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

Seven 99Mo/99mTc generators (using fission 99Mo) obtained from seven different manufacturers 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 with 99Mo 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 of 99Mo breakthrough using a commercially available dose calibrator with a 99Mo assay shield indicated a misleadingly high 99Mo 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 microgram 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.     

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.     

A micro-autoradiographical study of the localization of 99mTc(Sn)-MDP and 99mTc-MDP in undecalcified bone sections

The localization of ^99mTc(Sn)-MDP in bone tissue was compared with ^99mTc-MDP by means of microautoradiography of undecalcified bone sections. Sections of good histological quality were obtained by a rapid embedding method in methylmethacrylate. No differences were found in the localization of these radiopharmaceuticals in fetal rat calvariae after incubation in vitro or in rat femora after administration in vivo. In the incubation experiment, hydrolyzed ^99mTc was formed. The uptake was high in areas of new bone formation. No uptake was seen in cells or in resorbing areas. In compact bone ^99mTc(Sn)-MDP was predominantly taken up in the vicinity of blood vessels.     

Isolation and labelling of human leukocytes with 99mTc

The role of the leukocyte isolation procedure on cell labelling with ^99mTc has been evaluated. Separation of leukocytes was performed by two procedures: (1) sedimentation on methyl cellulose, followed by discontinuous gradient centrifugation; (2) methyl cellulose sedimentation and hypotonic haemolysis of residual red blood cells. After washing the cells in saline and incubation with a stannous pyrophosphate agent, the leukocytes were labelled with 5–10 mCi ^99mTc. Procedure 1 gave a higher purity but lower recovery of polymorphonuclear leukocytes, and a minor contamination of red blood cells. ^99mTc labelling of cells was slightly more efficient with this method, probably due to the presence of red blood cells. Procedure 1 is recommended for in vitro studies on cell kinetics and procedure 2 is recommended for clinical use.     

Radiation dose to various age groups from radionuclide impurities in 99mTc-pertechnetate (Fission product 99Mo generator) radiopharmaceutical preparations

Radionuclide impurities of radiopharmaceuticals do not provide any diagnostic information, but contribute to the radiation dose to the patient. For ^99mTc, even small amounts of long lived radionuclide impurities may contribute significantly to the dose from ^99mTc itself. In this preliminary study, estimates have been made for the radiation dose to specific organs and for the effective dose equivalent from impurities in ^99mTc-sodium pertechnetate prepared from fission product ⁹⁹Mo. In addition to ⁹⁹Mo, ¹³¹I, ¹⁰³Ru, ⁸⁹Sr and ⁹⁰Sr at maximum permissible levels as stipulated in the European Pharmacopoeia, ^110mAg and ²³⁹Pu were taken as representative nuclides for beta-gamma emitters and alpha emitters. Using all of these radionuclides at such maximum permissible levels of impurity as stated in the European Pharmacopoeia, the total contribution from the impurities to the effective dose equivalent is approximately 30% of the effective dose equivalent from ^99mTc-pertechnetate. In terms of specific organs, the liver and kidneys can receive doses of 3–4 times and 1–3 times the dose from ^99mTc-pertechnetate itself. Although these are worst case calculations, a consistent approach should be reconsidered to limit the additional effective dose equivalent from impurities to e.g. 10% of the effective dose equivalent from ^99mTc itself.     

The use of the effective dose equivalent,H E,for 99mTc labelled radiopharmaceuticals

Using the concept of effective dose equivalent, H _E, it is shown that a knowledge of the detailed biodistribution data in most organs and tissues taking up ^99mTc labelled radiopharmaceuticals is unnecessary for the calculation of radiation risk. Reasonably precise dosimetry (±25%) can be obtained from urine excretion data alone providing there is no significant uptake within the gonads or the thyroid. Special attention should only be paid to absorbed dose measurements in red bone marrow, skin, lungs, gonads and thyroid, with the greatest attention directed toward the retention and dosimetric aspects of radioactivity in the latter two organs. An example H _E calculation for ^99mTc labelled d,1-HMPAO is presented to illustrate the importance of these specific five organs to radiation risk.     

Esophageal dischalasia: Serendipity during 99mTc thyroid scan

It is rare for a large amount of pooled radioactive saliva to be observed in the neck during a thyroid scan. Such a finding would imply abnormal salivation and/or esophageal kinesis. The case of esophageal dischalasia reported here suggests that a complete study of the esophagus is advisable when a large area or amount of radioactive saliva is observed in the neck during a thyroid scan.     

Dramatic intestinal uptake of99mTc pertechnetate in a pediatric patient with enteritis

A pediatric patient with enteritis, which showed dramatically diffuse uptake of 99mTc pertechnetate in the intestine, is reported. Repeated study after medical treatment exhibited complete disappearance of the intestinal uptake. 99mTc pertechnetate scintigraphy has the potentiality for diagnosing and monitoring active enteritis.     

Use of pertechnetate 99mTc for abdominal scanning in localising an ileal duplication cyst: case report and review of the literature

A 10-year-old boy presented with periumbilical postprandial pain and some melena. Physical examination was normal. All investigations were negative except a pertechnetate ^99mTc abdominal scan which showed a very large and horn-shaped focus of high activity in the right flank. An ileal duplication was resected. It was lined by antral gastric mucosa with a large ulcer. The patient was treated successfully. The abdominal pertechnetate scan is discussed. Offprint requests to: X. Marchandise     

Diffuse pulmonary uptake of 99mTc bone-imaging agents: Case report and survey

Over the past 5 years, we have encountered 6 cases of diffuse pulmonary uptake of ^99m-Tc bone-scanning agents (incidence, 0.04%). To assess the significance of this phenomenon, we reviewed all of the cases reported since 1974 (Including our series, a total of 32 cases). Three groups can be discerned, the first consisting of 24 patients without radiological calcifications in the lungs and with hypercalcemia of different origins (mostly hyperparathyroidism). Of the eight autopsies performed in this group, seven revealed extensive calcifications in alveolar walls and lung vessels; the other autopsy showed no calcification at all and only bronchopneumonic lesions. The second group consists of 6 patients in chronic dialysis. The last group consists of 2 patients having diffuse pulmonary alveolar microlithiasis with extensive radiologic calcifications.The mechanism of lung uptake of ^99m-Tc bone-imaging agents is probably the same as that of bone uptake (chemisorption on hydroxyapatite crystals), although other uptake mechanisms have also been discussed.Bone scintigraphy can be useful in the detection of early pulmonary calcifications, which have been associated with impaired pulmonary function and, due to their size, are generally not detected by X-ray.     

Semiquantitative assessment of regional cerebral perfusion using 99mTc HM-PAO and emission tomography

A method for the relative quantification of ^99mTc-HM-PAO distribution in brain SPECT is described. The method, applied in 12 normal volunteers and 150 patients suffering from different cerebral diseases, uses circumferential profiles to quantify the relative radionuclide distribution in the brain tomograms as an angular function with the origin at the center of the brain slice.Abnormal ^99mTc-HM-PAO distribution is evaluated by comparing the count content of symmetrical selected parts of the profile curve and comparing each patient's profile with the corresponding limits of normal ones, determined from the pooled profiles of 12 normal subjects.This computerized method allows an accurate, reproducible and objective assessment of the relative HM-PAO distribution in the brain.     

Animal and human studies of a new 99mTc labelled phosphine-isocyanide complex with possible applications to radionuclide ventriculography

A new ^99mTc-phosphine-isocyanide complex with the general structure [^99mTc (DEPE)₂ (CNR)₂]⁺ has been synthesised and tested in animals and one human. In three animal species (rat, rabbit, dog), the complex is an efficient myocardial imaging agent, while in humans it remains in the blood pool. The complex is 100% protein bound in animals and humans, but whereas in humans it is attached to a 51.5 kdalton protein (probably prealbumin), in rabbits it appears to be bound to a larger macromolecule (M.W.> 100 kdalton). The efficiency of the complex for blood pool labelling was tested in a human volunteer and compared with the standard in vivo red cell labelling technique with stannous pyrophosphate. A satisfactory radionuclide angiogram could be performed with less than 370 MBq of the complex. The count rate for the complex (cps/MBq) was 15% higher than that obtained with the labelled red cells and the absence of splenic activity was notable. In humans this complex appears to be an efficient blood pool labelling agent which might be useful for radionuclide ventriculography.     

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.     

Clinical evaluation of 99mTc(V)-dimercapto succinic acid (DMSA) for imaging medullary carcinoma of thyroid and its metastasis

^99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12(80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of ^99mTc (V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of ^99mTc (V)-DMSA (64.9%). In addition, ^99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of ^99mTc (V)-DMSA concentration in soft tissue and bone metastasis was similar.Isopharm, Radiopharmaceutical Division, BARC, Bombay-400 705, India     

The use of human albumin millimicrospheres tagged with 99mTc in the evaluation of the removal capacity of the reticuloendothelial system

Liver uptake kinetics of ^99mTc labelled millimicrospheres of human serum albumin (MM) was studied in 16 subjects. Every subject received four doses of MM intravenously. The uptake constant decreased progressively with increasing dose. The maximum liver removal capacity, a parameter which is independent of liver blood flow, was calculated according to the method of Iio and Wagner (1963). From these data we conclude that MM are taken up by the reticuloendothelial system (RES) with saturable kinetics, and they are suitable for clinical use to evaluate RES function in man.     

Scintigraphic localization of occult gastrointestinal bleeding using a combination of 111In-labelled platelets and 99mTc sulphur colloid

Repeated scintigraphy was performed for 6 days after the injection of autologous ¹¹¹In-labelled platelets in a patient showing signs of recurrent occult gastrointestinal bleeding. Colonic activity was observed 142 h post injection, at which time a superimposed study using ^99mTc sulphur colloid pinpointed the source of bleeding in the transverse colon.     

Preparation and evaluation of 99mTc(V)-DMSA complex: Studies in medullary carcinoma of thyroid

Consequent to the promising results reported with ^99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways:-(i) from freshly prepared reagents, (ii) through the use of a two component kit and (iii) use of the standard renal DMSA kit by a modified recipe. The ^99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

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     

An electrochemical procedure to concentrate Tc availed from a zirconium [Mo] molybdate gel generator

Successful use of electrochemical method to concentrate ^99mTc obtained from a zirconium molybdate (Zr⁹⁹Mo) gel generator is reported. The process consists of electrodeposition of the ^99mTc in an oxalate bath on a small platinum electrode followed by recovery of ^99mTc in a small volume of normal saline. The overall recovery of ^99mTc was >90% with >99.99% radionuclidic purity and >99% radiochemical purity. The compatibility of the product in the preparation of ^99mTc labeled formulations such as ^99mTc-DMSA and ^99mTc-EC was found to be satisfactory in terms of high labeling yields (>98%).     

The role of radionuclide lymphoscintigraphy in extremity lymphedema

The characteristics of lymphedema on radionuclide lymphoscintigraphy were studied, and the diagnostic value of radionuclide lymphoscintigraphy in lymphedema was evaluated. In this report radionuclide lymphoscintigraphy was performed in 110 cases of clinically suspected lymphedema. A retrospective study method was used to analyze the imaging results. The typical pattern of lymphedema on radionuclide lymphoscintigraphy was summarized. It was found that the characteristics of lymphedema on radionuclide lymphoscintigraphy were diverse. The most common pattern was increased radiotracer accumulation in the soft tissue and lymphatic webs. Surgery and infection dominated as the causes of lymphedema in this study. It was concluded that radionuclide lymphoscintigraphy is a useful noninvasive method for diagnosing lymphedema. It is easy to operate and provides reliable results.