Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)ldt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [ · LV(0)], where is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while a is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min^–1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/1 [r = 0.82,n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

The kinetic basis of glomerular filtration rate measurement and new concepts of indexation to body size

As measurement of glomerular filtration rate (GFR) is now generally the responsibility of departments of nuclear medicine, it is important for nuclear medicine physicians and scientists to understand the pharmacokinetics of the indicators and radiotracers that are used, generally known as filtration markers. The single-injection, non-steady state technique is almost universally used, departments varying in how many blood samples are taken: rarely multisample clearance, which does not assume a single compartment of tracer distribution, commonly clearance based on a limited number of blood samples between 2 and 4 h after injection, which assumes a single compartment of distribution, and often a single sample at a defined time point. The volume of distribution, V _d , of a filtration marker is close to extracellular fluid volume (ECFV). GFR and ECFV are both overestimated by the assumption of a single compartment by amounts that are functions of the rate of plasma clearance, Z. Residence time, T, of tracer in its V _d is equal to V _d divided by Z. Z and T can both be measured from a multisample clearance curve, whereupon V _d is the product of Z and T. GFR is usually indexed to patient size by expressing it in relation to body surface area (BSA), which in turn is calculated from an equation based on the patients height and weight. An equation in common use was described by Haycock et al. and is BSA=0.024265×weight^0.5378×height^0.3964. An alternative indexation variable is ECFV. GFR per unit ECFV is close to the rate constant, ₃, of the terminal exponential of the plasma clearance curve. It is in fact slightly higher than this rate constant by an amount that is a function of the rate constant itself. The discrepancy between GFR/ECFV and ₃ arises from the development of a concentration gradient between interstitial fluid and plasma, which in turn produces an extrarenal veno-arterial gradient throughout the body. Indexing GFR to ECFV not only has physiological attractions (especially in children) but is technically simple because it requires measurement only of ₃ (slope-only technique). A disadvantage, however, is a lack of robustness in comparison with the conventional slope/intercept method, which measures tracer dilution as well as ₃. Nevertheless, the advantages of indexation to ECFV can still be exploited by changing the constants of an equation of the Haycock type so that the equation becomes a predictor of ECFV rather than BSA. A recently described equation is ECFV=0.02154×weight^0.6469×height^0.7236. Indexation to ECFV abolishes differences that arise between children and adults when GFR is indexed to BSA.     

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%.     

Determination of glomerular filtration rate (GFR) by analysis of capillary blood after single shot injection of 99mTc-DTPA

^99mTc-DTPA was prepared from a kit produced by the Institute of Atomic Energy, Oslo, Norway. Radiochemical purity as determined with gel chromatography ranged from 98.5–99.7% (n=7). The radiopharmaceutical showed no red cell uptake and not more than 0.2% protein binding in in vitro biokinetic studies.The clearance of ^99mTc-DTPA was compared to the clearance of ¹²⁵I-Iothalamate simultaneously using single shot intravenous injection and biexponential analysis of plasma activity disappearance rate according to Sapirstein et al. (1955). ¹²⁵I-Iothalamate was found to have a higher second volume of distribution than ^99mTc-DTPA, but there was no statistically significant difference in clearance.GFR calculated from capillary serum ^99mTc-DTPA count rates was in all subjects investigated virtually identical with GFR calculated from simultaneously collected venous plasma samples.Estimation of GFR on the basis of plasma activity curves obtained from sampling in two hours gave higher values than estimation from four hours sampling irrespective of kidney function and whether ^99mTc-DTPA or ¹²⁵I-Iothalamate was used.It is concluded that ^99mTc is almost entirely bound to DTPA after intravenous injection of the ^99mTc-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate, using both venous and capillary blood sampling.     

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of^99mTc-ECD. Hemispherical brain perfusion indices (BPI) for^99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for^99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between^99mTc-ECD BPI and^99mTc-HMPAO BPI and between^99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,^99mTc-ECD BPI was converted to¹³³Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of^99mTc-ECD were converted to rCBF maps using Lassen's correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for^99mTc-ECD SPET with those for^99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor of 2.6 gave nearly the same rCBF values for^99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for^99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in^99mTc-HMPAO studies is applicable to a^99mTc-ECD study for the measurement of rCBF without any blood sampling.     

The APE nebuliser — a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid

We report the validation of a new delivery system — aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 m and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV₁ 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of^99mTc DTPA, which was collected in a 351 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of^99mTc-DTPA. In view of the excellent intrapulmonary deposition of^99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.     

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. IV. Interaction of 99mTc-DMS and 99Tc-DMS complexes with blood serum proteins

As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals ^99mTc-DMS and ⁹⁹Tc-DMS with blood serum proteins was studied. The interaction of ^99mTc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins.After in vitro labelling of human sera with ^99mTc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65%±3.2% by gel-filtration chromatography; 72%±4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7%±6.8% and 71%±2.3%, respectively. Distribution of ^99mTc-DMS or ⁹⁹Tc-DMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with ^99m-Tc-DMS, while the same analysis was performed with ⁹⁹Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats.The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of ₂-, ₁- and ₁-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes.     

Using <Superscript>99m</Superscript>Tc-DTPA radioaerosol inhalation lung scan as compared with computed tomography to detect lung injury in blunt chest trauma

Background

Detection of pulmonary contusion in patients with blunt chest trauma is very important so as to commence therapy immediately to avoid irreversible damage. The purpose of our study was to evaluate the efficacy of technetium-99m diethylene triamine pentaacetic acid (^99mTc-DTPA) aerosol inhalation lung scintigraphy in comparison with chest computed tomography (CT) in the diagnosis of pulmonary contusion at acute blunt chest trauma.

Methods

Twenty-nine patients with isolated blunt chest trauma were referred to the emergency department of our hospital, and nine healthy people participated in this study. Sixteen patients who had pulmonary contusion on CT scans were referred to as group 1, and 13 patients who had normal CT scans as group 2. Nine healthy people comprised a control group. ^99mTc-DTPA aerosol inhalation lung scintigraphy was performed on the first day in all patients.

Results

The mean half time (T_½) and penetration index values of ^99mTc-DTPA clearance were significantly lower in groups 1 and 2 compared with the control group. Among the three groups, there were no significant differences in arterial blood gas analysis except for PO₂. The mean T_½ value of ^99mTc-DTPA clearance did correlate with PO₂ values but not with pH, PCO₂, or HCO₃ values.

Conclusions

^99mTc-DTPA radioaerosol inhalation lung imaging may serve as a useful adjunct and supportive method to chest CT scanning for detecting mild pulmonary contusion.

     

Estimation of glomerular filtration rate and technetium-99m diethylene triamine penta-acetic acid using chromium-51 ethylene diamine tetra-acetic acid

Simultaneous measurements of the clearance rate of chromium-51 ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) and technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) were performed in 54 patients with a range of function between 9 and 176 ml/min. Using multiple blood samples the two clearance values correlated well (r = 0.97, SEE 8.6 ml/min) and DTPA clearance was higher by 2.9%. For each radiopharmaceutical the plasma clearance rates obtained using multiple blood samples were compared with those obtained with simplified methods, i.e., the 60–180 min two-sample method of Russell and the mono-exponential method with the Brochner-Mortensen correction. For both radiopharmaceuticals the clearance values correlated well with the Russell method (r = 0.99, SEE = 4.1 ml/min for EDTA;r = 0.99, SEE 4.9 ml/min for DTPA) and the mono-exponential method (r = 0.99, SEE 3.6 ml/min for EDTA;r = 0.99, SEE 3.9 ml/min for DTPA). The mean plasma clearance obtained using multiple blood samples did not differ significantly from that obtained with the Russell method, either in patients with a glomerular filtration rate (GFR)<30 ml/min or in patients with GFR30 ml/min. The mean plasma clearance obtained using multiple blood samples differed significantly from that obtained with the mono-exponential method because of the great difference observed in patients with GFR30 ml/min. It is concluded that the Russell two-sample method after injection of^99mTc-DTPA is accurate enough for routine clinical use.     

A trial of semiquantitative analysis of whole body bone scintigraphy in renal osteodystrophy

Four color processed whole body bone scintigraphy with ^99mTc-methylene diphosphonate was performed in six patients on maintenance hemodialysis, and the results of semiquantitative colorimetric analysis were compared with those of a normal group. The difference between the two (control and patient group) was statistically significant (P<0.01). Furthermore, the effect of 1-hydroxyvitamin D₃ treatment on renal osteodystrophy was evaluated by this method. The results indicated that this method provides a useful method for assessing the response of renal osteodystrophy to treatment. Two representative cases of renal osteodystrophy are presented to illustrate the usefulness of this approach to semiquantitative whole body bone scanning.     

Pulmonary epithelial permeability in patients treated with bleomycin containing chemotherapy detected by technetium-99m diethylene triamine penta-acetic acid aerosol (99mTc-DTPA) scintigraphy

Purpose

To evaluate pulmonary epithelial permeability using^99mTc-DTPA scintigraphy in patients treated with bleomycin-containing regimens.

Material and Methods

Twelve nonsmoking chemotherapy-naive patients with no clinical or radiological evidence of pulmonary disease and treated with bleomycin-containing chemotherapy were tested with^99mTc-DTPA scintigraphy before the first cycle and every 3 weeks until the third month after the end of chemotherapy (total cumulative dose of bleomycin 347.9 mg).

Results

Pretreatment values (T1/2 74.93 minutes) of^99mTc-DTPA scintigraphy were significantly higher than those obtained after the total dose of bleomycin (T1/2 51.00 minutes) (p < 0.001). This difference was more important in the later evaluations especially, on the third week and third month measures after discontinuing treatment (p < 0.001). All the tests of Within-Subjects Effects were significant (p < 0.001). Comparing pretreatment and post-treatment scintigraphies the mean T1/2^99mTc-DTPA values decreased as the bleomycin dose increased.

Conclusion

We conclude that cumulative bleomycin doses are related to increased pulmonary epithelial permeability at a dose of 256.5 mg. However, whether this is related to clinical toxicity is uncertain and large, multi-center prospective studies are needed.     

Stability of α-[11C]methyl-l-tryptophan brain trapping in healthy male volunteers

Purpose The purpose of this study was to assess the reproducibility in healthy volunteers of -[¹¹C]methyl-l-tryptophan ([¹¹C]MT) brain trapping imaging with positron emission tomography (PET), using volumes of interest (VOIs) and voxel-based image analysis.Methods Six right-handed healthy male volunteers (34.3±10.9 years) with a negative family history for psychiatric disorders were scanned twice in the resting condition, 22±17 days apart. An unbiased semiautomatic segmentation of the brain was used to define VOIs. The trapping constant K* (ml g^–1 min^–1) for [¹¹C]MT was calculated for the whole brain and seven brain regions using the graphical method for irreversible tracers. In addition, parametric maps of K* were obtained from dynamic scans using the same method. Comparison of test and retest K* functional images was performed using SPM99. Students paired t statistic was applied for comparisons of [¹¹C]MT brain trapping in a priori selected VOIs.Results [¹¹C]MT brain trapping in VOIs showed a mean variability 2.6±1.8% (0.3–5%) for absolute and 1.5±2.1% (1.4–4.1%) for normalized K*. Intraclass correlations between test and retest conditions were 0.61±0.34 for absolute K* values and 0.73±0.20 for K* values normalized by global mean. SPM99 analysis using a height threshold of p=0.05 (two tailed) and an extent threshold of 100 voxels showed no significant differences between scans.Conclusion Rest measurements in healthy male volunteers of the trapping constant for [¹¹C]MT, using PET, appeared to be stable during an average interval of 3 weeks.     

White-matter disease in 18q deletion (18q−) syndrome: magnetic resonance spectroscopy indicates demyelination or increased myelin turnover rather than dysmyelination

Proton magnetic resonance spectroscopic data (¹H-MR spectroscopy) of patients with 18q deletion syndrome have not yet been reported. ¹H-MR spectroscopy, performed in an affected 2-year-old girl with markedly delayed neuromotor development and typical supratentorial white-matter disease (WMD), showed an increase of choline and -glutamate concentrations. Eight months later, simultaneously with clinical improvement, -glutamate had normalised whereas choline remained slightly increased. Active demyelination or increased myelin turnover might contribute to the hitherto unexplained WMD of this rare disorder.     

Assessment of alveolar epithelial permeability in Behçet’s disease with <Superscript>99m</Superscript>Tc-DTPA aerosol scintigraphy

Objective

Behçet’s disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1–10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible.

Methods

Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67 ± 8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87 ± 12.45 years) underwent ^99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of ^99mTc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 × 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of ^99mTc-DTPA clearance (T _1/2) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol.

Results

The clearance half time of ^99mTc-DTPA radioaerosols in the BD patients (24.81 ± 6.22 min) was faster than in the normal control group (46.53 ± 22.41 min) (P = 0.004). There was also a significant difference between PI of the patients with BD (0.15 ± 0.03) and that of the controls (0.21 ± 0.06) (P = 0.002). No correlation was found between the mean T _1/2 values of ^99mTc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PFT in the BD patients.

Conclusions

Lung epithelial permeability of the patients with BD was significantly higher than that of the normal subjects. The results of this study demonstrated that the assessment of lung epithelial permeability using ^99mTc-DTPA aerosol scintigraphy could predict the presence of lung involvement in the early stages of BD.

     

Application of the linear-quadratic model to myelotoxicity associated with radioimmunotherapy

The purposes of this study were: (1) to use the linear-quadratic model to determine time-dependent biologically effective doses (BEDS) that were delivered to the bone marrow by multiple infusions of radiolabeled antibodies, and (2) to determine whether granulocyte and platelet counts correlate better with BED than administered radioactivity, which does not take stem cell repopulation, i.e., time, into consideration. Twenty patients with B-cell malignancies that had progressed despite intensive chemotherapy and who had a significant number of malignant cells in their bone marrow were treated with multiple 0.7–3.7 GBq/m² (18–100 mCi/m²) intravenous infusions of Lym-1, a murine monoclonal antibody that binds to a tumour-associated antigen, labeled with iodine-131. Granulocyte and platelet counts were measured in order to assess bone marrow toxicity. BEDs were calculated according to the formula: BED=D(1+gD/(,/))–0.693(T _n–T _k/T _p, whereD represents the absorbed dose of radiation delivered to the red marrow by penetrating emissions of¹³¹I throughout the whole body and nonpenetrating emissions of¹³¹I in the blood and bone marrow,g is a factor that depends on the duration of irradiation relative to the repair half-life of human bone marrow, is the coefficient of nonrepairable damage per Gy, is the coefficient of repairable damage per Gy²,T _n is the time required to reach the granulocyte or platelet count nadir after an¹³¹I-Lym-1 infusion,T _k is the time at which bone marrow proliferation begins after the start of treatment andT _p is the doubling time of the bone marrow after the granulocyte or platelet count nadir has been reached. The cumulative¹³¹I-Lym-1 radioactivity administered to each patient was calculated. Biologically effective doses from multiple¹³¹I-Lym-1 infusions were summated in order to arrive at a total BED for each patient. There was a weak association between granulocyte and platelet counts and radioactivity (the correlation coefficients were –0.23 and –0.60, respectively). Likewise, there was a weak association between granulocyte and platelet counts and BED (the correlation coefficients were –0.27 and –0.40, respectively). The attempt to take bone marrow absorbed doses and overall treatment time into consideration with the linear-quadratic model did not produce a stronger association than was observed between peripheral blood counts and administered radioactivity. The association between granulocyte and platelet counts and BED may have been weakened by several factors, including variable bone marrow reserve at the start of¹³¹I-Lym-1 therapy and the delivery of heterogeneous absorbed doses of radiation to the bone marrow.     

Studies of 99mTc-acylplasmins as agents for thrombus detection

It has been proposed that acylation at the active site of plasmin is able to prevent its reaction with 2-antiplasmin without affecting the fibrin affinity of the enzyme. To investigate the possibility that ^99mTc-labelled acylplasmins are improved thrombus-detecting agents, six acylating agents were synthesised and their reaction with plasmin and the labelling of the products with ^99mTc studies. Uptake of ^99mTc-acylplasmins in an in vitro thrombus model was complicated by precipitation processes, which may in part account for the rapid blood clearance in rabbits and high liver uptake in mice injected with the compounds. Quantitative measurements using an in vivo rabbit thrombus model demonstrated that guanidinobenzoyl-plasmin exhibited nearly a threefold increase in thrombus uptake compared with non-acylated ^99mTc-plasmin. The observed uptake is less than that obtained with ¹²⁵I-fibrinogen at clinically useful time intervals post-injection but represents a significant advantage over the use of ^99mTc-plasmin.     

Fission Mo-99/Tc-99m generators —A study of their performance and quality

Five ^99mTc-generators, based on fission Mo-99, from five different manufacturers were studied in April and May of 1977 — with regard to their performance and to the quality of the eluates. The study covers types of generators not already dealt with in a previous publication [5].One generator was overloaded with Mo-99; one generator had Tc-99m yields below 70%. One generator yielded eluates containing appreciable -emitting impurities other than Mo-99. Two generators yielded eluates containing trace amounts of Al⁺⁺⁺.The content of - and pure -emitting nuclidic impurities (other than Tc-99) were in all cases below the limits set in the DLS 79 [2] monograph on Tc-99m pertechnetate obtained from fission Mo-99.     

Parametric imaging of regional cerebral blood flow with the short-lived isotope 195mAu

The use of the short-lived (30 s) isotope ^195mAu in brain perfusion studies has been tested on 40 patients and 8 volunteers. The activity of the eluate from the ^195mHg/¹⁹⁵Au generator was high enough to give good image statistics of brain perfusion after a single bolus injection. The examinations can be repeated after 3 min giving the same quality and without significant background. The use of a low-energy photon peak at 68 keV (Au–K) allows the imaging of brain perfusion in both lateral views with almost no look-through effect. With a modified height-over-area formula for the calculation of regional cerebral blood flow parametric images were obtained of high diagnostic value. The sensitivity and reproducibility, of the method has been demonstrated by mental stimulation tests on eight volunteers: after optical stimulation a clear increase of blood flow could be shown in the visual cortex.     

99mTc-DTPA gamma-camera renography: Normal values and rapid determination of single-kidney glomerular filtration rate

A method for ^99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, ^99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right-and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of ^99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of ^99mTc-DTPA. The coefficient of variation—a combination of inaccuracy and imprecision in the estimates as well as in the reference values — was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from ^99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

The stereoisomers of 17α-[123I]iodovinyloestradiol and its 11α-methoxy derivative evaluated for their oestrogen receptor binding in human MCF-7 cells and rat uterus,and their distribution in immature rats

We studied the potential of both stereoisomers of 17-[¹²³I]iodovinyloestradiol (E- andZ-[¹²³I]IVE) and of 11-methoxy-17-[¹²³I]iodovinyloestradiol (E-andZ-[¹²³I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[¹²³I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their¹²³I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[¹²³I]MIVE being higher than that ofE- andZ-[¹²³I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [¹²³I]MIVE. The uterus-to-blood uptake ratio was higher for^E-[¹²³I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [¹²³I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[¹²³I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted.