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Alteration of the organ uptake of the (99m)Tc-radiopharmaceuticals, (99m)Tc-DPD, (99m)Tc-DMSA, (99m)Tc-tin colloid and (99m)Tc-MAA, induced by the applied cytotoxic drugs methotrexate sodium and cyclophosphamide.

AIM: To investigate the influence of certain cytotoxic drugs on the organ uptake of the following (99m)Tc-radiopharmaceuticals: (99m)Tc-2,3-dicarboxypropane-1,1-diphosphonic acid ((99m)Tc-DPD), (99m)Tc-meso-2,3-dimercaptosuccinic acid ((99m)Tc-DMSA), (99m)Tc-tin colloid and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). Methotrexate sodium and cyclophosphamide were used as models to evaluate these effects. METHODS: Two groups of healthy male Wistar rats were treated separately by oral application of the drugs for 7 days. On the eighth day, each of the (99m)Tc-radiopharmaceuticals was applied in a separate group of treated animals. They were sacrificed at different time intervals and the radioactivity in the organs of interest was measured. The organ uptake of the (99m)Tc-radiopharmaceuticals in an additional control group of animals was also studied. RESULTS: The results obtained showed an alteration in the organ uptake of (99m)Tc-radiopharmaceuticals in animals treated with cytotoxic drugs. In rats treated with methotrexate sodium, there was a higher uptake of (99m)Tc-DMSA in the bones, stomach and intestine, a higher uptake of (99m)Tc-DPD in the bones, intestine, blood and muscle, a lower uptake of (99m)Tc-tin colloid in the liver and a lower accumulation of (99m)Tc-MAA in the lungs. Cyclophosphamide-treated animals showed enhanced uptake of (99m)Tc-DMSA in the kidneys, a twofold enhanced uptake of (99m)Tc-DPD in all organs except the stomach, a decreased uptake of (99m)Tc-tin colloid in the lungs, spleen and kidneys and a significantly decreased uptake of (99m)Tc-MAA in the lungs. CONCLUSION: These results confirm that both methotrexate sodium and cyclophosphamide may alter the organ uptake of (99m)Tc-radiopharmaceuticals in experimental animals.

Animals↗

[The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid].

Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve.

Adult↗

The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis.

To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.

Bone Marrow↗

A review of cardiac imaging with sestamibi and teboroxime.

Overall, it is clear that the two new technetium-labeled compounds can provide diagnostic myocardial perfusion imaging both at stress (exercise and pharmacologic) and rest, but they have very different mechanisms of transport in comparison to each other and to thallium. Therefore, new imaging protocols will need to be developed and refined by practical experience as the use of these agents expands. Further investigative work needs to be done to optimize protocols and computer processing of images. In addition, special clinical situations will become associated with the use of these new compounds. Nuclear cardiology will continue to advance during this time of great changes and challenges if informational exchange on these topics continues to flourish and critical clinical trials are completed.

Coronary Disease↗

Radionuclide measurement of liquid and solid gastric emptying in normal subjects in Singapore.

Scintigraphic methods for liquid and solid gastric emptying were utilised to study normal patterns in 21 volunteers. Of these, 19 had solid emptying studies and 14 had liquid emptying studies. The liquid study lasted 1/2 hour, while the solid study was for 1 hour. The gastric emptying half-time (T 1/2), as well as percentage retention at 15 minutes (liquids), and at 60 minutes (for solids) were noted. The time-activity curves were also corrected for tissue attenuation. Results indicated normal average liquid emptying T 1/2 to be 14.2 minutes, while that for solids was 116 minutes.

Adult↗

Importance of cholescintigraphy and inferior vena cava flow studies in the differential diagnosis of hepatocellular carcinoma.

In order to assess the usefulness of inferior vena cava flow studies and cholescintigraphy complementary to the routine static liver scintigraphy in the differential diagnosis of hepatocellular carcinoma (HCC), we studied 37 patients with a proven diagnosis of HCC and 11 patients with a liver abcess or cyst. The procedure followed was 1) a 99mTc-colloid flow study of the inferior vena cava (IVC) and iliac veins followed by static liver imaging and 2) cholescintigraphy using a dynamic acquisition mode to determine the perfusion as well as the concentration/excretion of the liver and pathological area. The hepatic perfusion index (HPI) was calculated by the "slope" method of Sarper et al.: Radiology 141:179-184 (1981) and the "area" method of Biersack et al.: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklear medizin. Erganzungsband 126:47-52 (1977). The results were compared with data previously collected in patients without liver disease (control) and other liver pathologies.

Carcinoma, Hepatocellular↗

Experimental study of iron effect on the liver function.

The effect of iron on the liver function was studied in rats. A total of 40 rats were divided into four groups. Group 1 was given iron; Group 2, carbon tetrachloride; Group 3, a combination of iron and carbon tetrachloride; and Group 4 was the control. The changes in liver function were evaluated by using hepatobiliary and liver scintigraphy as the index of hepatocyte function and reticuloendothelial system function, respectively. Determination of liver CT number and a histological study were made at the same time. The administration of iron activated the reticuloendothelial system function per unit of liver weight. However, because of the decrease in liver weight, the total reticuloendothelial system function did not change at all. In the group given iron and carbon tetrachloride, liver cirrhosis and siderosis in the reticuloendothelial system occurred. Dysfunction in the reticuloendothelial system was more severe in this group than in the group given carbon tetrachloride only, by hepatocyte dysfunction was more mild. It is doubtful that the administration of iron after liver dysfunction had developed, which caused acceleration of fibrosis and reduction of liver blood flow, led to the enhancement of the reticuloendothelial system dysfunction.

Animals↗

Absolute quantification of pharmacokinetic distribution of RES colloids in individuals with normal liver function.

Estimates of the radiation dose resulting from liver-spleen scintigraphy 99Tcm-labelled colloids are based on pharmacokinetic data mainly determined in animals. The aim of this study was to check the pharmacokinetic data by direct, absolute in vivo quantification in man. For this purpose appropriate methods of measurement were developed, or procedures taken over from literature were modified. Liver and spleen activities were directly measured using a double-energy window technique. Activities in other organs were quantified by conjugate whole-body scans. All measurement procedures were checked using the whole-body Alderson phantom. Pharmacokinetic data for sulphur colloid, tin colloid, human serum albumin (HSA) millimicrospheres, and phytate were obtained in 13 to 20 normal subjects for each type of colloid. Depending on the colloid type liver uptake was between 54 and 75% of the total administered dose (TAD) and spleen uptake was 3.5 to 21% TAD. Activity measured in blood, urine, lung and thyroid proved to be far from negligible. The results of this work suggest a correction of the animal-based data of colloid distribution and radiation dose on the basis of the direct measurement of absolute uptake in man.

Adult↗

Radiopharmaceuticals for spleen and bone marrow studies.

The spleen and bone marrow have important hematologic functions. Evaluation of bone marrow alone may be incomplete, unless the function of the spleen is studied also. In addition to hematologic functions, each organ has unique characteristics that may need to be evaluated in assessing its activity. The evaluation of the distribution of reticuloendothelial cells, through the phagocytosis of radioactive particles, provides the basis for most of the morphological and functional studies of these organs. During the past three decades, a variety of radioactive agents have been prepared and examined. Among them, colloids of 99mTc, heat-damaged 99mTc labeled RBCs, and the radionuclides of iron and indium, make possible the functional and morphological examination of the spleen and bone marrow by external scintigraphy.

Animals↗

Preparation and biokinetic evaluation of various halogenated iminodiacetic acid-type compounds labeled with technetium-99m for hepatobiliary scintigraphy in the baboon (Papio ursinus) model.

In an evaluation of various 99mTc-labeled halogenated (F, Cl, Br, I) iminodiacetic acid (IDA) derivatives for hepatobiliary scintigraphy, it was found that, in the baboon model, none of these compounds performed as well as did disida. F-IDA was least effective, with the lowest biliary excretion and highest renal participation, but multihalogen substitution as in penta-F-IDA increased the biliary specificity and reduced urinary excretion to the extent that penta-F-IDA scored second to disida and even above I-IDA, with its high molecular weight. Surprising also was the relatively good performance of Cl-IDA compared to Br-IDA and I-IDA.

Animals↗

99Tcm-polyclonal IgG and 99Tcm nanocolloid scans in orthopaedics: a comparison with conventional bone scan.

The bone scan is sensitive in detection of active bone/joint lesions. A normal bone scan virtually excludes the presence of an inflammatory process with high precision, but the poor specificity of bone scans is well known. In recent years, various new agents including 99Tcm-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells, nanocolloid, polyclonal IgG, anti-granulocyte antibody, 111In-labelled IgG, leucocytes, chemotactic peptides etc. have been widely evaluated in inflammatory imaging, especially in the orthopaedic context. This study was undertaken to compare the usefulness of 99Tcm-nanocolloid and 99Tcm-polyclonal IgG in the detection of focal bone/joint inflammation. Twenty-seven patients with a common presentation of bone/joint pain resulting from various pathologies were included in the study. A total of 47 lesions were imaged. The overall sensitivity and specificity of both nanocolloid scan and IgG scan were identical with 95% sensitivity and 100% specificity, in detecting inflammatory foci. However, specificity dropped to 18% with nanocolloid scans and 16% with IgG scans when an attempt was made to distinguish noninfective from infective inflammatory processes; thus neither type of scan permits differentiation between septic and nonseptic inflammatory processes with sufficient accuracy. As both nanocolloid and IgG scans are equally sensitive and specific in detecting inflammation, the choice of type of scan will depend on cost, imaging time and availability of the radiopharmaceutical.

Adolescent↗

Phosphate compounds in bone scanning.

Bone scanning with radioactive isotopes has been used to study a wide variety of disorders. Recently certain phosphate compounds, labelled with technetium, have been used as bone scanning agents. The comparative merits of three technetium-labelled phosphate compounds currently available for bone scanning--pyrophosphate, tripolyphosphate and ethylhydroxydiphosphonate (EHDP) have been compared in rabbits. Each substance was injected into ten rabbits and blood was withdrawn at regular intervals. The animals were killed at four hours and the blood and tissue samples were assayed for radioactivity. The results show that EHDP has a more rapid blood clearance than the other two agents, with a resultant improvement in the bone to soft-tissue ratio. Of the three substances investigated technetium-labelled EHDP was the best and might allow the technique of scanning to be used on a wide scale for the general study of bone and its pathology.

Animals↗