree to which MIBG extraction is affected by simple loss of available vascular surface (in distinction to changes in amine metabolism). If MIBG lung extraction is altered by loss of pulmonary vascular surface alone, then a tracer must be found that can serve as a simultaneous monitor of vascular surface loss in order to allow normalization of the MIBG data. One tracer with such potential is radioiodinated iodoamphetamine (IMP). Accordingly, an experimental model of pulmonary vascular surface loss (lobar ligatures) was applied in an isolated-perfused lung model with simultaneous administration of MIBG and IMP. A linear relationship was found between MIBG extraction and percent lung surface loss by weight (n=21, r=0.75, P0.05). Addition of IMP (1 or 10 M) to media containing MIBG (1 M) (n=28) inhibited overall MIBG extraction, but decreases in MIBG uptake with vascular surface loss were otherwise parallel to those in experiments without IMP. IMP, however, did not adequately reflect vascular surface loss at the concentrations used in this study (extraction of IMP 1 M=31.2±12.9% in control vs 32.7%±7.7% with greater than 50% lung surface loss, n=18, P=NS). The results indicate that a correction for vascular surface loss is needed to interpret MIBG results in vivo, but suggest that IMP is not able to serve this purpose.Supported in part by the Swiss National Foundation for Scientific Research under cotract no 3.985-0.86     

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

Purpose Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means.Methods One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF 40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with ¹⁵O-labelled water (H₂¹⁵O) and ¹⁸F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (0.6 ml min^–1 g^–1) were classified as stunned, and segments with reduced MBF (<0.6 ml min^–1 g^–1) as hibernating if MRG was 0.25 mol min^–1 g^–1. Segments with reduced MBF and MRG <0.20 mol min^–1 g^–1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 mol min^–1 g^–1 as non-transmural scars.Results Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 mol min^–1 g^–1) and 233 (39%) reduced MRG (0.16±0.05 mol min^–1 g^–1). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 mol min^–1 g^–1) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min^–1 g^–1), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min^–1 g^–1 and 0.48±0.08 ml min^–1 g^–1, respectively), and lowest in transmural scars (0.40±0.14 ml min^–1 g^–1, P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40±0.19 mol min^–1 g^–1 vs 0.46±0.20 mol min^–1 g^–1, NS), and lowest in stunned myocardium with reduced MRG and transmural scars.Conclusion Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.     

Evaluation of 111In labelled white blood cells by in vitro functional tests and electron microscopy

We have studied the influence of granulocyte labelling with commercially available ¹¹¹In-oxine, tropolone (trop) or home made ¹¹¹In-Mercapto pyridine (Merc) prepared by the method of Thakur (1985) on the cell structure by electron microscopy and on the cell function by enzymatic tests, random migration, chemotaxis, phagocytosis and bactericidal activity. The granulocytes were labelled with 400 Ci ¹¹¹In-oxine in saline or ¹¹¹In-trop or Merc in plasma. The effect of the chelating agents with and without addition of the tracer was studied (n=4) with varying concentrations: 5–10 g/ml oxine, 10–160 g/ml trop and 1–4 g/ml Merc. Chemotaxis and random migration were not affected by ¹¹¹In-trop and clearly supressed by ¹¹¹In-oxine and Merc; the other tests were normal. The cell structure was disturbed by Merc. The labelling efficiency was excellent with oxine (90%), acceptable with trop (30%–80%) and poor with Merc (10%–25%). Without ¹¹¹In, chemotaxis and random migration were normal up to a concentration of 80 g/ml trop, 8.5 g/ml oxine and 1 g/ml Merc. With addition of ¹¹¹In, chemotaxis and random migration were unaffected up to 80 gmg/ml by trop and markedly supressed by Merc and oxine. It is concluded that labelling with ¹¹¹In-trop assures intact cells.     

Effect of adrenergic receptor ligands on metaiodobenzylguanidine uptake and storage in neuroblastoma cells

The effects of adrenergic receptor ligands on uptake and storage of the radiopharmaceutical [¹²⁵I]metaiodobenzylguanidine (MIBG) were studied in the human neuroblastoma cell line SK-N-SH. For uptake studies, cells were incubated for 15 min with varying concentrations of -agonist (clonidine, methoxamine, and xylazine), -antagonist (phentolamine, tolazoline, phenoxybenzamine, yohimbine, and prazosin), -antagonist (proranolol, atenolol), -agonist (isoprenaline and salbutamol), mixed / antagonist (labetalol), or the neuronal blocking agent guanethidine, prior to the addition of [¹²⁵I]MIBG (0.1 M). The incubation was continued for 2 h and specific cell-associated radioactivity was measured. For the storage studies, cells were incubated with [¹²⁵I]MIBG for 2 h, followed by replacement with fresh medium with or without drug (MIBG, clonidine, or yohimbine). Cell-associated radioactivity was measured at various times over the next 20 h. Propanolol reduced [¹²⁵I]MIBG uptake by approximately 30% (P<0.01) at all concentrations tested, most likely due to nonspecific membrane changes. However, incubation with the other -agonists or antagonists failed to elicit significant reductions in uptake. In contrast, all of the -agonists significantly inhibited uptake (P<0.05); guanethidine >xylazine >clonidine=methoxamine. The -antagonists demonstrated a broad range of inhibition (phenoxybenzamine phentolamine prazosin yohimbine=tolazoline)(P<0.05). The mixed ligand, labetalol, inhibited MIBG uptake in a dose-dependent manner with an apparent IC₅₀ of 0.65 M. The retention studies demonstrated that unlabeled MIBG caused profound self-inhibition (P<0.01). Clonidine produced a modest inhibition of retention and yohimbine had no effect. Labetalol, phenoxybenzamine, guanethidine, and propranolol reduced uptake of [¹²⁵I]MIBG by neuroblastoma cells in culture. Although only labetalol has been reported to cause false-negative MIBG scans, our results suggest that these other drugs have the potential to interfere with MIBG imaging and therapy, particularly at high doses. Adrenergic drugs did not alter cytoplasmic retention of [¹²⁵I]MIBG in neuroblastoma cells but may have potential in tumors such as phenochromocytoma, where granular storage of MIBG has been observed. Inhibition of [¹²⁵I]MIBG retention by unlabeled MIBG supports the use of high specific activity radioiodinated MIBG for both diagnosis and therapy.     

Metabolism of ingested 14C-triolein

To estimate the radiation dose of ingested ¹⁴C- (and ³H-) labelled fatty acids, we measured ¹⁴CO₂ in samples of expired air in five subjects, and serum ¹⁴C activity in four subjects, over 4 weeks. These investigations showed that 25%–40% of ingested ¹⁴C-fatty acids were metabolized and expired as ¹⁴CO₂ within 10 days after ingestion. The residue was expired with a calculated half-life of 493 days. Six days after ingestion of the radiolipids, radioactivity in serum was barely detectable. From these data of ¹⁴C-fatty acid metabolism, a total whole-body radiation of 20 mrem/Ci ¹⁴C, 8 mrem/Ci¹⁴C the first years, was calculated. The corresponding radiation dose for ³H-fatty acid was 2 mrem/Ci ³H and 1 mrem/Ci ³H respectively. Maximal organ-specific radiation (gonads and lungs) from the blood-borne radioactivity was 1 mrem/Ci of ¹⁴C-fatty acid.     

Lung uptake of 131I-metaiodobenzylguanidine in sheep

Circulating biogenic amines are known to be cleared by the mammalian lung. Their lung uptake is considered as an indicator of pulmonary endothelial integrity. Unfortunately, their use as markers of pulmonary metabolic function in human pathology is precluded by their biological effects and by the type of radiolabeling (³H and ¹⁴C), making them harmful for repeat injections and unfit for scintigraphy. Metaiodobenzylguanidine (MIBG) is structurally related to the neuron blocking agent guanethidine, devoid of significant biological effects, and has been shown to be extracted by the same active sodium dependent, saturable transport as norepinephrine in perfused rat lungs in vitro. We studied the single pass lung extraction of ¹³¹I-MIBG in five awake and five anaesthetised sheep using the standard double indicator dilution technique with ^99mTc-human serum albumin (HSA) as an intravascular reference tracer. Intravenous bolus injection of increasing doses of MIBG up to 400 nmol resulted in a significant (F ratio=7.778, P<0.0001) dose dependent decrease of MIBG extraction in both awake and anaesthetised sheep, without significant differences of extraction values between the two groups. For the 10 sheep, the averaged percentage single pass pulmonary uptake of MIBG at the peak of the dilution curve decreased from 32%±3% (mean±SE, n=27 measurements) with 20 nmol to 18%±2% (n=32) with 400 nmol. Estimates of the apparent Michaelis-Menten constant (K _m) averaged 2±1.2 M (n=7), whereas estimates of the apparent maximum velocity of removal (V _max) was 1.1±0.5 mol/min (n=7). In contrast to some intersubject variability, the pharmacokinetic parameters showed little intra subject variation. No correlation was found between MIBG extraction, K _m or V _max values and haemodynamic or gas exchange parameters. These data indicate that using a standard double dilution technique, lung extraction of MIBG may be determined in vivo. Its lung removal is dose limited and may be characterised by the Michaelis-Menten kinetic constants suggesting a saturable process. In contrast to norepinephrine, the gamma emitter labeled MIBG could therefore be a suitable compound to monitor pulmonary endothelial cell function in vivo using a non invasive scintigraphic method.Supported by the Swiss National Fundation for Scientific Research under contract No 3.985-0.86     

125I-β-iodo-D-alanine-synthesis,biodistribution and antimicrobial activity

Methyl N-carbobenzoxy--iodo-D-alaninate (1) served as an intermediate to synthesize methyl -iodo-D-alaninate (2) and -iodo-D-alanine (3). The ¹²⁵I-labeled compound 1 was synthesized by the melt method and used to synthesize ¹²⁵I-labeled compounds 2 and 3. Compound 3 was shown to be substrate for D-amino acid oxidase. It was also shown that compounds 2 and 3 were rapidly eliminated from normal mammalian tissues and that compound 3 inhibited the Escherichia coli growth in a dose-dependent manner at 100–500 g/ml while compound 2 showed no effect at 500 g/ml level. Therefore, it was suggested that compound 3 may serve as an abscess localizing agent.Research carried out at Brookhaven National Laboratory under contract with the U.S. Department of Energy (No. DE-AC-02-76CH00016) and supported by its Office of Health and Environmental Research     

Further investigations of morpholino pretargeting in mice—establishing quantitative relations in tumor

Purpose This laboratory has previously published on phosphorodiamidate morpholino (MORF) pretargeting of tumor in which an anti-tumor antibody conjugated with MORF (a DNA analogue) is first administered, followed at a later time by the radiolabeled complementary MORF (cMORF) as the effector. In the present study, the pharmacokinetics of the antibody and effector were measured under different conditions in mice to establish their quantitative relationships with tumor accumulations by pretargeting.Methods A cytosine-free 18 mer cMORF was conjugated with MAG₃ for ^99mTc labeling while the anti-CEA antibody MN14 was conjugated with DTPA for ¹¹¹In labeling and with MORF to impart binding affinity for radiolabeled cMORF. Mice bearing LS174T thigh tumors were used to study: (1) the pharmacokinetics of MN14-MORF by administering ¹¹¹In-MN14 at doses between 10 and 100 g with sacrifice at 2 days and at 30 g with sacrifice between 1 and 3 days; (2) the biodistribution of ^99mTc-cMORF following one to four injections (containing 0.15 g each and separated by 1 h) to animals having received 30 g of antibody–MORF 2 days earlier and with sacrifice at 3 h after the final injection; and (3) the influence on the biodistribution of ^99mTc-cMORF of a 2 to 4 day interval between the administration of 30 g of antibody–MORF and 0.30 g of ^99mTc-cMORF.Results (1) The biodistribution of antibody in percent accumulation (%ID or %ID/g) was largely independent of antibody dose but the absolute accumulation of antibody in tumor increased linearly with dose, showing no evidence of tumor saturation of CEA sites by MN14. Over 1–3 days post antibody administration, blood levels of radiolabeled antibody decreased as expected; however, tumor levels remained constant, thus showing an absence of antibody clearance in tumor over this period. (2) With fixed antibody–MORF dose and increasing number of injections of ^99mTc-cMORF, cumulative percent blood levels steadily decreased in agreement with the values calculated based on the antibody–MORF in blood. In contrast, cumulative percent tumor levels stayed fairly constant over the first two injections. Thus the antibody–MORF in tumor became saturated with cMORF more slowly than that in blood owing to delivery differences. (3) As expected, percent blood levels decreased with increasing interval between injections of antibody–MORF and ^99mTc-cMORF. The percent tumor accumulation, however, remained constant over the 3 day interval, thus demonstrating only slow loss of MORF expression in situ. The ^99mTc-cMORF accumulation in tumor after saturation was mathematically determined based on the antibody–MORF concentration in tumor while the blood levels of ^99mTc-cMORF were determined based on the concentration of antibody-MORF in blood.Conclusion Contrary to conclusions arrived at in our earlier study, the results of this study show that tumor CEA sites were not saturated even at the highest antibody dose investigated, that accessibility of MORF sites in tumor by ^99mTc-cMORF was unhindered and that the maximum percent tumor accumulation of ^99mTc-cMORF depended only on the tumor delivery efficiency of ^99mTc-cMORF.     

Improvement of brain single photon emission tomography (SPET) using transmission data acquisition in a four-head SPET scanner

Attenuation coefficient maps (-maps) are a useful way to compensate for non-uniform attenuation when performing single photon emission tomography (SPET). A new method was developed to record single photon transmission data and a-map for the brain was produced using a four-head SPET scanner. Transmission data were acquired by a gamma camera opposite to a flood radioactive source attached to one of four gamma cameras in the four-head SPET scanner. Attenuation correction was performed using the iterative expectation maximization algorithm and the-map. Phantom studies demonstrated that this method could reconstruct the distribution of radioactivity more accurately than conventional methods, even for a severely non-uniform-map, and could improve the quality of SPET images. Clinical application to technetium-99m hexamethylpropylene amine oxime (HMPAO) brain SPET also demonstrated the usefulness of this method. Thus, this method appears to be promising for improvement in the image quality and quantitative accuracy of brain SPET.This work was presented in part at the World Congress on Medical Physics and Biomedical Engineering, 7–12 July 1991, Kyoto, Japan     

Radiation doses to those accompanying nuclear medicine department patients: a waiting room survey

In a multi-centre European trial we have assessed the radiation dose to those accompanying patients undergoing nuclear medicine investigations. Dosemeters were first calibrated against each other and then used to measure the radiation dose to the nurse or relative while they were in the waiting room. In departments where there was one waiting room the median radiation dose was 13 LSv, and the corresponding figures for where there were two waiting rooms and where the patients were allowed to leave the department with their nurse or relative were 12 and 11 Sv, respectively. These figures are not significantly different. However, we found that the median radiation dose to relatives was 13 Sv while that to nurses was 3 Sv (P<0.01), although the waiting times were not significantly different. The reasons for these differences are discussed. Our data do not support the need for a second waiting room for injected patients in a nuclear medicine department. Correspondence to: L.K. Harding     

Local Administration of NF-κ B Decoy Oligonucleotides to Prevent Restenosis after Balloon Angioplasty: An Experimental Study in New Zealand White Rabbits

Purpose To evaluate the efficacy of NF- B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits.Materials and Methods In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF- B in two different concentrations (1 g: n=14; 10 g: n=8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed.Results NF- B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF- B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm² using 1 g NF- B ODN compared to 0.98 mm² in the control group. The higher dose resulted in a neointimal area of 0.97 mm² compared to 1.07mm² at the control side.Conclusions Local drug delivery of NF- B ODN using the channeled balloon catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.     

Interaction of metaiodobenzylguanidine with cardioactive drugs: an in vitro study

Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [¹²³I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [¹²⁵I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [¹²⁵I]MIBG uptake, whereas all other drugs tested (other -blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 M. The labetalol dose inhibiting 50% of [¹²⁵I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [¹²³I]MIBG in treated patients, provided that plasma concentration is taken into account.     

Bromine-82 contamination in fission product 99mTc-generator eluate

Following receipt of fission product ^99mTc-generators, results of radionuclide purity analysis, performed within 30 min after the first elution, demonstrated detectable levels of a contaminate radionuclide not previously reported. Gamma spectroscopy and half-life determinations confirmed the presence of ⁸²Br. Bromine-82 activity, in eluates from the first elution of 30 generators, received weekly during a 7-month period, ranged from 0.22 Ci (8.235 kBq) to 0.67 Ci (24.68 kBq) per eluate. The ratio of ⁹⁹Mo to ^99mTc ranged from 0.13 nCi to 0.39 nCi per mCi ^99mTc. The presence of ⁸²Br in ^99mTc-generator eluate resulted in falsely elevated ⁹⁹Mo assay determinations using whole vial ⁹⁹Mo assay procedures. For every 0.1 Ci ⁸²Br present in ^99mTc eluate the ⁹⁹Mo assay results were elevated by 1 Ci. Gamma spectroscopy of eluates from additional elutions of these generators failed to detect the presence of ⁸²Br demonstrating the displacement of monovalent bromine anions from the alumina column during the first elution.     

Fluorodeoxyglucose cell incorporation as an index of cell proliferation: evaluation of accuracy in cell culture

The use of fluorodeoxyglucose (FDG) and positron emission tomography (PET) is recognized as an accurate tool for the specific diagnosis and staging of cancer. It has also been proposed for the monitoring of anticancer therapy. FDG cell incorporation reflects glycolytic activity whereas inhibition of cell proliferation corresponds to an efficient cancer treatment. The relationship between FDG incorporation and cell proliferation has yet to be demonstrated. Therefore, we aimed to correlate the effects of the toxic agents bleomycin and unlabelled meta-iodobenzylguanidine (mIBG) on cellular metabolism and proliferation. We determined the in vitro metabolic and cytotoxic effects of bleomycin and mIBG by measuring the incorporation of fluorine-18 FDG (%U_FDG) and hydrogen-3 thymidine (%U_THY) in cells of the human premonocytic line U937 in the presence of increasing concentrations of these agents. Proliferation rate of these cells was studied by means of limiting dilution analysis. %U_THY appeared more sensitive to bleomycin or mIBG-mediated cell injury than %U_FDG. After 1 h of exposure to 0.5 M bleomycin, %U_THY was significantly reduced to 62.0% ± 10.4% of control value whereas %U_FDG remained unchanged (91.6% ± 5.3%). Similar results were obtained after 1 h of exposure to increasing concentrations of mIBG (1 M to 1 mM). After 20 h of exposure to bleomycin, %U_THY and %U_FDG were significantly reduced as a function of concentration. After 20 h of exposure to mIBG, a transient increase in %U_FDG up to 149.3% ± 11.2% with 50 M mIBG was further followed by a reduction to 20.1% ± 6.7% with 0.5 mM (P < 0.001). The clonogenic efficiency was reduced as a function of bleomycin (ANOVA, n=255, P) or mIBG concentration (n=80, P) and nearly abolished with 0.1 M bleomycin or 0.1 mM mIBG. In conclusion, %U_THY appears to be a more sensitive index of cytotoxicity in vitro and more accurately relates to cell proliferation than %U_FDG. Correspondence to: D.O. Slosman, Nuclear Medicine Division, Geneva University Hospital, CH-1211 Geneva 14, Switzerland     

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis

The level of the aminoterminal propeptide Col 1–3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6±1.1 g/l; N: 8.6±1.8 g/l), while significantly increased levels were found in PMF (24.8±2.2 g/l).During a follow-up of 1 year, a slight increase of 2 g/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 g/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as -thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide.These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.     

Genetic polymorphism of desialyzed alpha2 HS-glycoprotein by ultrathin isoelectric focusing

Summary The genetically determined polymorphism of ₂ HS-glycoprotein was analyzed by immunoblotting ultrathin-layer polyacrylamide gel isoelectric focusing in the pH range 4–6.5 and neuraminidase pretreated sera. In a Libyan population sample from Tripoli (n=110) three common phenotypes, ₂ HSG 1–1, 2–1, and 2–2, were observed. The allele frequencies were ₂ HSG¹=0.8364 and ₂ HSG²=0.1636. The theoretical exclusion rate in cases of disputed paternity is 11.8%.     

A comparison of dobutamine and maximal exercise as stress for thallium scintigraphy

In the assessment and evaluation of patients with suspected coronary artery disease there is a need for pharmacological stress combined with thallium scintigraphy. Thallium images were obtained following stress both with dobutamine infusion (5–20 g kg^–1 min^–1) and with symptom-limited bicycle ergometry in 20 patients (age 39–70 years) with chest pain who had been admitted for coronary angiography. Percentage thallium uptake was calculated using a region of interest technique. Detailed comparison was performed of the presence, size and distribution of left ventricular thallium perfusion defects; the percentage thallium uptake in ventricles, lung and liver; and the haemodynamic response to stress. Each stress produced a similar number of abnormal segments in each of three views (total EX 166/300; DOB 167/295), but exercise produced larger defects in the anterior view (P<0.025). Thallium uptake in left and right ventricles and relative uptake to lungs were similar, but dobutamine produced higher relative liver uptake [EX 1.55 (0.67); DOB 2.97 (1.23) P<0.0001]. Fourteen patients were able to tolerate dobutamine 20 g kg^–1 min^–1. The ratio of peak stress to rest double product was smaller with dobutamine in both patients with (DOB 1.3; EX 2.0; P<0.0047) and patients without -blockade (DOB 1.5; EX 2.4; P<0.008). Dobutamine produced fewer conventional stress endpoints of chest pain and ST depression. In conclusion, dobutamine produces a well-tolerated incremental pharmacological stress with thallium images similar to maximal exercise, and provides a useful alternative stress in patients unable to perform adequate dynamic exercise.Correspondence to: D.R. Wallbridge     

A simple radioaerosol generator and delivery system for pulmonary ventilation studies

Details of a simple radioaerosol generator and delivery system are presented. Aerosol streams of ^99mTc-DTPA solution of different distributions were produced. The most useful distribution had an activity median aerodynamic diameter (AMAD) of 0.9 m with a geometric standard deviation of 1.5. This distribution also had more than 96% of aerosol particles with aerodynamic diameter <2 m. The system has been used for patient lung ventilation studies. The aerosol breathing-in period to achieve a satisfactory count rate was 1.8±0.38 min. The radioaerosol images were excellent and comparable to those obtained with ^81mKr gas.     

Todeszeitbestimmung auf der Basis simultaner Messung von Hirn- und Rektaltemperatur

Zusammenfassung Die Analyse der Daten an 21 Leichen simultan registrierter Hirn- und Rektaltemperaturkurven ergab hinsichtlich separater oder kombinierter Todeszeitberechnungen folgende Ergebnisse und Schlußfolgerungen:Im Bereich einer normierten Hirntemperatur (Q _H) 0,5Q _H<1,0 (etwa bis 6,5 hpm) führt die alleinige Verwendung der Hirntemperatur zu den präzisesten Todeszeitrückrechnungen (Standardabweichung um dt=0 s ₀=±0,75; Variationsbreite 3,3 h). Im Bereich 0,3Q _H<0,5 (etwa 6,5–10,5 hpm) ist die kombinierte Todeszeitrückrechnung mit Wichtung im Verhältnis 6 (Hirn):4 (Rektum) vergleichsweise am präzisesten (s ₀=±1,18; Variationsbreite 5 h). Im Bereich 0,07Q _H<0,3 (jenseits 10,5 hpm) ergibt die alleinige Verwendung der Rektaltemperatur die präzisesten Todeszeitberechnungen (s ₀=±1,62; Variationsbreite 6,6 h).Ein integrierter Rechenansatz aus beiden Rückrechnungsformeln mit dadurch möglicher Elimination der Temperatur bei Todeseintritt scheint im Bereich um 0,7Q _H<1,0 geeignet zu sein, größere Fehler berechneter Todeszeiten in Fällen mit z.B Fieber bei Todeseintritt zu vermeiden (s ₀=±0,69; Variationsbreite 2,7 h).Herrn Prof. Dr. W. Janssen zum 60 Geburtstag gewidmet     

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of ¹³¹I (259–3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean±SD) were 3.19±0.93, 10.83±1.72 and 5.75±2.06, respectively, in the whole group, and these values differed significantly from each other (P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a damage ratio (DR) and a recovery ratio (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%±11.5% vs 67.6%±9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%±24.4% vs 36.8%±13.7%). The DR on the 3rd day was not related to the administered ¹³¹I dose in the whole group, but a negative correlation was found between the ¹³¹I dose and the RR at the 6th month (r=–0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x–28.4x²+38.1 (R²=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of ¹³¹I and DR and RR were obtained with a linear-quadratic model (Y=D+D²) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following ¹³¹I treatment. Further studies are therefore needed to clarify the effect of the negative value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of ¹³¹I treatment.