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Particle size and surface charge studies of a tin colloid radiopharmaceutical for liver scintigraphy.

The change in particle size of the liver scanning tin colloid radiopharmaceutical (Amerscan) has been determined using the non-perturbing method of photon correlation spectroscopy. Although samples of the tin colloid taken from the preparation vial immediately after preparation and allowed to remain undisturbed in the light scattering cell grow to sizes of ca. 1,200 nm radius, when samples are taken by syringe from the preparation vial at varying times, the particle size is only ca. 400 nm radius. This effect has been shown to be due to shear deflocculation within the syringe needle. Thus, as the tin colloid is always administered in the clinical situation with a syringe, the size of particle which the patient receives is satisfactory for liver uptake. The tin colloid has been shown to be essentially a charge-stabilised colloidal system from measurements of both zeta potential and effect of electrolyte on the flocculation process.

Electricity↗

In vivo estimation of renal volume using a rotating gamma camera for 99mTc-dimercaptosuccinic acid renal imaging.

The in vivo renal volume was determined using SPECT for 99mTc -DMSA renal imaging. The total renal volume was derived by summing the DMSA distribution volumes of the transaxial slices in the whole kidney. In 20 healthy subjects the renal volume in the right kidney was 220 ml for men and 195.2 ml for women, while that in the left kidney was 213 ml for men and 193.7 ml for women. Differences in those values were not statistically significant. A good correlation was found between renal volumes in both kidneys and body surface area. In 106 kidneys including solitary and pathological kidneys, individual renal volume correlated well with individual DMSA renal uptake rate which demonstrates cortical functioning mass, depending on the cortical blood flow. Thus, SPECT enables an accurate noninvasive means of estimating in vivo functioning renal volume.

Adult↗

Lymphoscintigraphy by sc injection of 67Ga-citrate.

Lymphoscintigraphy with SC injection of 67Ga-citrate was carried out on patients with lymph node metastasis and malignant lymphoma. The dose given at each injection site was about 200 muCi and scintigraphy was started about 5 min after injection. Metastatic lymph nodes and malignant lymphoma were successfully imaged. This positive delineation corresponded well to cold lesions detected by lymphoscintigraphy with 99mTc-rhenium colloid in metastatic lymph nodes. Hotter lesions in malignant lymphoma were scanned positively with 99mTc-rhenium colloid by this method. In in vitro studies, incorporation of 67Ga-citrate in HeLa S3 cells was about 4 times that in macrophages, when the incubation time was 1 h, while colloidal uptake by macrophages was 13 times that by HeLa S3 cells. The binding of 67Ga to transferrin in lymph and pinocytosis are suggested mechanisms of localization. A combination of colloid- and sc 67Ga-lymphoscintigraphy would be of value in the diagnosis of lymph node disease.

Adult↗

Dual radionuclide subtraction imaging of vertebral disc infection using an 111In-labelled leucocyte scan and a 99mTc-tin colloid scan.

Interpretation of the posterior view of an 111In-labelled leucocyte scan is difficult when infection is suspected in that region of the spine overlaid by the left lobe of the liver. A case is reported of the successful localisation of infection in this region by combining an 111In-labelled leucocyte scan with a 99mTc-tin colloid scan in a dual radionuclide subtraction technique.

Aged↗

Scintigraphy of lymphatic vessels in malignant melanoma of the skin before operation (en bloc excision).

An injection of 99mTc-labelled antimony sulphide colloid was used to show the lymphatic pathways in patients with malignant melanoma of the trunk skin. Using a gamma camera, optimal visualisation was obtained 15-30 min postinjection. Surprising deviations of the lymphatic pathways were found; therefore, this method makes it possible to plan continuity dissection appropriate to individual cases. Two examples are presented.

Antimony↗

Studies of chemical and biological properties of 99mTc-DMS (dimercaptosuccinic acid)--renal imaging agent.

Studies of the chemistry of preparation of tin chelate 2.3-dimercaptosuccinic acid (DMS) complexed with 99mTc with respect to its biological properties have been made. We have varied molar ratio of reactants (DMS:Sn/II/), concentration of Sn-DMS chelate and pH of 99mTc-DMS injection solution and examined their influence on biodistribution. Biodynamics of labeled solution at time intervals of from 0.5 to 4 h have also been measured. Animal experiments were carried out on mice and rats. Radiochemical purity was checked by paper chromatography, thin-layer chromatography, and gel-filtration through Bio-Gel P-2. A sterile, pyrogen-free lyophilized "kit" for labeling, stable for 6 months, was made on the basis of achieved results. The results of its clinical application are also reported.

Animals↗

The effect of radiopharmaceutical choice on the assessment of the relative renal function in upper urinary tract obstruction.

The relative function of the obstructed kidney (RFOK) was assessed in 43 adult patients with upper urinary tract obstruction (UUTO) using 99mTc-DTPA and 131I-ortho-iodohippurate (OIH) dynamic studies and 99mTc-DMSA dynamic and static studies. The patients were divided into five groups according to the duration and degree of obstruction. Findings were as follows: a) in patients with the first occurrence of acute severe obstruction (group 1), the relative glomerular filtration rate (GFR) was significantly less than the relative effective renal plasma flow (ERPF); b) in patients with chronic severe obstruction and long term uroinfection, the relative ERPF decreased significantly compared with the relative GFR; c) the RFOK calculated from the DMSA dynamic study was the same as both the relative GFR or ERPF in any group; d) the RFOK calculated from the DMSA static study seemed to parallel the relative ERPF more closely than the relative GFR, but in group one it was significantly higher than any of three other estimates. It is concluded that 99mTc-DTPA is the radiopharmaceutical of choice in obstructive uronephropathy, but when interpreting the RFOK, the time course and severity of obstruction, the presence or absence of uroinfection should also be considered.

Adult↗

Whole body retention of 99mTc-diphosphonate. Relation to biochemical indices of bone turnover and to total body calcium.

Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate were determined in 161 healthy adults and the results were compared to accepted biochemical markers of bone turnover. WBR was corrected for total body bone mineral (TBBM) and UE for forearm bone mineral content (BMC). Both uncorrected and corrected retention measurements were highly significantly correlated to the biochemical markers (P less than 0.001), but the r values were low (0.22-0.64). All bone turnover variables demonstrated considerably higher levels of bone turnover in postmenopausal women than in premenopausal women (P less than 0.001), whereas the variables were unchanged with age in men. The correction of WBR for TBBM and UE for BMC increased the validity of the retention methods and the two calculations gave exactly the same results on a group basis, both demonstrating significantly higher bone turnover in women than in men in each age group (P less than 0.05-P less than 0.001). All the turnover variables were measured in a group of perimenopausal women (n = 33). The data clearly demonstrated that bone turnover is menopause dependent, whereas age in itself is of minor significance.

Adult↗

Combined radionuclide and radiocontrast arthrography for evaluating hip arthroplasty.

Twenty-two patients had combined radiographic and radiocolloid arthrography. The two procedures were in agreement in 86% of the patients as to whether the femoral component was loose or not. Fourteen patients has surgical revision of the prosthesis and in 3 (23%) radiographic arthrography was falsely negative. No false negative results were obtained with radiocolloid arthrography thus far. The radionuclide method cannot be used to assess the acetabular component.

Colloids↗

Lymphoscintigraphy.

Lymphoscintigraphy has been used as a noninvasive means of evaluating lymph node involvement. The potential exists for its wider application to other malignancies. Additionally, it is useful in determining the etiology of edema of the extremities. We report the use of 99mTc-antimony sulfide colloid lymphoscintigraphy to determine the etiology of edema of an extremity in a lymphoma patient.

Antimony↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. IV. Interaction of 99mTc-DMS and 99Tc-DMS complexes with blood serum proteins.

As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals 99mTc-DMS and 99Tc-DMS with blood serum proteins was studied. The interaction of 99mTc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins. After in vitro labelling of human sera with 99mTc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65% +/- 3.2% by gel-filtration chromatography; 72% +/- 4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7% +/- 6.8% and 71% +/- 2.3%, respectively. Distribution of 99mTc-DMS or 99Tc-DMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with 99m-Tc-DMS, while the same analysis was performed with 99Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats. The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of alpha 2-, alpha 1- and beta 1-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes.

Alpha-Globulins↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. I. Subcellular localization of 99mTc-DMS complex in the rat kidney in vivo.

Subcellular distribution of 99mTc-DMS (dimercaptosuccinic acid) complex in the rat kidney has been studied. One hour after IV injection of labelled DMS preparation kidney tissue homogenate was subjected to differential subfractionation to obtain cell organelles. Radioactivity distribution in relation to total radioactivity of kidney homogenate obtained in five repeated experiments was as follows (+/- SD): nuclei 4.56% (+/- 0.7); mitochondria 5.97% (+/- 0.7); microsomes 3.63% (+/- 0.8) and cytosol 30.92% (+/- 1.8). Specific activities expressed as counts/min/mg of protein were 148,520 (+/- 15%), 97,440 (+/- 17.7%) and 76,180 (+/- 29%) for mitochondria, cytosol and microsomes respectively. Specific activity of the nuclei was 230.060 (+/- 27%) counts/min/mg of DNA. These results show without doubt that this renal imaging agent, successfully used in human medicine, penetrates into kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria and to a lesser extent, to both microsomes and nuclei.

Animals↗

Low renal uptake of 99mTc-DMSA in patients with proximal tubular dysfunction.

In nine patients with different types of proximal tubulopathy and a nearly normal glomerular filtration rate a low uptake of 99mTc-DMSA in kidneys was found. The underlying mechanism seems to be an increased urinary excretion of 99mTc-DMSA. This radiopharmaceutical might be used as a marker of proximal tubular dysfunction.

Adolescent↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. II. Subcellular localization of 99Tc-DMS complex in the rat kidney in vivo.

In order to extend and confirm our previous studies of in vivo behaviour of 99mTc-DMS in rat kidney cells, the intracellular localization of 99Tc-DMS complex in rat kidney tissue was examined. Animals were injected IV with 99Tc-DMS solution (37 kbq in 1.0 ml) 2 h before killing. Dissected kidneys were homogenized and submitted to differential centrifugation to obtain organelles. The following radioactivity distribution in relation to the total radioactivity of homogenate was obtained in nine experiments: nuclei 3.30% (+/-1.27), mitochondria 9.48% (+/-2.17), microsomes 7.03% (+/-2.34) and cytosol 57.45% (+/-8.01). The subcellular distribution pattern of 99Tc-DMS was in very good agreement with the pattern of 99Tc-DMS binding to kidney cell organelles obtained by the same procedure. Soluble cytoplasmic proteins binding 99Tc-DMS were excluded from a Sephadex G-25 column with the void volume. Their electrophoretic mobility after agarose gel electrophoresis corresponded to beta-lc- and alpha-2-macroglobulins. The results obtained show unambiguously that the investigated complex penetrates into the kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria, and to a lesser extent to both microsomes and nuclei. In another series of six experiments, isolated kidney cortical tissue was used, the same procedure was repeated and similar results were obtained.

Animals↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. III. Subcellular distribution and interaction of 99Tc-DMS complex with macromolecules in rat kidney homogenates in vitro.

Rat kidney tissue homogenates, incubated in vitro with 99Tc-DMS were subjected to differential centrifugation. Specific radioactivities of subcellular fractions were as follows: cytosol 13,552, microsomes 3,600, mitochondria, 2,707 cpm/mg protein, and nuclei, 2,642 cpm/mg DNA. The cytosol fraction was further analyzed by ion-exchange chromatography on DEAE-Sephadex A-25 column. In this way it was separated into several distinct protein zones, three of them bearing a significant amount of 99Tc-DMS preparation. The highest specific radioactivities of proteins were eluted from the DEAE-Sephadex column with 30 mmol/l and 50-110 mmol/l NaCl solution. Total nucleic acids isolated from purified nuclei, mitochondria and microsomes contained a certain amount of bound 99Tc-DMS complex. Nuclear nucleic acids had the highest specific radioactivity, suggesting that 99Tc-DMS complex penetrates into the nuclei.

Animals↗