[Clinical and experimental evaluation of osteotropic radiopharmaceutical preparations].
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Uptake of Tc-99m di-isopropyliminodiacetic acid (DISIDA) by hepatocellular carcinoma was assessed in 30 patients showing obvious liver defects on a Tc-99m tin colloid image. In none of these patients was there complete "filling in" of the defects, and even partial "filling in" occurred in only 11 (36.7%). There was no uptake of Tc-99m DISIDA by the primary tumor in the remaining 19 patients (63.3%). In 19 of the 30 patients an attempt was made to correlate the degree of histologic differentiation of the tumor with the uptake of DISIDA by the tumor. No difference in uptake could be demonstrated between well, moderately, and poorly differentiated tumors. Tc-99m DISIDA was not taken up by pulmonary metastases in the only two patients tested. We conclude that imaging with Tc-99m DISIDA in conjunction with Tc-99m colloid is of no value in the specific diagnosis of hepatocellular carcinoma.
For the recognition and characterisation of oesophageal motor disorders, manometry represents the most reliable tool but yields no information on bolus transport. The transport can be quantitated by radionuclide techniques. The patient is positioned supine beneath a gamma-camera and instructed to swallow a radiolabelled bolus in a single gulp. Using a marker over the cricoid and the activity in the stomach as landmarks, regions of interest are drawn representing the upper, middle and lower third of the oesophagus and the gastric fundus. Activity-time curves enable one to recognise the clearance patterns in these regions. In combination, manometric and radionuclide transit studies recognise a higher number of motor disorders than either procedure alone. Radionuclide methods also are the most reliable and sensitive to quantitate gastric emptying. Procedure, meal size and composition as well as patient position must be standardised and correction techniques applied. The emptying of solid and liquid meal constituents can be evaluated concomitantly. Solids start to empty only after a lag phase of varying extent. With semi-solid meals, which are emptied at the same rate as solid meals of identical composition in the postlag phase, the recording time can be considerably shorter. Besides gastric emptying, the amplitude, frequency and propagation velocity of antral contractions can be recorded using serial images of short frame time and specially devised analytic techniques.
The quality of a number of commercial human albumin kits used at Danish hospitals for preparation of 99mTc-labelled human serum albumin has been investigated by column chromatography and HPLC. In general, the radiochemical purity was found to be low (75% or less). In some cases with a poor radiochemical purity, the main radiochemical impurity, 99mTc-labelled tin colloid, amounted to 29% or more. A large molar tin to albumin ratio seems to lead to a low radiochemical purity and it is suggested that products with a high content of stannous chloride may be more correctly termed 99mTc-albumin/tin-colloid kits.
Sentinel node biopsy (SNB) in breast cancer is a promising surgical technique that avoids unnecessary axillary lymph node dissection. To optimize lymphatic mapping with radiopharmaceuticals, mammary lymphoscintigraphy with 30-50 MBq of technetium-99m-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSAD), technetium-99m-human serum albumin (99mTc-HSA), or technetium-99m-tin colloid (99mTc-TC) were investigated in 69 cases of primary breast cancer. Dynamic early images were obtained during the first 30 or 40 minutes, and static delayed images were obtained 6 hours after tracer injection. Hot spots as sentinel lymph nodes (SLNs) appeared in 51 of 69 cases (74%): in early images in 27 cases and in delayed images in 24 cases. SLNs were visualized more frequently in 23 of the 26 cases (88%) treated with 99mTc-HSAD and in 21 of the 24 cases (88%) treated with 99mTc-HSA than in only 7 of the 19 cases (37%) treated with 99mTc-TC. In 26 of the 51 cases, SLNs were identified as faint spots in delayed images. There was a significant difference in the first appearance of SLNs on the lymphoscintiscan between 43 cases of dense breast parenchyma and 26 cases of fatty breast parenchyma. These results suggest that 99mTc-HSAD or 99mTc-HSA is acceptable for lymphatic mapping, but in cases which have faint spots in delayed images or fatty breast parenchyma, gamma probe-guided SNB may result in failure or misleading false-negative SLNs.
The labeling of human serum albumin (HSA) with 99mTc using Sn(II) as the reductant has been reinvestigated in view of the possibility of formation of Sn-Tc colloids. Preparations of 99mTc-HSA and mixtures of 99mTc-TcO-4 with Sn(II)Cl2 have been analyzed by means of gel chromatography using various gel matrices and eluents. No Sn-Tc colloids could be eluded from samples of 99mTc-HSA preparations. The percentage of labeling was about 90%. A comparative investigation of a number of gel-chromatographic systems for the detailed analysis of 99mTc-HSA has been made. It is found that a long column with Sephadex G-200 gives the best results.
The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.
Functional asplenia is described in the case report of an 80-year-old woman who was admitted with Sézary syndrome. The spleen could not be visualized by a Tc-99m tin colloid (SnC) liver and spleen scan, but was visualized by a Tc-99m sulfur colloid (SC) scan, suggesting a different mechanism in accumulation of SnC and SC in the spleen. In-111 oxine labeled Sézary cells could be found in the spleen, bone marrow, and lymph nodes.
A patient with recently diagnosed severe acute hepatitis underwent serial liver scintigraphy with Tc-99m Sn colloid and Tc-99m DTPA-galactosyl human serum albumin. In initial studies, radionuclide distribution on Tc-99m DTPA-galactosyl human serum albumin scintigraphy was completely discrepant to that on Tc-99m Sn colloid scintigraphy. In a follow-up study 1 month later, the distribution of both radionuclides in the liver appeared relatively homogeneous. The uptake of Tc-99m DTPA-galactosyl human serum albumin and Tc-99m Sn colloid reflects the function of hepatocytes and Kupffer cells, respectively. Both kinds of scintigraphic study may be helpful to assess histopathologic change of different hepatic tissue architectures.
In patients receiving locoregional therapy for liver metastases degradable microspheres are being increasingly used in an attempt to improve cytotoxic delivery to the tumour. However, counterproductive arteriovenous shunting through the liver following intrahepatic arterial injection can occur, leading to deposition in the lung. Measurement of the degree of shunting is important in the monitoring of this kind of therapy. In this study we describe the use of technetium-labelled microspheres of serum albumin (99Tcm MSA) to measure baseline shunting during hepatic arterial perfusion scintigraphy in five patients with liver metastases of colorectal origin, and assess the significance of the values obtained for relative lung uptake (RLU) which we define as: RLU = Activity in lung field/Activity in liver + lung fields X 100%. We found that shunting was less than 5% in all cases, zero shunting occurring in 14 of the 16 patients studied. The sources of error in this technique have been assessed, the most important being the presence of free pertechnetate in the injectate. The use of Boots 10 ml vials and glass syringes respectively to dispense and administer this radiopharmaceutical reduces this error to a small predictable level. In our small group of patients, we found no evidence to suggest that use of the vasoactive agent angiotensin II significantly increases baseline shunting in patients with colorectal liver tumour.
The splenic uptake rate of Tc-sulphur colloid or Tc-tin colloid was measured and found to correlate well with splenic function. The normal tracer uptake rate was 0.0002/s-0.0006/s (measured uptake rate divided by measured injected activity). Lower values indicated hyposplenism (sensitivity = 0.97, specificity = 0.95), and values over 0.0006/s indicated hypersplenism (sensitivity = 0.96, specificity = 0.97). Higher values of splenic uptake were associated with proportional reductions in the white blood cell and platelet counts, and to a lesser extent the haemoglobin concentration in peripheral blood. Patients with rheumatoid arthritis had increased tracer uptake, but still below the criteria for hypersplenism, whereas patients with Felty's syndrome had tracer uptake rates in the 'hypersplenic' range.
Among 1 257 patients subjected to liver-spleen (RES) scintigraphy and radionuclide angiography (RNA), there were 13 cases of histologically confirmed hepatocellular carcinoma (1%). All 13 patients had scintigraphic findings indicating cirrhosis. Histologically, cirrhosis was present in only 9 out of 11 cases in which liver parenchyma was available for examination. One patient had hemochromatosis without evidence of cirrhosis. In 11 cases, the tumor was clearly demonstrated as a defect in the static scintigram. However, in 2 cases with cirrhosis and poorly differentiated hepatocellular carcinoma, the tumor nodules were hardly discernible. In RNA, the tumor displayed high activity in the arterial phase and decreasing activity during the portal phase, ending up as a defect. At RNA, the lesion was clearly outlined in 12 cases, including the 2 patients in whom the scintigraphic findings were inconclusive; in one case with severe cirrhosis and a well differentiated hepatocellular carcinoma, the tumor was barely detectable. We conclude that a combination of RNA and scintigraphy is a valuable screening which usually provides a correct diagnosis in hepatocellular carcinoma.
A non-invasive radioisotope technique for the measurement of total liver blood flow (TBF) is described. The method requires the use of two intravenously administered tracers, 99mTc (technetium 99m) human serum albumin (HSA) and 99mTc colloid. Computer analysis of first-pass time activity curves for HSA for liver and lung tissues yields values for the arterial and portal contributions to liver blood flow, from which TBF can be determined. These values are then corrected for attenuation using the images of the colloid distribution. The use of the method is illustrated in 17 subjects. Assumptions, limitations and possible applications of the technique are discussed.
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Three sets of thoraco-omphalopagous conjoined twins were investigated. The clinical findings indicated a complex shared heart in two sets, and separate cardiovascular systems in the other. These assessments were confirmed by dynamic imaging after bolus injection of Tc-99m(Sn)colloid or Tc-99m millimicrospheres. Static images were then used to establish the configurations of the shared livers. The results of these studies were in keeping with the angiographic and autopsy findings in the two sets with complex cardiac anomalies and with the surgical findings during successful separation of the third set.
We compared light pen (LPEN) and Region of Interest (ROI) computer methods in determining spleen-to-liver (S/L) ratios both in anterior and posterior images in various liver diseases. The S/L ratio was independent of age or type of colloid used (equal particle size provided). Results with corresponding LPEN and ROI programs did not differ significantly from each other. The sensitivity and specificity were tested and the anterior view yielded somewhat better results than the posterior view but the best results were obtained when both projections were used. The sensitivity for all liver diseases was 60% and the corresponding specificity 93%. In hepatocellular diseases the sensitivity was 80-100%, but the S/L ration had only 37% sensitivity for hepatic metastases. Hepatomegaly in the anterior view was found in 67% of fatty liver cases, in 25% of cirrhosis cases, in 20% of hepatitis and in 25% of metastatic livers. Splenomegaly was noted in 39-54% of patients with hepatocellular diseases but only in 4-10% of metastatic diseases.
Labelling yield and radiochemical purity, higher than 95%, of 99mTc-colloid preparations were determined by using the paper chromatography method. Less than 3% of labelled citric acid, added to the preparation as a buffer solution, has been found in 99mTc-sulphur colloid. High radiochemical purity and optimum size of colloid particles has also been proved by biodistribution studies on experimental animals. The analysis performed has shown that more than 50% of 99mTc-colloid preparations excreted by urine is 99mTcO-, the remaining past 50% being protein bound 99mTc. Biological half-time of excretion of the fast phase is the same for both preparations, i.e. 10 min, while for the slow component it is 120 min in 99mTc-S-colloid and 160 min in 99mTc-Sn colloid.
Thrombus uptake values of several 99mTc labeled radiocolloids determined using an experimental rodent model of deep venous thrombosis were correlated with particle size distributions. The thrombus uptake values increased with increasing mean particle size. The 99mTc-tin colloid had the highest thrombus uptake value of any of the colloids used in this study.