Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence.

In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N(3)S system is described and a comparison made with [Tyr(3)]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG(3) and an N(3)S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands for HYNIC conjugates. All conjugates and (99m)Tc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd<5 nM). The biodistribution was markedly dependent on the BFC and co-ligand used, with the amidothiol ligands showing a greater degree of hepatobiliary clearance, the HYNIC/tricine complex higher blood levels and the HYNIC/EDDA complex the highest level of renal excretion and lowest blood levels. All peptide conjugates showed receptor-mediated uptake in tumour xenografts, but tumour uptake was significantly lower for the (99m)Tc-RC160 derivatives compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide (0.2%-3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with (99m)Tc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide, (99m)Tc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives.     

99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide.

In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide. METHODS: HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice. RESULTS: All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for 111In-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whereas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribution profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with 111In-DTPA-octreotide, lower ratios in blood and muscle, but considerably higher tumor-to-kidney ratios. CONCLUSION: TOC can be radiolabeled to high specific activities using HYNIC as a bifunctional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc-EDDA-HYNIC-TOC a promising candidate for an alternative to 111In-DTPA-octreotide for tumor imaging.     

Evaluation of renal function from 99mTc-MAG3 renography without blood sampling.

To develop a camera-based method for evaluating renal function with 99mTc-mercaptoacetyltriglycine (MAG3), we examined the relationship between various renogram parameters and 99mTc-MAG3 clearance. METHODS: Twenty-one patients underwent renal scintigraphy with 99mTc-MAG3. Eighty 3-s frames were obtained after the bolus injection of 250 MBq tracer, followed by the collection of 52 30-s frames. Regions of interest were drawn for the kidneys, perirenal background areas and subrenal background areas, and background-subtracted renograms were generated. Renal accumulation at 0.5-1.5, 0.5-2, 1-2, 1-2.5 and 1.5-2.5 min after tracer arrival in the kidney was calculated as area under the background-subtracted renogram, and percent renal uptake was obtained after correction for soft-tissue attenuation and injected dose. The slope of the renogram was determined for the same segments used in calculating area under the renogram, and slope index was computed as slope corrected for attenuation and injected dose. Percent renal uptakes and slope indices were correlated by linear regression analysis with 99mTc-MAG3 clearance measured using a single blood sampling method. RESULTS: Among the values of percent renal uptake, the value obtained at 1.5-2.5 min using the perirenal background correlated best with 99mTc-MAG3 clearance. The slope index at 0.5-1.5 or 0.5-2 min using the subrenal background provided better accuracy than percent renal uptake for predicting clearance. There were no substantial differences in the relative function of the right kidney between the methods using percent renal uptake and slope index. CONCLUSION: 99mTc-MAG3 clearance can be assessed with acceptable accuracy by a camera-based method. The method based on the slope of the renogram may replace the one based on the area under the renogram in evaluating renal function from 99mTc-MAG3 renograms.     

Tc-99m DTPA diffuse pulmonary uptake in patients with coronary artery disease and renal insufficiency.

Diffuse bilateral lung uptake was observed in 10 patients undergoing Tc-99m DTPA renal scanning, referred for the evaluation of rising serum creatinine levels. All 10 patients demonstrated renal insufficiency (RI) as shown by both decreased bilateral renal tracer concentration and elevated background activity. Nine of the patients were known to have coronary artery disease (CAD) and six of these nine patients were in congestive heart failure (CHF), at or around the time of scanning. However, Tc-99m DTPA lung uptake was not observed in five other patients whose scans demonstrated RI, in whom there was no CAD or other cardiac disease. Diffuse lung uptake of Tc-99m DTPA in patients with RI therefore is highly suggestive of cardiac dysfunction (i.e. CAD and/or CHF).     

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.     

Biokinetics of (99m)Tc-UBI 29-41 in humans

Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. (99m)Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites in mice. The aim of this study was to establish a (99m)Tc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans. Whole-body images from 6 children with suspected bone infection were acquired at 1, 30, 120, 240 min and 24 h after (99m)Tc-UBI administration. Regions of interest (ROIs) were drawn around source organs (heart, liver, kidneys and bladder) on each time frame. The same set of ROIs was used for all 6 scans and the cpm of each ROI were converted to activity using the conjugate view counting method. Counts were corrected by physical decay and by the background correction factor derived from preclinical phantom studies. The image sequence was used to extrapolate (99m)Tc-UBI time-activity curves in each organ and calculate the cumulated activity (A). Urine samples were used to obtain the cumulative percent of injected activity (% I.A.) versus time renal elimination. The absorbed dose in organs was evaluated according to the general equation described in the MIRD formalism. In addition, (67)Ga-citrate images were obtained from all the patients and used as a control. Biokinetic data showed a fast blood clearance with a mean residence time of 0.52 h. Approximately 85% of the injected activity was eliminated by renal clearance 24 h after (99m)Tc-UBI administration. Images showed minimal accumulation in non-target tissues with an average target/non-target ratio of 2.18 +/- 0.74 in positive lesions at 2 h. All infection positive(99m)Tc-UBI images were in agreement with those obtained with (67)Ga-citrate. The mean radiation absorbed dose calculated was 0.13 mGy/MBq for kidneys and the effective dose was 4.34 x 10(-3)mSv/MBq.     

The usefulness of Tc-99m tetrofosmin scintigraphy in the diagnosis and localization of hyperfunctioning parathyroid glands

PURPOSE: The aim of the work was to study the diagnostic value of Tc-99m tetrofosmin to localize anomalous parathyroid glands in patients with hyperparathyroid disease. METHODS: We studied 31 patients, 19 with primary and 12 with secondary hyperparathyroid disease. Five of these patients were renal graft recipients. All patients underwent surgery. Each patient was injected with 555 to 740 MBq (15 to 20 mCi) Tc-99m tetrofosmin. Subsequently, radionuclide images were acquired 15 and 120 minutes after injection using a low-energy, all-purpose, parallel-hole collimator. Pertechnetate thyroid scintigraphy was obtained in nine cases (24 to 48 h later) when the thyroid activity made it difficult to identify the parathyroid glands. RESULTS: All cases showed tracer uptake as early as 15 minutes after injection. In the group of patients with primary hyperparathyroid disease, 15 showed focal uptake in a parathyroid gland, and surgery revealed an adenoma in the same location. In one patient with hyperplasia, scintigraphy identified only two of four diseased glands. In the three remaining cases, scintigraphy showed focal uptake in the lower parathyroid gland, whereas at surgery the abnormal gland was located in the upper pole. In the secondary hyperparathyroidism group, seven patients showed diffuse tracer uptake in two or more glands, and histologic analysis confirmed hyperplasia in all of them. Five cases showed focal uptake, with three evaluated after surgery (uptake in the only remaining gland); one of them was a renal graft recipient, and the remaining patient had chronic renal failure and was receiving hemodialysis. CONCLUSIONS: Our results suggest that Tc-99m tetrofosmin may be a suitable tracer for preoperative detection and screening of anomalous parathyroid glands. The earlier images at 15 minutes were better than those at 120 minutes. Tc-99m tetrofosmin is cleared more slowly from the normal thyroid than is Tc-99m sestamibi, and both of these tracers may give better results than the old pertechnetate TI-201 subtraction technique.     

99Tcm-MAG3 for quantitation of differential renal function

We studied two different methods for the evaluation of differential renal function in a group of 100 patients with various kidney disorders whose effective renal plasma flow (ERPF) had been calculated previously by single 125I-orthoiodohippurate (OIH) injection and multiple blood sampling. Patients were divided into three groups according to their ERPF:ERPF is greater than or equal to 250 ml min-1; ERPF less than or equal to 100 ml min-1; and ERPF greater than 100 ml min-1 and less than 250 ml min-1. The two methods used to assess differential renal function were: first, relative 99Tcm-dimercaptosuccinic acid (DMSA) uptake calculated by normalized background and attenuation corrected cumulative counts in each kidney 24 h p.i.; and second, relative 99Tcm-mercaptoacetyl-triglycine (MAG3) uptake within 1 and 2 min p.i. calculated by normalized background and attenuation corrected counts on each renal area. The results obtained with each method correlated strongly with high significance (p less than 0.0001). In the right kidney, mean values obtained with 99Tcm-MAG3 tend to be higher than mean values obtained with 99Tcm-DMSA.     

Quantitation of differential renal function with Tc-99m MDP

This study was designed to evaluate the usefulness of the bone tracer Tc-99m MDP for quantitative assessment of relative renal function as compared with renal imaging radiotracers used for that purpose. Differential renal function, i.e., the percent contribution each kidney makes to global renal function, was determined prospectively in 15 consecutive patients using Tc-99m MDP and a renal radionuclide tracer, either Tc-99m DTPA or Tc-99m GHA. Differential function was computed in all cases from the early (1-3 minutes) renal uptake of the tracers by region-of-interest analysis of the computer-acquired data. There was a high correlation between values of differential function obtained with Tc-99m MDP and those obtained with Tc-99m DTPA or Tc-99m GHA (r = 0.98, P less than 0.0001). Qualitative assessment of the images revealed equivalent scintigraphic patterns in all patients. It is concluded that the early characteristics of renal handling of Tc-MDP are sufficiently similar to those of Tc-DTPA and Tc-GHA so that accurate estimates of differential renal function are possible with this agent, and that Tc-MDP-determined renal differential most likely reflects differential glomerular filtration rate.     

Structural requirements for in vivo detection of cell death with 99mTc-annexin V.

(99m)Tc-Annexin V is used to image cell death in vivo via high-affinity binding to exposed phosphatidylserine. We investigated how changes in membrane-binding affinity, molecular charge, and method of labeling affected its biodistribution in normal mice and its uptake in apoptotic tissues. METHODS: An endogenous Tc chelation site (Ala-Gly-Gly-Cys-Gly-His) was added to the N-terminus of annexin V to create annexin V-128. The membrane-binding affinity of annexin V-128 was then progressively reduced by 1-4 mutations in calcium-binding sites. In addition, mutations were made in other residues that altered molecular charge without altering membrane-binding affinity. All mutant proteins were labeled with (99m)Tc at the same N-terminal endogenous chelation site. Wild-type annexin V was also labeled with (99m)Tc after derivatization with hydrazinonicotinamide (HYNIC). Radiolabeled proteins were tested for biodistribution in normal mice and in mice treated to induce apoptosis of the liver. RESULTS: Comparison of (99m)Tc-annexin V-128 with (99m)Tc-HYNIC-annexin V showed that the protein labeled at the endogenous chelation site had the same or higher uptake in apoptotic tissues, while showing 88% lower renal uptake at 60 min after injection. The blood clearance of annexin V was unaffected by changes in either the membrane-binding affinity or the molecular charge. Kidney uptake was unaffected by changes in binding affinity. In marked contrast, uptake in normal liver and spleen decreased markedly as affinity decreased. The same pattern was observed in animals treated with cycloheximide to induce apoptosis. Control experiments with charge mutants showed that the effects seen with the affinity mutants were not due to the concomitant change in molecular charge that occurs in these mutants. CONCLUSION: (a) All four domains of annexin V are required for optimal uptake in apoptotic tissues; molecules with only 1 or 2 active domains are unlikely to be suitable for imaging of cell death in vivo. (b) Uptake in normal liver and spleen is specific (dependent on phosphatidylserine-binding affinity), whereas renal uptake is nonspecific. (c) (99m)Tc-Annexin V-128 detects cell death as well as (99m)Tc-HYNIC-annexin V, while showing 88% less renal retention of radioactivity due to much more rapid urinary excretion of radioactivity.     

Indication for different mechanisms of kidney uptake of radiolabeled peptides.

Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. METHODS: Male Wistar rats (4 per group) were injected intravenously with 1 MBq of (111)In-labeled octreotide (OCT), minigastrin (MG), bombesin (BOM), or exendin (EX), together with a potential inhibitor of renal uptake (lysine [Lys], poly-glutamic acid [PGA], and Gelofusine [GF], a gelatin-based plasma expander) or phosphate-buffered saline as a control. Organ uptake at 20 h after injection was determined as the percentage of injected activity per gram (%IA/g). Lys, PGA, and GF were also combined to determine whether an additive effect could be obtained. The localization of the peptides in the kidneys was investigated by autoradiography using a phosphor imager. RESULTS: OCT accumulation in the kidney was inhibited by Lys and GF (40.7%-45.1%), whereas PGA was ineffective. On the other hand, renal uptake of BOM, MG, and EX was inhibited by PGA and GF (15.4%-85.4%), whereas Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting OCT uptake, whereas PGA and GF had additive effects for the inhibition of EX uptake. The amount of kidney uptake correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex, as indicated by autoradiography. CONCLUSION: Inhibition of renal accumulation of the radiopeptides tested could be achieved by either Lys or PGA but not by both at the same time, suggesting 2 different uptake mechanisms. The differences in renal accumulation of radiopeptides may be related to the number of charges of a molecule. GF is the only compound that inhibited renal accumulation of all radiopeptides tested. Additional experiments are needed to further elucidate these findings and to optimize inhibition of renal accumulation of radiopeptides to reduce the kidney dose in PRRT.     

Quantitation of absolute and relative renal uptake using 99mTc-DMSA: sequential change in time and correlation with 99mTc-DTPA uptake

A renal uptake of 99mTc-DMSA as a function of time and correlation between 99mTc-DMSA and 99mTc-DTPA in renal uptake were discussed. The absolute renal uptake of 99mTc-DMSA calculated by complete correction of tissue attenuation and physical decay showed increase by 5 hours after the administration, except one case with congestive heart failure. The net renal counts attained a maximum between 2 to 3 hours after the administration. There was a good correlation (r -0.992, p less than 0.001) between the relative renal uptake of 99mTc-DMSA (2 hour) and that of 99mTc-DTPA (2-3 min). On the contrary, the absolute renal uptake of 99mTc-DMSA as a indicator of total renal function showed a poor correlation (r = 0.419) to GFR calculated from 99mTc-DTPA. The results indicate that the relative renal uptake of 99mTc-DMSA is a reliable quantitative parameter for split renal function. However, the absolute renal uptake of 99mTc-DMSA may be suggested to be a different renal functioning indicator from GFR calculated from 99mTc-DTPA.     

Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence

In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N₃S system is described and a comparison made with [Tyr³]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG₃ and an N₃S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N’-diacetic adic (EDDA) as co-ligands for HYNIC conjugates. All conjugates and ^99mTc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd<5 nM). The biodistribution was markedly dependent on the BFC and co-ligand used, with the amidothiol ligands showing a greater degree of hepatobiliary clearance, the HYNIC/tricine complex higher blood levels and the HYNIC/EDDA complex the highest level of renal excretion and lowest blood levels. All peptide conjugates showed receptor-mediated uptake in tumour xenografts, but tumour uptake was significantly lower for the ^99mTc-RC160 derivatives compared with ^99mTc-EDDA/HYNIC-[Tyr³]-octreotide (0.2%–3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with ^99mTc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with ^99mTc-EDDA/HYNIC-[Tyr³]-octreotide, ^99mTc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives. Received 26 January and in revised form 16 April 1999     

A comparison of the renal handling of 99Tcm-DTPA and 99Tcm-MAG3 in hypertensive patients using an uptake technique.

The renal uptake and outflow of 99Tcm-DTPA and 99Tcm-MAG3 were compared by analysing renal studies performed in two different departments, but with analysis techniques and computer programs using algorithms that were almost identical. Comparison was performed by a retrospective review of results from patients who were referred for renal investigations because of hypertension but who had apparently normal kidneys. The analysis of tracer outflow rates in the form of whole-kidney transit times and renal cortical transit times showed no significant difference between the two tracers. The fractional uptake rate of tracer for each patient (both kidneys) indicated that MAG3 was extracted from the blood 3.3 times faster than DTPA in patients aged 20-69 years, with a lower ratio above the age of 70. When used to measure relative renal function, there was no overall difference between the two tracers. The fractional uptake rates were also converted to flow rates, producing values of 95.8 +/- 28.0 ml.min(-1).1.73 m-2 for DTPA and 320 +/- 75 ml.min(-1).1.73 m-2 for MAG3, in hypertensive patients aged 20-40 years. These values showed a good correlation with other published GFR and MAG3 clearance rates (obtained using blood sampling methods) in normal patients of similar ages.     

Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry.

Renal uptake of Tl-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of Tl-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For Tl-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for Tl-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for Tl-201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter-renal regions as background; however, paraspinal uptake was relatively higher with Tl-201 (P less than 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with Tl-201 (P = 0.06). Measurements with Tl-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P less than 0.01), reflecting the qualitative impression. Thus, ancillary Tl-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy.     

Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected for renal size

BACKGROUND: Decreased relative 99mTc dimercaptosuccinic acid (99mTc-DMSA) uptake can be a consequence of abnormal kidney size, associated with normal or impaired function. When there is a small kidney, relative 99mTc-DMSA uptake is decreased, and it is sometimes difficult to distinguish a small, normal kidney from a hypofunctioning kidney. Here, relative renal function was studied by quantifying the relative 99mTc-DMSA uptake corrected for renal size (RCU). METHODS: Five hundred and fifty-five consecutive patients (184 adults) aged 1 month to 82 years (mean, 14.8 years) underwent a 99mTc-DMSA study for various renal diseases. Results were compared with the relative 99mTc-DMSA uptake without size correction (RUU). Visual evaluation of images was also performed. RESULTS: In 288 patients (52%) the relative 99mTc-DMSA uptake was normal, either uncorrected or corrected, for renal size; in 184 (33%) it was abnormal by both quantification methods; and in 83 (15%) it was abnormal only by one method. Two hundred and fifty-seven patients (46%) presented with decreased RUU in one kidney, associated with a small kidney in 73 patients (13%). RCU was normal in all of these 73 patients (100%, P<0.0001). The sensitivity and specificity of RCU for evaluating renal function in relation to small renal size and with respect to RUU were 72% and 97%, with positive and negative predictive values of 95% and 80%, and an accuracy of 85%. Visual analysis of the 73 studies with decreased RUU and normal RCU showed a small, normal kidney on 55 occasions (75%), cortical scars in eight (11%), and impaired bilateral function in 10 (14%). Visual analysis of 10 studies with normal RUU and decreased RCU showed dilated pyelocalyceal system in seven occasions (70%) and normal kidneys in three (P<0.0001). CONCLUSION: It is concluded that relative 99mTc-DMSA uptake corrected for renal size is a more accurate method for assessing individual renal function. When there is a small kidney, relative 99mTc-DMSA uptake corrected for renal size can distinguish between a normal and a hypofunctioning kidney.     

Methods for measuring the renal uptake rate of 99mTc-dimercaptosuccinic acid (DMSA): a comparative study

A comparative study of the renal uptake rate of 99mTc-dimercaptosuccinic acid (DMSA) was performed using a phantom study and clinical data from 100 patients (200 kidneys) with a variety of renal diseases. The measurement methods for renal uptake rate studied here include a posterior-view method, a conjugate-view method, and a method using single photon emission computed tomography (SPECT). The renal uptake rates obtained by the posterior-view method significantly (P less than 0.001) depended on kidney depth correction. With the SPECT method, the cut-off level for delineating the kidney was changed according to the background count ratio using the results of the phantom study. The renal uptake rates obtained by the SPECT method correlated significantly (P less than 0.001) with those obtained by other methods, and there were no significant differences as compared with those obtained by the conjugate-view method. An analysis of error with the above methods indicated that the error relating to the sensitivity to body thickness was smallest for the SPECT method and greatest for the posterior-view method. In terms of measurement of renal uptake rate only, the conjugate-view method is considered the most useful because it needs no kidney depth correction and requires very little additional effort or examination time.     

Preparation of technetium-99-DMS renal complex in solution and its chemical and biological characterization

99Tc-DMS solution was prepared by double isotope labelling, purified by molecular sieving through Sepharose 2B column, and checked by chromatographic and spectrophotometric methods, as well as by assessment of its biodistribution in rats. The preparations, obtained in a series of nine experiments, showed high renal uptake (30-40% of injected dose per organ) and could be used for further investigations of Tc-DMS biochemical behaviour in kidney tissue at subcellular level. Radioactive concentrations of purified 99Tc-DNS preparations were 37-74 kBq/ml and absorption maxima at 412-425 nm (yellow complex). By application of 99mTc, 99Tc-DMS preparation in rats, good renal scans have been obtained.     

Nuclear imaging analysis of human low-density lipoprotein biodistribution in rabbits and monkeys

We have evaluated the biodistribution of human low-density lipoprotein (LDL) radiolabeled with 99mTc or with 123I-tyramine cellobiose in rabbits and in rhesus monkeys. Biodistribution was assessed after intravenous injection of radiolabeled LDL by quantitative analysis of scintigrams, counting of excreta, and counting of tissues at necropsy. Both rabbits and monkeys showed lower renal uptake (123I:99mTc approximately 1:3, as regional percent injected activity corrected for physical decay) and excretion (1:2 to 1:4), but higher hepatic (1.5:1 to 2:1) and cardiac (1.7:1 to 4:1) uptake of 123I than of 99mTc. Adrenals were visualized in normolipemic animals with 123I-tyramine cellobiose-LDL but not with 99mTc-LDL. Hyperlipemic animals showed increased cardiac (up to six-fold) and decreased hepatic activity (by 50%-60%) of both radionuclides. We conclude that 123I-tyramine cellobiose-LDL is better suited than 99mTc-LDL for dynamic studies of LDL metabolism in vivo.     

99Tcm-(tin) colloid scans in the evaluation of renal transplant rejection

Technetium-99m-(tin) colloid uptake in renal transplants was quantified to evaluate rejection. A dynamic acquisition following i.v. injection of 110 MBq of this radiopharmaceutical enabled quantification of 15 to 20 min transplant uptake (PU), in terms of percentage of an injected dose after allowing for attenuation in the patient. An uptake ratio (UR) i.e. the ratio of 15 to 20 min uptake over the 0 to 5 min uptake was also derived. Normal values were obtained in 20 stable functioning transplants (normal PU less than or equal to 1%, normal UR less than or equal to 0.7). In 66 patients, PU and UR were compared with clinical, biochemical, histological and radiological, evidence of rejection. A sensitivity of 70% and specificity of 85% was obtained for this 99Tcm-(tin) colloid study in the diagnosis of renal transplant rejection.