The use of a computer in ventilation-perfusion scintigraphy with Tc-99m macroaggregates and Kr-81m, to obtain a physiological model

In this article we describe a computer program to demonstrate ventilation-perfusion relationships in the lungs, using 99mTc-MAA and 81mKr, with the patients sitting upright, the normal physiological situation. The ventilation and perfusion scans are performed simultaneously with both gamma camera and computer adjusted for dual isotope mode. Steady state images are acquired in the frontal, dorsal, and left and right posterior oblique positions. Additionally, in the dorsal and frontal projections, a sequence of 12 washout images (5 s) is registered, after closing the Krypton supply. After normalization and further computer processing, the following parameters are calculated in the frontal and dorsal projections, in the whole lung and in four horizontal subregions: washout values, ventilation-perfusion ratios, left to right ratios of ventilation and perfusion, and left to right ratios of the average pixel values for ventilation and perfusion. Results in a group of eight healthy volunteers are described and discussed.     

Right ventricular ejection fraction: Comparison of technetium-99m first pass technique and ECG-gated steady state krypton-81m angiocardiography

Right ventricular ejection fraction (RVEF) calculated from ECG-gated steady-state ^81mKr angiocardiography and from ^99mTc first-pass studies were compared in 30 patients using a digital, single crystal, gamma-camera. Despite the two entirely different approaches RVEF values obtained by the two methods were comparable (r=0.97): the mean absolute difference between the two techniques was 2.5%+/-1.5% and the largest observed absolute difference was 5%. In the absence of an accepted reference method for measuring RVEF, this close correlation provides indirect validation of both techniques. The choice of method will therefore depend on several factors, including radiotracer availability, the characteristics of the gammacamera and the protocol of clinical investigation.     

Osteoid osteoma simulating osteomyelitis: Differentiation with Tc-99m HIG scintigraphy

We present a case of osteoid osteoma with a history of mild pain, local swelling and point tenderness on the right lower leg. The diagnosis of osteoid osteoma was difficult due to the atypical clinical history and misleading radiological and bone scan findings. When it is difficult to differentiate an osteoid osteoma from osteomyelitis using CT, MRI or bone scan; HIG scintigraphy can be used to exclude an infection.     

Dynamic isotopic phlebography using soluble krypton-81m

Intravenous peripheral injection of krypton-81m in an isotonic solution permits venous scintigraphy of the lower limbs to be carried out. An anatomic definition of the obstructions and the collateral pathways is therefore easily displayed from the popliteal vein to the vena cava. The physical characteristics of the radionuclide permit iterative or sustained perfusions without accumulation of an excessive background noise and the method is used to obtain scintigraphic images in changing physiological conditions. Analysis of the dynamic data permits venous stasis to be assessed in terms of regional radioactivity at a steady state and transit rate. Various physiological and pathological conditions are analyzed by this method.     

Mismatch between99mTc-DTPA aerosol and81mKr lung ventilation scintigraphy: a pitfall of radionuclide imaging

Pulmonary ventilation and perfusion scintigraphies were performed using^99mTc-MAA,^81mKr, and^99mTc-DTPA aerosol in a patient with asthma. Lung perfusion scintigraphy and^99mTc-DTPA aerosol scintigraphy showed multiple matching defects, however,^81mKr ventilation scintigraphy showed mismatch with lung perfusion scintigraphy. A pitfall of this examination was discussed.     

Kinetics of Tc-99m hexakis t-butyl isonitrile in normal and ischemic canine myocardium

Hexakis ^99mTc-tertiary butyl isonitrile (^99mTc-TBI) was studied as a cardiac perfusion imaging agent in nine dogs with partial occlusion of the LAD. Thirty min after applying the stenosis, ^99mTc-TBI was injected into the right atrium (RA) in five dogs and left atrium (LA) in four dogs. Normal and ischemic zone regional myocardial ^99mTc-TBI activites were monitored continuously for 4 h. Dogs with LA injections had minimal and equivalent 4 h fractional clearance from the normal and ischemic zones. Dogs with RA injections had minimal, but significantly lower 4 h fractional ^99mTc clearances in the ischemic zone (0.08±0.08) compared to the normal zone (0.16±0.07, P<0.05). The delayed ischemic zone clearance is probably due to the high initial lung uptake observed after RA injection. Despite the differences in clearance, this minimal amount of redistribution could not be detected on gamma camera images. The minimal myocardial washout and redistribution, and the 140 keV gamma make ^99mTc-TBI a promising cardiac perfusion imaging agent.Dr. Okada is an Established Investigator of the American Heart Association     

A breathing lung phantom for 81mKr lung ventilation studies its use in dosimetry and quality control

The construction of a breathing lung phantom that can be used to measure the amount of radioactive gas in the lungs as well as to determine the absorbed dose is described. For a lung ventilation study that consists of 6 views of 300 kents each, an effective dose equivalent of 50 Sv was calculated. The phantom is also suitable for comparison of different generator systems.     

A study on attenuation correction using Tc-99m external TCT source in Tc-99m GSA liver SPECT

PURPOSE: In attenuation correction of ECT images by transmission CT (TCT) with an external 99mTc gamma-ray source, simultaneous TCT/ECT data acquisition is difficult, when the same radionuclide such as 99mTc-tetrofosmin or 99mTc-GSA is used as the tracer. In this case, TCT is usually acquired before administration of the tracer, and ECT is acquired separately after the tracer injection. However, misregistration may occur between the TCT and ECT images, and the repetition of examinations add to the mental and physical stress of the patients. In this study, to eliminate this problem, we evaluated whether attenuation correction of ECT images can be achieved by acquiring TCT and ECT simultaneously, then acquiring ECT alone, and preparing an attenuation map by subtracting the latter from the former using 99mTc-GSA liver ECT. METHOD: The ECT system used was a three-head gamma camera equipped with one cardiac fan beam collimator and two parallel beam collimators. External gamma-ray source for TCT of 99mTc was 740 MBq, and ECT of 99mTc-GSA was 185 MBq. First, pure TCT data were acquired for the original TCT-map, then, ECT/TCT data were acquired for the subtracted TCT-map, and finally, pure ECT data were acquired. The subtracted attenuation map was produced by subtracting the pure ECT image from the TCT/ECT image, and attenuation correction of the ECT image was done using both this subtracted TCT map and attenuation map from pure TCT. These two attenuation corrected images and non-corrected images were compared. Hot rods phantom, a liver phantom with a defect, and 10 patients were evaluated. RESULTS: Attenuation corrected ECT values using the subtraction attenuation map showed an error of about 5% underestimation compared with ECT values of the images corrected by original attenuation map at the defect in the liver phantom. A good correlation of y = 22.65 + 1.06x, r = 0.958 was observed also in clinical evaluation. CONCLUSION: By means of the method proposed in this study, it is possible to perform simultaneous TCT/ECT data acquisition for attenuation correction using Tc-99m external source in Tc-99m GSA liver SPECT. Moreover, it is thought that this method decreases the mental and physical stress of the patients.     

Technetium-99m mercaptoalbumin as a potential substitute for technetium-99m labelled red blood cells

Technetium-99m labelled red blood cells (^99mTc-RBCs) are far superior to ^99mTc-labelled human serum albumin (^99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical ^99mTc-mercaptoalbumin with long retention in the vascular system, that could replace ^99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with ^99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure ^99mTc-mercaptoalbumin. Stable ^99mTc-mercaptoalbumin complexes could be formed in 90%–95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25: 1 ratio and deprotection with NH₂OH. The stability of the resulting ^99mTc-mercaptoacetyl-albumin (^99mTc-MAHSA) and ^99mTc-dimercaptopropionyl-albumin (^99mTcDMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional ^99mTc-HSA preparations. ^99mTc-DMP-HSA approaches the behaviour of ¹²⁵I-HSA quite well in both animal species. A preliminary study with ^99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of ^99mTc-RBCs and clearly higher than that of a common ^99mTc-HSA preparation. The results indicate that these ^99mTc-mercaptoalbumins and especially ^99mTc-DMP-HSA are very promising as a practical alternative to ^99mTc-RBCs.K.A. Verbeke is a Research Assistant for the Belgian National Fund for Scientific Research     

The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to ^99mTc-methylene biphosphonate (^99mTc-MDP) in normal rabbits. Preparation of 0.50 mg of ^99mTc-ZOL was carried out by the reduction of ^99mTc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. ^99mTc-ZOL and ^99mTc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between ^99mTc-ZOL and ^99mTc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of ^99mTc-MDP were higher than ^99mTc-ZOL at the static studies.     

99mTc-DTPA and 99mTc-rhenium sulfur aerosol compared as adjuncts to perfusion scintigraphy in patients with suspected pulmonary embolism

Two radiopharmaceuticals, ^99mTc-DTPA (D) and ^99mTc-rhenium sulfur (R) were evaluated with a nebulizer delivering submicronic particles. Seventy-seven patients were examined (42 D, 35 R). For all patients, the examination began with a ventilation study. Immediately after the last ventilation view, ^99mTc MAA was injected. Aerosol performance was assessed in 37 D and 17 R. Nebulization yield was 8.98% for D and 9.31% for R. A lung clearance study was performed in 12 patients for D and in 12 different patients for R. The lung clearance was 0.22%/min for R and 2.35%/min for D. The quality of ventilation and the quantification of bronchial and gastric activity were evaluated; the difference between the two groups was not statistically significant. It may be concluded that radioaerosols allow good quality images to be obtained. The yield of the nebulizer is adequate, so that nebulization of 20 mCi delivers approximately 2 mCi of aerosol activity to the lung. When pulmonary embolism is being investigated, R, due to its slower lung clearance, would appear to be preferable to D for patients suspected of increased bronchoalveolar permeability, especially if the time between nebulization and recording is greater than 10 min.     

Clinical approach to renal study incidental to99mTc-MDP bone scintigraphy

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.     

Use of iodine-123 metaiodobenzylguanidine scintigraphy for the detection of amiodarone induced pulmonary toxicity in a rabbit model: A comparative study with technetium-99m diethyltriaminepenta acetic acid radioaerosol scintigraphy

The purpose of the study was; (i) to determine whether 123I-MIBG scintigraphy is sensitive for detection of amiodarone induced pulmonary toxicity (AIPT) and (ii) to compare it with 99mTc-DTPA radioaerosol. Twelve white New Zealand rabbit with initial mean body weight 4.24 +/- 0.47 g were divided into two groups. AIPT group (n = 7) was administered amiodarone (20 mg/kg BW). The control group (n = 5) received the same amount of 0.9% saline. All animals underwent 123I-MIBG and 99mTc-DTPA radioaerosol scintigraphy at the end of the treatment period. 123I-MIBG static thorax images were obtained during 10 minutes at 15 minutes and 3-hours after intravenous injection of the radiopharmaceutical. Lung to heart ratios (LHR) and lung to mediastinum ratios (LMR), and retention index (LRI) of 123I-MIBG were determined. Two days after 123I-MIBG scintigraphy, 99mTc-DTPA radioaerosol scintigraphy was performed, and clearance from the lungs was measured for 10 min (1 min/frame) following termination of inhalation. 123I-MIBG lung retention index (LRI) was significantly higher in the AIPT group than the control (61 +/- 4.6 vs. 40 +/- 4.5, p = 0.01). Early LHR and LMR were significantly lower in the AIPT group than in the control group (p = 0.04, p = 0.01, respectively), whereas those of late LHR and LMR were not significantly different. T1/2 values of DTPA clearance were significantly increased in AIPT group according to the control group (55 +/- 7.2 vs. 86.6 +/- 18.5, p = 0.02). 123I-MIBG scintigraphy is a valuable tool for detecting AIPT in a rabbit model. Additionally, 99mTc-DTPA radioaerosol scintigraphy is an excellent comprehensive investigational tool for detecting AIPT with the added advantage of lower cost.     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

Secondary lymphoma of the thyroid in 99mTc-pertechnetate scintigraphy

We present markedly decreased radioactivity in the right on a ^99mTc-pertechnetate thyroid image in a patient with secondary lymphoma of the thyroid. At autopsy, the right lobe of the thyroid was replaced by lymphoma tissue. Markedly decreased radioactivity on the images may be explained by lymphoma cell infiltration or replacement of thyroid tissue with a resultant attenuation effect as well as interference of the trapping mechanism of the thyroid folicular cell. While cold areas in a radionuclide scintigram may present difficulties in interpretation, a high index of secondary lymphoma suspicion should be made by a combination of the scintigraphic findings and history of malignant lymphoma.Supported in part by Biomedical Research support Grant No. RR 05374 from Biomedical Research Support Branch, Division of Research Facilities and Resources, NIH     

Tc-99m labeled triethelene tetraamine polysterene resin gastric emptying studies in bulimia patients

To evaluate gastric emptying in patients with bulimia, 20 patients (all women, ranging in age from 12 to 49 years) with upper gastrointestinal symptoms ingested 150–200 Ci ^99mTc-triethelene tetraamine polysterene resin in cereal and had scintigraphy in the supine position. Data were accumulated at 5 min intervals to determine the gastric emptying time (GET). The results showed that the gastric emptying time was prolonged in 12 patients and decreased in 8. All 12 patients with prolonged emptying time were given 10 mg metoclopramide intravenously; 9 of these had a good response and 3 had no response. Although all patients had subjective symptoms of gastric dysfunction, the results indicate that about 60% had delayed and 40% had rapid gastric emptying. The findings of two extremes of gastric emptying time remain to be explained, however, this enables (a) objective documentation of gastric emptying as this technique (b) can separate those patients with rapid GET from those with prolonged GET, who might benefit from metoclopramide.Supported in part by BRSG Grant RR # 05374 from the Biochemical Research Support Branch, Division of Research Facilities and Resources, NIH     

Gastrointestinal scintigraphy with 99mTc-DTPA labeled tablets in fed and fasting subjects

The in vitro and in vivo dissolution of a sustained release theophylline formulation labeled with ^99mTc-diethyltriaminepentaacetic acid (DTPA) has been monitored in six subjects with a scintillation camera. The study was performed in fasting conditions and was repeated after ingestion of a standardized meal. Results showed that the presence of food in the stomach dramatically increased the oesoduodenal transit time of the tablet (74±27 min vs 352±77 min, P<0.001) but did not modify the biodisponibility of theophylline. This study is another example when scintigraphy can be of definite value in pharmacokinetics.     

The stability of 99mTc-DTPA and 99mTc-HIDA following ultrasonic nebulisation

The stability of ^99mTc-DTPA (diethylenetriamine-pentaacetic acid) and ^99mTc-HIDA (2,6-diethylacetanilidoiminodiacetic acid) were evaluated following ultrasonic nebulisation. The results confirm that either of these radiopharmaceuticals can be used in our nebuliser without significant radiochemical breakdown.     

Initial experience with Tc-99m-HM-PAO in the study of brain tumors

A preliminary study of the distribution of the ^99mTc complex of hexamethylpropylene amine oxime (HM-PAO) in 12 patients with brain neoplasms before, during, and after radiotherapy has been performed. Untreated brain tumors were found to exhibit a range of ^99mTc-HM-PAO uptake, varying from areas of markedly increased isotope activity to photopenic areas, when compared to normal brain tissue. A ratio of ^99mTc-HM-PAO tumor uptake to contralateral normal tissue uptake was calculated prior to and during radiotherapy. This ratio tended to return towards unity in lesions responding to therapy. A predictable alteration in whole brain ^99mTc-HM-PAO uptake during radiotherapy was not demonstrated. Unlike the radiolabeled amines, ^99mTc-HM-PAO localizes in primary tumors, probably indicating that its uptake mechanism is independent of non specific amine receptors. ^99mTc-HM-PAO may be useful in the study of brain tumor physiology and response to therapy.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of^99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of^99mTc-plasmin, gallium citrate Ga 67,¹²⁵I-fibrinogen, and^99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor^99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of⁶⁷Ga,¹²⁵I-fibrinogen, or^99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed^99mTc-phasmin and¹²⁵I-fibrinogen to have the best localization characteristics.