99mTc-Diethyl-iodo-HIDA (JODIDA): A new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, ^99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with ^99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 mol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.     

81mKr equilibrium radionuclide ventriculography for the assessment of right heart function

Right heart^81mKr equilibrium radionuclide ventriculography was used to derive right ventricular ejection fraction (RVEF) in 12 healthy male volunteers. Anatomical lung subtraction using^99mTc-MAA perfusion scintigraphy was compared with conventional background correction and the effect of imaging projection on the techniques of image analysis evaluated. Both intra and inter observer variability were reduced by anatomical lung subtraction when compared to conventional background correction. In the right anterior oblique (RAO) projection, background corrected RVEF was lower than lung subtracted RVEF - 0.544 ±0.05 and 0.612±0.08 (mean ± SD) (P<0.02). Lung subtracted RVEF in the anterior projection was lower than that with background correction (P<0.05) and lower than lung subtracted RVEF in the RAO projection (P < 0.001). We conclude that optimal separation of right heart structures is achieved in the RAO projection and that reproducibility of the analytical technique is improved by anatomical lung subtraction.     

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.

     

Scintimammography with 99mTc-MIBI and magnetic resonance imaging in the evaluation of breast cancer

This study was performed to evaluate the sensitivity and specificity of technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) scintimammography (SMM) and contrast-enhanced magnetic resonance imaging (MRI) in patients with breast masses, using the histological findings as the gold standard. Forty-five consecutive patients with a breast lesion, detected by self-examination, physical examination or screening mammography, underwent SMM and MRI. In 38 cases (84.5%), the histopathology was malignant; the breast cancers ranged from 3 to 100 mm in diameter (mean 22 mm). In the overall patient group, MRI showed a slightly higher sensitivity than SMM (92% vs 84%), but SMM showed a better specificity: 71% vs 42%. The accuracy was 82% and 84% for SMM and MRI respectively. To evaluate the influence of lesion size on the results, patients with lesions 20 mm and 15 mm were examined. In patients with lesions 20 mm, the sensitivity of SMM and MRI decreased to 64% and 82% respectively, while SMM again displayed considerably better specificity: 83% vs 50% for MRI. The accuracy of SMM and MRI was 64% and 82% respectively. In patients with lesions 15 mm, SMM again showed better specificity (75% vs 50%), while MRI displayed better sensitivity and accuracy (sensitivity, 81% vs 62%; accuracy, 75% vs 65%). In this study the specificity of SMM in patients with breast lesions was thus superior to that of MRI. The combination of SMM and MRI may be used in those patients with equivocal findings at mammography and ultrasound to reduce the number of unnecessary surgical biopsies.     

Clinical relevance of imaging proliferative activity in lung nodules

Purpose Recently, the thymidine analogue 3-deoxy-3[¹⁸F]fluorothymidine (FLT) has been introduced for imaging proliferation with positron emission tomography (PET). In this prospective study, we examined the accuracy of FLT for differentiation of benign from malignant lung lesions and for tumour staging.Methods A total of 47 patients with newly diagnosed pulmonary nodules on chest CT suspicious for malignancy were examined with FLT-PET in addition to routine staging procedures. A total of 43 patients also underwent 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) PET imaging. Within 2 weeks, patients underwent resective surgery or core biopsy of the pulmonary lesion.Results Histopathology revealed malignant lung tumours in 32 patients (20 non-small cell lung cancer, 1 small cell lung cancer, 1 pulmonary carcinoid, 1 non-Hodgkins lymphoma, nine metastases from extrapulmonary tumours) and benign lesions in 15 patients. Increased FLT uptake was exclusively related to malignant tumours. FLT-PET was false negative in two patients with non-small cell lung cancer, in the patient with a pulmonary carcinoid and in three patients with lung metastases. The sensitivity of FLT-PET for detection of lung cancer was 90%, the specificity 100% and the accuracy 94%. Fifteen out of 21 patients with lung cancer had mediastinal lymph node metastases. FLT-PET was true positive in 7/15 patients, resulting in a sensitivity of 53% for N-staging (specificity 100%, accuracy 67%). Clinical TNM stage was correctly identified in 67% (20/30) patients, compared to 85% (23/27) with FDG-PET.Conclusion FLT-PET has a high specificity for the detection of malignant lung tumours. Compared with FDG, FLT-PET is less accurate for N-staging in patients with lung cancer and for detection of lung metastases. FLT-PET therefore cannot be recommended for staging of lung cancer.     

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.     

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 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 everage pixel values for ventilation and perfusion. Results in a group of eight healthy volunteers are described and discussed.     

Radiopharmacokinetics and radiation dose from 99mTc-HM-PAO (Preliminary report)

Whole body retention measurements were performed in volunteers after i.v. injection of ^99mTc-HM-PAO (Ceretec^®). The organ accumulation was measured in mice and data were transferred to standard man according to ICRP. Absorbed dose calculations were made with these data by using the concept of absorbed fractions (MIRD method). In man, the whole body retention and the retention in the brain could be calculated by direct measurement, absorbed doses to the other organs could only be derived from animal data. The absorbed dose to the brain derived from human data (10.3 Gy/MBq) is greater by a factor of 2 than that derived from animal data. The highest absorbed dose was received by the thyroid (24.4 Gy/MBq), the absorbed dose to the ovaries, testes and whole body ranged from 2.8 to 4.2 Gy/MBq.Dedicated to Professor Dr. Guenter Liess on the occasion of his 65th anniversary     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with ^99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free ^99mTcO ₄ ^- was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200–600 Ci/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample, was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed, and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12%±0.77% to 4.28%±1.57% at 3 and 2 h, respectively (P<0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that ^99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

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.     

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.     

Application of I-123 HIPDM as a lung imaging agent

N,N,N-Trimethyl-N-(2-Hydroxyl-3-Methyl-5-¹²³I Iodobenzyl)-1,3-Propanediamine · Hcl (¹²³I-HIPDM) has been used for diagnosis of patients with strokes and dementias. Since this radiopharmaceutical is also accumulated in the lung, we routinely performed a lung image or images immediately prior to cerebral planar and SPECT images after a 3–5 mCi ¹²³I-HIPDM injection. During the past 14 months, we obtained 78 (age from 41 to 92 years, average 66.7±8.9 years; 64 males, 14 females) suspected stroke or dementia patients' lung images. All lung images were correlated to chest X-ray (CXR) or CT and other clinical data. Sixty five of 78 patients had normal lungs showing homogeneous distribution of activity throughout the lungs which correlated well to normal CXR and/or CT studies. Abnormal scintigraphic patterns of the 13 patients included lung defect (5 bronchogenic carcinoma with or without atelectasis) and decreased uptake in apices (8 chronic obstructive pulmonary disease). The findings of pulmonary intrathoracic pathologies on lung images with ¹²³I-HIPDM suggests further evaluation of the agent for detection of localized pulmonary diseases and pulmonary physiological studies relating to amine metabolism.This investigation was supported in part by Biomedical Research Support Grant no. RR05374 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, NIH     

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.     

Finding an optimal method for imaging lymphatic vessels of the upper limb

Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with ^99mTc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id ^99mTc-HIG was compared with sc ^99mTc-HIG, in three id ^99mTc-nanocolloid was compared with sc ^99mTc-nanocolloid, in three id ^99mTc-HIG was compared with id ^99mTc-nanocolloid and in three sc ^99mTc-HIG was compared with sc ^99mTc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance (k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, ^99mTc-HIG gave images that were marginally but significantly better than those given by ^99mTc-nanocolloid. Image quality correlated inversely with time after injection at which the best image was obtained, consistent with the notion that good vessel definition was dependent on a narrow bolus width. k was approximately three times higher after id injection than after sc injection but it was not significantly different between radiopharmaceuticals for either injection route. Intradermal ^99mTc-HIG gave a cardiac blood pool signal that, over the first 60 min, increased about five times faster than that with sc ^99mTc-HIG, but no clear difference was observed in the rate of increase in hepatic activity between id ^99mTc-nanocolloid and sc ^99mTc-nanocolloid. We conclude that id injection provides rapid access of radiotracers to lymphatic vessels, which is ideal for imaging lymphatic vessel morphology. ^99mTc-HIG is marginally superior to nanocolloid for this purpose and, in drainage basins from which lymph nodes have been excised, is not handicapped by a potentially inferior ability, compared with radiocolloid, to image lymph nodes.     

The Clinical Usefulness of 99mTc HMPAO Leukocyte/99mTc Phytate Bone Marrow Scintigraphy for Diagnosis of Prosthetic Knee Infection: A Preliminary Study

Purpose

The preferred radionuclide imaging procedure for diagnosing prosthetic joint infection is combined radiolabeled leukocyte/^99mTc sulfur colloid bone marrow scintigraphy, which has an accuracy of over 90 %. Unfortunately, sulfur colloid is no longer available in South Korea. In this study, we evaluated the usefulness of ^99mTc phytate, a substitute for ^99mTc sulfur colloid, when combined with radiolabeled leukocyte scintigraphy in suspected prosthetic knee infections.

Methods

Eleven patients (nine women, two men; mean age 72 ± 6 years) with painful knee prostheses and a suspicion of infection underwent both ^99mTc HMPAO leukocyte scintigraphy (LS) and ^99mTc phytate bone marrow scintigraphy (BMS). The combined images were interpreted as positive for infection when radioactivity in the LS at the site of clinical interest clearly exceeded that of the BMS (discordant); they were interpreted as negative when the increased activity in the LS was consistent with an increased activity in the BMS (concordant). The final diagnosis was made with microbiological or intraoperative findings and a clinical follow-up of at least 12 months.

Results

Five of eleven patients were diagnosed as having an infected prosthesis. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the combined LS/BMS were 100 %, 83 %, 83 %, 100 % and 91 %, respectively.

Conclusion

We find that combined ^99mTc HMPAO LS/^99mTc phytate BMS shows comparable diagnostic performance to other studies utilizing sulfur colloid. Combined ^99mTc HMPAO LS/^99mTc phytate BMS is therefore expected to be an acceptable alternative to combined radiolabeled LS/^99mTc sulfur colloid BMS for diagnosing prosthetic knee infections.     

Two-dimensional and three-dimensional oxygen mapping by 3He-MRI validation in a lung phantom

The aim of this study was to validate oxygen-sensitive ³He-MRI in noninvasive determination of the regional, two- and three-dimensional distribution of oxygen partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung phantom, oxygen sensitive two- and three-dimensional ³He-MRI measurements were performed at different oxygen concentrations which had been equilibrated in a range of normal and pathologic values. The oxygen partial pressure distribution was determined from ³He-MRI using newly developed software allowing for mapping of oxygen partial pressure. The reference bulk oxygen partial pressure inside the phantom was measured by conventional respiratory gas analysis. In two-dimensional measurements, image-based and gas-analysis results correlated with r=0.98; in three-dimensional measurements the between-methods correlation coefficient was r=0.89. The signal-to-noise ratio of three-dimensional measurements was about half of that of two-dimensional measurements and became critical (below 3) in some data sets. Oxygen-sensitive ³He-MRI allows for noninvasive determination of the two- and three-dimensional distribution of oxygen partial pressure in gas-filled airspaces.     

Prospective dosimetry with <Superscript>99m</Superscript>Tc-MDP in metabolic radiotherapy of bone metastases with <Superscript>153</Superscript>Sm-EDTMP

Purpose

On the basis of the encouraging results achieved in several clinical trials and its proven therapeutic efficacy, ¹⁵³Sm-ethylene diamine tetramethylene phosphonic acid (EDTMP) has become widely used to palliate pain from bone metastases. The results reported in the literature have led the product suppliers (QUADRAMET®, Schering) to suggest administering a fixed activity per kilogram (37 MBq/kg). However, considering the observed extreme inter-patient variability of skeletal uptake of ¹⁵³Sm-EDTMP, a real therapy optimization would require the individualization of the activity to be administered on a dosimetric basis. This should be planned taking into account the generally accepted 2-Gy dose constraint to the haematopoietic red marrow, the critical organ in palliative treatments with beta-emitting, bone-seeking radiopharmaceuticals.

Methods

Seven to 14 days before treatment with ¹⁵³Sm-EDTMP, 44 patients underwent ^99mTc-methylene diphosphonate (MDP) total-body bone scan with two scans (the first within 10 min of injection, the second after 6 h). The percentage bone uptake (Tc_%) was evaluated as the ratio between total counts at 6 h, adjusted for decay, and total counts at the first scan. Tc_% was then compared to Sm_% similarly derived from 10-min and 24-h whole-body scans. Tc_% and Sm_% were compared both with and without Brenner’s method for soft tissue uptake.

Results

The correlation between Tc_% and Sm_% was R ²?=?0.81 and R ²?=?0.88 with and without soft tissue correction, respectively. The difference between their average values was statistically significant (Sm_%?=?64.3?±?15.2, Tc_%?=?56.2?±?16.0; p?=?0.017) with soft tissue correction, while was not statistically significant (Sm_%?=?68.2?±?15.5, Tc_%?=?66.9?±?14.0; p?=?0.670) without soft tissue correction.

Conclusions

The rate of retention of ^99mTc-MDP in bone provides a reliable estimate of the ¹⁵³Sm-EDTMP rate of retention. The proposed method can be usefully adopted for prospective dosimetry seeing its extreme simplicity, and it requires no special investment in terms of human or instrumental resources. This allows an optimization of administered ¹⁵³Sm-EDTMP activity.

     

Chemical,radiochemical, and radionuclide purity of eluates from different commercial fission99Mo/99mTc generators

Seven⁹⁹Mo/^99mTc generators (using fission⁹⁹Mo) obtained from seven different manufactures were studied in 1984 and 1985 to test the quality of the eluates. We present the findings concerning the elution efficiency, radionuclide purity,⁹⁹Mo breakthrough, radiochemical purity, pH, and aluminium content of the eluates. One generator was overloaded with⁹⁹Mo by about 40%, while one generator had^99mTc yields of only about 80%. The eluates generally (although with some exceptions) exhibited a high and satisfactory radionuclidic purity and good radiochemical purity. The low-level determination of⁹⁹Mo break-through using a commercially available dose calibrator with a⁹⁹Mo assay shiled indicated a misleadingly high⁹⁹Mo content. All of the eluates had pH values of between 5.0 and 5.5, and the aluminium content was always below the detection limit of 1 g per milliliter of eluate. The generators performed well and proved their capability of functioning as reliable sources of sodium pertechnetate Tc99m. In all cases, the pertechnetate produced met the requirements of the European Pharmacopeia.This report is based on work conducted within the scope of a research poject devised by the Ministry of the Interior of the Federal Republic of Germany (Hammermaier et al. 1985). The present report reflects the opinions of the authors and does not necessarily express the views of the Federal Ministry of the Interior     

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.     

Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low kidney uptake

We have recently shown that accumulation in mouse kidneys of technetium-99m labeled phosphorodiamidate morpholinos (MORFs) increases with the number of cytosines in the base sequence. To improve tumor/kidney ratios in tumored mice, pretargeting studies were performed with a cytosine-free MORF. An 18-mer MORF (5-TCTTCTACTTCACAACTA) was conjugated to the anti-CEA antibody MN14 (Immunomedics) and administered to nude mice bearing LS174T tumors. Thereafter, the ^99mTc-labeled cytosine-free cMORF (5-TAGTTGTGAAGTAGAAGA-amide-MAG₃) was administered. For comparison, the identical study was repeated but with our original pair of 18-mer MORFs (5-GGGTGTACGTCACAACTA-conjugated MN14 and ^99mTc-labeled 5-TAGTTGTGACGTACACCC-amide-MAG₃). Surface plasmon resonance was used to show that the hybridization affinities of the original and the modified pair of MORFs were essentially equal. Hybridization of the cytosine-free cMORF-^99mTc to MN14-MORF was demonstrated in vitro by size-exclusion high-performance liquid chromatography. At 3 h, kidney levels in normal mice were 2.0%ID/organ for the modified cMORF vs. 4.1%ID/organ for the original cMORF sequence, while at 24 h, these values were 0.9% vs 1.8%ID/organ. Pretargeting studies in tumored mice receiving 25 g of conjugated antibody, 0.5 g of labeled cMORF 48 h later, followed by imaging and sacrifice at 3 h showed that kidney levels were reduced using the cytosine-free cMORF. Moreover, tumor accumulation was about 3.6%ID/g and was independent of sequence. The whole-body images clearly reflected the improved tumor to kidney ratios. By choosing a cytosine-free base sequence for pretargeting studies, kidney accumulation of cMORF-^99mTc was reduced without adversely influencing tumor accumulation. The lowering of kidney radioactivity levels in this way may be important to reduce toxicity to this organ in connection with pretargeting radiotherapy studies.