99mTc-DTPA and 99mTc-DMSA renal gamma imaging in the surveillance of patients with conduit urinary diversion

We studied renal anatomy and function using ^99mTc-2-3 dimercaptosuccinic acid (DMSA) and ^99mTc-diethylenetriaminepentaacetic acid (DTPA) in 27 patients with conduit urinary diversion. In this condition, free ureteral reflux is often associated with bacteriuria, and these factors are thought to precipitate progressive renal deterioration. Gamma-camera images provided valuable information concerning the structure of the renal parenchyma, the function of individual kidneys and possible ureteral obstruction, thus helping us to decide whether or not to instigate further treatment. The information gained using renal gamma imaging with ^99mTc-DTPA and ^99mTc-DMSA was complementary and partly overlapping. We preferred the use of ^99mTc-DTPA because of its ability to visualise the ureters and the region of ureteroconduit anastomosis. Using diuretic medication, we were able to differentiate true ureteral obstruction from atony in 9 patients using ^99mTc-DTPA.     

Assessment of split renal function with 99mTc-aprotinin

The aim of this work is to correlate the net kidney uptake of 99mTc-aprotinin (TcA) in 103 subjects with separate effective renal plasma flow (ERPF) and some blood chemistry parameters at 90, 180, and 360 min postinjection both in the normal and diseased kidney. Correlations found with separate ERPFs are highly significant at any time (P less than 0.001). However, although the slope of the regression line is steeper at 180 min, r tends to deteriorate slightly with time postinjection and a higher intercept on the y axis; this pattern is more pronounced if diseased kidneys are considered separately. The following are probably related to the renal handling of TcA: Early scans better reflect blood flow to the kidney, while later scans are more related to the metabolism/excretion tubular mechanisms; correlations found with urea, creatinine, urea clearance, and creatinine clearance are highly significant at any time; in 20 additional patients with diseased kidneys, renal uptake measurements done 360 min postinjection first with TcA and then with DMSA showed better correlations with ERPF employing TcA. Our results indicate that TcA is a feasible indicator of split renal function even at 90 min postinjection when a scan is easily carried out on an outpatient basis.     

Extrarenal scientigraphic aspects of kidney transplant scans obtained with99mTc-DTPA

In a retrospective study, 300 scans obtained with^99mTc-DTPA of 100 kidney transplant recipients were studied. The aim was to look for extrarenal scintigraphic aspects encountered specifically in renal transplant scintigraphy and to determine whether some of these phenomena could interfere with adequate interpretation. The most important phenomena seen were radioactivity in the uterus and a cold spot in the pelvis minor caused by a urine filled bladder. If the phenomena that can be encountered are known, the risk of incorrect evaluation is small. In addition, we report on the occurrence of statsis due to disturbed urine flow.     

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.     

In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals

Purpose In vivo quantification of radiopharmaceuticals has great potential as a tool in developing new drugs. We investigated the accuracy of in vivo quantification with multi-pinhole single-photon emission computed tomography (SPECT) in rats.Methods Fifteen male Lewis rats with different stages of renal dysfunction were injected with 50 MBq ^99mTc-dimercaptosuccinic acid. Four to six hours after injection, SPECT of the kidneys was acquired with a new four-headed multi-pinhole collimator camera. Immediately after imaging the rats were sacrificed and the kidneys were counted in a gamma-counter to determine the absorbed activity. SPECT data were reconstructed iteratively and regions of interest (ROIs) were drawn manually. The absolute activity in the ROIs was determined.Results Uptake values ranging from 0.71% to 21.87% of the injected activity were measured. A very strong linear correlation was found between the determined activity in vivo and ex vivo (r ²=0.946; slope m=1.059).Conclusion Quantification in vivo using this multi-pinhole SPECT system is highly accurate.     

Breast-milk radioactivity after 99mTc-MAA lung studies

The concentration of radioactivity in the breast milk of four nursing mothers who had received injections of ^99mTc macroaggregated albumin (MAA) was measured. The results were compared with previous measurements, and an estimate of the radiation dose to an infant from internal and external sources was obtained for various times of recommencement of breast feeding. It is suggested that feeding can recommence earlier than the normally recommended 24 h if this is thought to be clinically desirable.     

Clinical approach to renal study incidental to99mTc-MDP bone scintigraphy

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.     

Technetium-99m mercaptoalbumin as a potential substitute for technetium-99m labelled red blood cells

Technetium-99m labelled red blood cells (^99mTc-RBCs) are far superior to ^99mTc-labelled human serum albumin (^99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical ^99mTc-mercaptoalbumin with long retention in the vascular system, that could replace ^99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with ^99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure ^99mTc-mercaptoalbumin. Stable ^99mTc-mercaptoalbumin complexes could be formed in 90%–95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25: 1 ratio and deprotection with NH₂OH. The stability of the resulting ^99mTc-mercaptoacetyl-albumin (^99mTc-MAHSA) and ^99mTc-dimercaptopropionyl-albumin (^99mTcDMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional ^99mTc-HSA preparations. ^99mTc-DMP-HSA approaches the behaviour of ¹²⁵I-HSA quite well in both animal species. A preliminary study with ^99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of ^99mTc-RBCs and clearly higher than that of a common ^99mTc-HSA preparation. The results indicate that these ^99mTc-mercaptoalbumins and especially ^99mTc-DMP-HSA are very promising as a practical alternative to ^99mTc-RBCs.K.A. Verbeke is a Research Assistant for the Belgian National Fund for Scientific Research     

Better visualization of a lung tumour with 99mTc-DPD than with 99mTc-glucoheptonate or 67Ga-citrate

A case of a squamous cell lung carcinoma detected with ^99mTc-DPD, ⁶⁷Ga-citrate and ^99mTc-glucoheptonate (GH) is reported. The highest uptake was seen with DPD and the lowest with ⁶⁷Ga. Emission-computed tomography was very useful in DPD imaging but gave less new information in GH and ⁶⁷Ga studies in comparison to traditional planar imaging. The patient had been given both irradiation and chemotherapy, which might be the cause of good accumulation of DPD and rather poor accumulation of GH and ⁶⁷Ga.     

The stability of 99mTc-DTPA and 99mTc-HIDA following ultrasonic nebulisation

The stability of ^99mTc-DTPA (diethylenetriamine-pentaacetic acid) and ^99mTc-HIDA (2,6-diethylacetanilidoiminodiacetic acid) were evaluated following ultrasonic nebulisation. The results confirm that either of these radiopharmaceuticals can be used in our nebuliser without significant radiochemical breakdown.     

Uptake of 99mTc-phytate in osteosarcoma cases

During routine liver spleen scintigraphic studies using ^99mTc-phytate in patients with proven osteosarcoma, an unusual uptake of this radiopharamaeutical at the primary site was observed. In all, five cases have been investigated and we have observed the uptake of ^99mTc-phytate at the primary tumor site. Early and delayed imaging showed persistant concentration of the radiopharmaceutical. Studies with ^99mTc-sulfur colloid in one of the patients did not show any uptake at the tumor site.     

99mTc-MAG3: Review of pharmacokinetics, clinical application to renal diseases and quantification of renal function

About 14 years have passed since Fritzberg et al. developed 99mTc-MAG3 in 1986. The biological properties of this radiopharmaceutical are somewhat different from radioiodine labeled hippurate: it exhibits higher protein binding, slower blood clearance, higher extraction efficiency by tubular cells and larger excretion into the bile than the latter. Nonetheless, it has been widely used as the agent of choice for renal scintigraphy, diuresis renography, captopril augmented renography, and renal transplant. Renal scintigraphy with 99mTc-MAG3 can provide excellent image quality even in the presence of severely decreased renal function. 99mTc-MAG3 is also used as an alternative to radio-hippurate for quantitative measurement of effective renal plasma flow. In this review, I focused on its pharmacokinetics, simplified quantitative methods and clinical application in renal diseases.     

Scintigraphic demonstration of subcutaneous abscesses with 99mTc-labeled leukocytes

Our initial experience with the clinical application of autologous leukocytes labeled in vitro with technetium 99m is reported. An injection of 3.6×10⁸ leukocytes (83% of which were polymorphonuclear) labeled with 6.4 mCi ^99mTc was administered to a patient with subcutaneous abscesses in order to evaluate the in vivo stability of the labeling and cellular function. Scintigraphic examinations demonstrated marked accumulations of radioactivity at the sites of inflammation, suggesting that ^99mTc was efficiently bound to the cells and that the migration of polymorphonuclear leukocytes was not disturbed by the labeling procedure.     

Technetium thiodiglycollic acid (99mTc-TDG). A new radiopharmaceutical with the potential for the assessment of renal function

A mixture of hydrophilic complexes is formed on the reduction (employing tin metal as a reductant) of sodium pertechnetate ^99mTc in the presence of the ligand thiodiglycollic acid (TDG). When administered to rats, the mixture demonstrated a renal clearance rate marginally greater than Glomerular filtration rate (GFR). HPLC analysis indicated the formation of two technetium complexes of TDG. After isolation of the complexes and their administration to rats, one (complex 1) showed renal clearance similar to that of ^99mTc Diethylenetriamine pentaacetic acid (DTPA), while the other (complex 2) demonstrated renal clearance similar to that of ¹²⁵I o-iodo hippuric acid. On heating the mixture of complexes, the proportion of the faster-clearing ^90mTc TDG complex increased to 92% of the total activity, and the biodistribution of the material following heat rearrangement was equivalent to that of isolated complex 2.     

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.     

Transplant renography: 99m-Tc-DTPA versus 99m-Tc-MAG3. a preliminary note

^99mTc-MAG3 has been proposed as a replacement for both ¹³¹I-hippuran and ^99mTc-DTPA on clinical grounds. We undertook a prospective preliminary study to ascertain whether ^99mTc-MAG3 works better than ^99mTc-DTPA in the follow up of renal transplant recipients. Seventeen patients (21 renograms each MAG3 and DTPA) were studied, together, with a reference group of 10 patients in whom MAG3 and Hippuran clearance rates were determined simultaneously. As expected, ^99mTc-MAG3 analog images were excellent and ^99mTcMAG3 clearance correlated very well with ¹³¹I-hippuran clearance (r=0.978). MAG3 values were 60% of hippuran values. However, when the corresponding renographic and perfusion findings were faced with different diagnostic challenges, such as post transplant renal failure and rejection, ^99mTc MAG3 did not differ from ^99mTc-DTPA in a significant way. ^99mTc-DTPA was superior to ^99mtc-MAG3 in one case of rejection.     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

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.     

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.     

Reduction of <Superscript>99m</Superscript>Tc-sestamibi and <Superscript>99m</Superscript>Tc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of ^99mTc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, ^99mTc-tetrofosmin (TF), was also examined. Cellular uptake of ^99mTc-MIBI and ^99mTc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N₂ and 5% CO₂ reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.