MIRD Dose Estimate Report No. 14: radiation absorbed dose from technetium-99m-labeled red blood cells.
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Erythrocytes↗
Biomedical subjects
L R Chervu
Publications and source records attributed to L R Chervu.
Technetium-99m labeled p-aminohippuric acid analogues: renal function agents.
A number of p-aminohippuric acid analogues were synthesized in order to develop clinically useful 99mTc-labeled radiopharmaceuticals for evaluation of renal function measurements. Stable 99mTc-labeled complexes were formed at pH 5.7 using a Sn(II) reduction method with all derivatives. The newly synthesized complexes were screened utilizing biodistribution studies in small animals. All complexes were excreted via the GU tract within 60 min post iv administration, with no significant activity in GI tract and liver. The [99mTc]methyl-PAHIDA complex showed optimal biodistribution among these analogues. Further investigation is needed to determine if these derivatives may be used to replace [131I]o-iodohippuric acid for the evaluation of renal function.
Aminohippuric Acids↗
Iodine-131 MIBG scintigraphy in small cell lung cancer.
There is a well documented relationship between small cell carcinoma of the lung and the amine precursor uptake and decarboxylation system of endocrine cells (APUD). We attempted to exploit this association by employing the unique radiopharmaceutical, 131I-MIBG, which is recognized and taken up by the APUD system to monitor disease activity in patients with small cell carcinoma of the lung. A total of eight patients with biopsy proven, metastatic small cell carcinoma of the lung were studied. 131I-MIBG was synthesized in our laboratory by reacting metaiodobenzylamine hydrochloride with cyanamide with subsequent solid phase radioiodination. A dose of 0.5 mCi radiopharmaceutical was injected and images obtained on a large field of view gamma camera with a high energy parallel hole collimator at 2, 24, and either 48 or 72 h. Images were compared with known focal areas of metastatic disease demonstrable on computed tomographic scan, chest roentgenogram or bone scan. We were unable to detect reproducible correlations between the images produced by conventional radiographic techniques and the images produced by our radiopharmaceutical. We conclude that this agent will probably not be useful for localization of metastatic small cell lung carcinoma.
3-Iodobenzylguanidine↗
Evaluation of six new 99mTc-IDA agents for hepatobiliary imaging.
IDA derivatives of three substituted benzothiazol, and two substituted chlorophenyl and one substituted pyrazoline compounds have been labeled with 99mTc and screened with four rat models with hepatocellular dysfunction manifesting varying degrees of change of liver architecture and hepatocellular damage associated with an active parenchymal destruction, fatty metamorphosis and cirrhosis. Organ distribution studies at 1 h postinjection have been compared in normal and diseased animal models for each agent labeled with 99mTc and with 99mTc-Disofenin (Disida) and Lidofenin (Hida) and 131I-Rose Bengal. From the data obtained with the six new IDA derivatives, the distribution kinetics of 99mTc-Arclophenin, (N-N'-2-benzoyl-4-chlorophenyl)carbamoylmethyl) imino diacetic acid (Phenida), are closely comparable to 99mTc-Disofenin in all animal models. Crossover patient studies (n = 14) for clinical evaluation of 99mTc-Arclophenin vs 99mTc-Disofenin indicate the close similarity of the 2 agents with regard to blood pool retention, gross liver/heart ratios and liver washout, suggesting Arclofenin as a suitable agent for hepatobiliary function studies. The impaired hepatocellular animal models presented should serve for fast screening of hepatobiliary agents and enable comparison of a series of closely related compounds.
Adult↗
Uptake of technetium 99m hepatobiliary imaging agents by cultured rat hepatocytes.
Quantitation of initial uptake of the cholescintigraphy agents, 99mTc-Lidofenin, 99mTc-Disofenin, 99mTc-Mebrofenin, and 99mTc-Arclofenin, in short-term cultured rat hepatocytes revealed a marked reduction at 4 degrees C as compared with 37 degrees C. Depletion of adenosine triphosphate by preincubation of cells in sodium azide and 2-deoxyglucose reduced initial uptake of 99mTc-Disofenin at 37 degrees C by 50% (p less than 0.05), suggesting an energy-dependent mechanism. At 37 degrees C, 99mTc-Mebrofenin and 99mTc-Disofenin had the greatest rate of uptake. 99mTc-Disofenin and 99mTc-Lidofenin uptake was inhibited by 20 microM sulfobromophthalein, bilirubin, taurocholate, deoxycholate, chenodeoxycholate, and cholate, suggesting a common anionic transport mechanism. Uptake of 99mTc-Disofenin was unaffected by removal of NaCl from medium, suggesting that its transport did not proceed by the primary high-affinity uptake pathways associated with sulfobromophthalein and taurocholate, which require Cl- and Na+, respectively. 99mTc-Mebrofenin uptake was inhibited only modestly by taurocholate, deoxycholate, and bilirubin (p less than 0.05) and 99mTc-Arclofenin uptake was not inhibited by the organic anions studied. These results suggest that 99mTc-Mebrofenin and 99mTc-Arclofenin might be advantageous for cholescintigraphy in severely jaundiced patients. The relatively simple in vitro methodology described in this study may be useful in the design and screening of potential new agents before proceeding to animal studies or clinical trials.
Aniline Compounds↗
Red blood cell labeling with technetium-99m. Effect of radiopaque contrast agents.
Radiographic contrast agents have been reported in the literature to interfere significantly with red blood cell (RBC) labeling in vivo by Tc-99m. Moreover, in the presence of contrast agents, red cells have been known to undergo significant morphologic changes. These observations led to the current RBC labeling study in patients (N = 25) undergoing procedures with the administration of contrast media. Before and after contrast administration, blood samples were drawn from each patient into vacutainer tubes containing heparin and RBC labeling was performed using 1-ml aliquots of these samples following the Brookhaven National Laboratory protocol. The differences in average percentage labeling yield with and without contrast media were not significant. In vivo labeling in hypertensive rats with administration of contrast media up to 600 mg likewise consistently gave high labeling yields at all concentrations. Purported alterations in cell labeling attributed to contrast agents are not reflected in these studies, and other pathophysiologic factors need to be identified to substantiate the previous reports. In vitro study offers a potentially useful and simple method to delineate effects of various agents on cell labeling.
Adult↗
N-hydroxysuccinimide-hippuran ester: application for radiolabeling of macro-molecules.
A method for synthesis of N-hydroxysuccinimide ester of radioactive hippuran is developed in order to label human serum albumin in a simple and efficient manner. Organ distribution in mice and rats for the labeled albumin preparation and the commercial radioiodinated serum albumin is similar. Hippuran metabolite released from the labeled preparation into the blood stream results in its rapid urinary clearance. The hippuran labeling method offers a mild and rapid protocol for radioiodine labeling of proteins and antibodies for application in diagnostic nuclear medicine procedures.
Animals↗
Evaluation of the renal clearance of technetium-99m PAHIDA in dogs.
The renal clearance of the technetium-99m complex of para[(biscarboxylmethyl)-aminomethylcarboxyamino]hippuric acid ([99mTc]PAHIDA), has been previously studied in rodents and falls between that of [99mTc]DTPA (diethylenetriaminepentaacetic acid) and iodine-131 (131I) orthoiodohippuran (OIH). To investigate the effect of species variation, the plasma clearance of [99mTc]PAHIDA was investigated in dogs. The plasma disappearance of the renal agent approached that of [99mTc]DTPA and was significantly less than that of OIH. Despite the structural similarities of the PAHIDA ligand and aminohippurate, the [99mTc]PAHIDA complex undergoes little, if any, tubular secretion in the canine kidney.
Aminohippuric Acids↗
Chromium 51-ethylenediaminetetraacetate test: a useful test in the assessment of inflammatory bowel disease.
We evaluated the usefulness of urinary excretion values in assessing mucosal damage in inflammatory bowel disease after administration of chromium 51-labeled EDTA either orally or rectally. In the oral study, 19 controls, 18 patients with Crohn's disease, and 13 patients with ulcerative colitis were given 100 microCi 51Cr-EDTA by mouth. The amount of 51Cr-EDTA in a 24-hour urine collection was expressed as a percentage of the ingested dose. The patients with Crohn's disease of the small bowel excreted 6.3% +/- 4.3%, which was significantly (P less than 0.001) higher than the percentage in patients with ulcerative colitis (1.7% +/- 1.1%) and controls (1.4% +/- 0.6%). In the enema study, 19 patients with ulcerative colitis, two with Crohn's disease, two with radiation colitis, and four controls (spastic colitis, lactose intolerance) were given 100 microCi 51Cr-EDTA by retention enema. The patients with active colonic inflammation excreted 8.4% +/- 3.9% of the dose given by enema, which was significantly (P less than 0.01) higher than in other controls (1.9% +/- 0.91%) or patients with inactive colitis (2.2% +/- 1.9%). The 51Cr-EDTA excretion test is a safe, inexpensive test useful in evaluating patients with inflammatory bowel disease. It can be given orally to screen patients with abdominal complaints who are suspected of having Crohn's disease involving the small intestine, and when given by enema it provides additional objective assessment of idiopathic ulcerative colitis or proctitis.
Administration, Oral↗
Altered distribution of technetium-99m sodium pertechnetate associated with antimicrobial therapy.
Three patients underwent brain scanning for evaluation of central nervous system disease and were simultaneously treated for infectious diseases unrelated to the central nervous process. All revealed intense vascular pooling on their brain images. The imaging studies had been performed following the administration of Tc-99m pertechnetate. None of the patients had prior nuclear medicine examinations to suggest the causal effect of stannous ion as a source of interference. All of the patients were on combination antimicrobial drugs: two on sulfamethoxazole and trimethoprim, and one on isoniazid and ethambutol. One patient revealed 75% Tc-99m red cell tagging. Another patient's repeat brain scan with Tc-99m DTPA revealed normal distribution. Our findings suggest that patients on antimicrobial combination drug regimens who require brain scans should be imaged routinely with agents other than Tc-99m.
Aged↗
Data acquisition using a scintillation detector interfaced to a personal microcomputer.
A method is described for interfacing a cadmium telluride semiconductor nonimaging detector to a personal microcomputer in order to store and display nuclear medicine data. There was virtual identity between the count rates stored in the computer and those recorded from the detector's display, demonstrating that the computer accurately acquired data from the probe without erroneous loss or addition of data. Interfacing a nonimaging detector to a microcomputer may provide an extremely versatile method of acquiring, storing, and displaying nuclear medicine data.
Computers↗
Radionuclide-labeled red blood cells: current status and future prospects.
Radiolabeling of red cells and their clinical and research application in nuclear medicine constitute an area of continued interest and steady growth during the past two decades. Significant advances have been made so that at the present time, radiolabels with sufficient in vitro and in vivo stability are available for diverse applications. Technetium-99m-labeled red cells in particular have revolutionized the field of cardiovascular nuclear medicine by making possible the external evaluation of various heart parameters with minimum radiation dose or trauma to the patient. Among other areas of study that use 99mTc -RBC are blood pool imaging, detection of vascular malformations, red cell mass determination, detection of gastrointestinal bleeding, and of hemangiomas. Heat-damaged 99mTc -RBC find application in spleen imaging, accessory spleen localization, detection of GI bleeding, and in other areas. A critical evaluation is presented of the various in vitro and in vivo labeling techniques that are currently available for red cell labeling. Even though the presently used procedures provide satisfactory labeled preparations, ideal radioisotopic RBC labels remain to be developed. Intermediate (2-3 days) as well as long-lived (approximately 30 days) radionuclidic labels are highly desirable for a number of clinical procedures where 99mTc is not useful due to its short half-life. A clearer understanding of the mechanistic aspects of various labeling reactions is expected to aid in the design of better and improved RBC labels that will help fulfill various areas of need in nuclear medicine applications. New approaches such as the use of radiolabeled antibodies to red cell antigens, or labeling specific receptor sites in the cell may lead to substantial improvements in the labeling methodology and could yield labeled cells with the least damage and maximum in vivo stability.
Chromium Radioisotopes↗
Quantitative evaluation of cerebrospinal fluid shunt flow.
We describe a rigorous method for measuring the flow of cerebrospinal fluid (CSF) in shunt circuits implanted for the relief of obstructive hydrocephalus. Clearance of radioactivity for several calibrated flow rates was determined with a Harvard infusion pump by injecting the Rickham reservoir of a Rickham -Holter valve system with 100 microCi of Tc-99m as pertechnetate. The elliptical and the cylindrical Holter valves used as adjunct valves with the Rickham reservoir yielded two different regression lines when the clearances were plotted against flow rates. The experimental regression lines were used to determine the in vivo flow rates from clearances calculated after injecting the Rickham reservoirs of the patients. The unique clearance characteristics of the individual shunt systems available requires that calibration curves be derived for an entire system identical to one implanted in the patient being evaluated, rather than just the injected chamber. Excellent correlation between flow rates and the clinical findings supports the reliability of this method of quantification of CSF shunt flow, and the results are fully accepted by our neurosurgeons.
Adult↗
Stannous ion quantitation in 99mTc-radiopharmaceutical kits.
A simple and inexpensive method for the estimation of stannous ion, Sn (II), in radiopharmaceutical kits is described. The method used is a potentiometric titration of Sn (II) in 1 N HCI medium, using potassium iodate as the oxidizing agent in an atmosphere of nitrogen. The apparatus includes pH meter, a platinum electrode, and a simple titration cell. Several commonly used radiopharmaceutical kits were analyzed for their Sn (II) content using this method. These studies indicate that the procedure can be used, as a routine quantitative test for the Sn (II) content of various 99mTc-labeled radiopharmaceuticals.
Hydrogen-Ion Concentration↗
Radiopharmaceuticals for hepatobiliary imaging.
Tests for liver function have by and large centered around clinical laboratory diagnostic procedures for a number of years. Besides these, radiographic imaging procedures, including oral cholecystography and intravenous cholangiography, serve a very useful purpose, but several of them are invasive and involve a certain degree of risk from the administered contrast media as well as discomfort to the patient. The cholescintigraphic procedures, though noninvasive, have not played a significant role in the evaluation of hepatobiliary disorders prior to the introduction of the currently available. 99mTc-labeled IDAs. These new hepatobiliary agents offer many advantages over the previously utilized radiopharmaceuticals (131I-rose bengal in particular) in terms of the high degree of specificity for localization in the gallbladder with rapid extraction rates by the polygonal cells of the liver and very low excretion via the GU tract. A detailed understanding of the structure distribution relationship of the various groups in the complex enable the design of agents with an improvement in hepatobiliary specificity and other desirable characteristics. In many clinical situations, even in patients with high bilirubin levels, the 99m-Fc-labeled IDAs offer far superior clinical information over the alternative diagnostic imaging modalities. Further, the absorbed radiation dose imparted to the critical organs is far lower than with the older agents. Thus, the introduction of the cholescintigraphic procedures with the 99mTc-labeled IDAs have ushered in a new phase in the diagnostic workup of patients with impaired hepatocellular function and other biliary disorders.
Biliary Tract↗
Renal radiopharmaceuticals--an update.
Noninvasive radionuclide procedures in the evaluation of renal disease have been accepted increasingly as effective and valuable alternatives to older clinical methods. The development of suitable radiopharmaceuticals labeled with high photon intensity radionuclides and with 99mTc in particular has stimulated this modality during the last few years. Currently several nearly ideal agents are available for anatomical and functional studies of kidney imparting very low absorbed radiation doses. These include 99mTc-GHA and 99mTc-DMSA for renal morphology and differential function evaluation, 99mTc-DTPA for GFR and 123I orthoiodohippurate for ERPF measurements. A suitable agent as a replacement for the latter labeled with 99mTc is actively being sought. Computer-assisted processing of dynamic renal function studies enables the observer to obtain a wealth of information related to the renal extraction, uptake, parenchymal transit and pelvic transit parameters of the agent administered into the bloodstream. Each of these parameters either globally or differentially contributes to a detailed evaluation of renal disease states. Several of these procedures have been validated against classical techniques clinically but more detailed information is being sought with the recently introduced radiopharmaceuticals. With the detailed validation and increasing recognition of the clinical utility of several of the radionuclidic procedures at many centers, it is hoped that radionuclide assessment of renal disorders ultimately will be made available routinely at all medical facilities.
Carbon Radioisotopes↗
Radiopharmaceuticals in cardiovascular nuclear medicine.
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Coronary Circulation↗
Static testicular imaging utilizing 201Tl.
Successful testicular imaging of rat and rabbit testes was achieved utilizing the radiopharmaceutical Thallium-201. These observations indicate the usefulness of Thallium-201 as an agent for testicular imaging and suggest a clinical application in localizing the impalpable testis in humans.
Animals↗