Investigations of a (99m)Tc-labeled bacteriophage as a potential infection-specific imaging agent. (41/140)

Because bacteriophages (phages) have a natural specificity for bacteria, it may be possible to develop radiolabeled phages as infection-specific agents. METHODS: The M13 phage was radiolabeled with (99m)Tc via mercaptoacetyltriglycine and purified by polyethylene glycol precipitation. After radiolabeling, the phage was tested for binding at 1, 5, and 10 min to Escherichia coli strain 2537, E. coli strain 25922, and Staphylococcus aureus strain 29213. The radiolabeled phage was also tested for specificity in mouse models that had received a subcutaneous injection of either live (infection/inflammation model) or heat-inactivated (inflammation model) cultures in a thigh. The labeled phage (10(9) plaque-forming units, 1-3.7 MBq) was administered either within 20 min (to minimize the contribution from inflammation) or 3 h after induction. The animals were killed 3 h later. RESULTS: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline. Binding of the labeled phage to each of the 3 bacterial strains in vitro was immediate, reaching a maximum at 1 min. However, the percentage bound was significantly higher (P = 0.0008) for E. coli 2537 than for either of the other 2 bacteria (84% vs. 41% and 48%). Furthermore, binding to E. coli 2537 was unchanged at 10 min, whereas binding to both E. coli 25922 and S. aureus decreased to 33%. At 3 h in vivo, the ratio of target thigh to normal thigh was significantly higher (P < or = 0.017) in the infection/inflammation model (2 to 2.5 fold) than in the inflammation model (1.5 to 1.8) and therefore suggestive of increased accumulation specific to infection. The difference was slightly more pronounced in animals that received labeled phage at 20 min after inoculation, showing a ratio of 2.3 for infected thigh to normal thigh and a ratio of 1.6 for inflamed thigh to normal thigh. Although absolute uptake was lowest in the infection/inflammation thigh of mice infected with E. coli 2537, this finding was presumably due to the therapeutic effect of the phage on this strain. CONCLUSION: Radiolabeled bacteriophages should be further investigated as potential agents for specific imaging of infection.  (+info)

Radiation dosimetry for technetium-99m-MAG3, technetium-99m-DTPA, and iodine-131-OIH based on human biodistribution studies. (42/140)

Radiation dose estimates were calculated for the renal agents 99mTc-DTPA, 99mTc-MAG3, and 131I-OIH from biodistribution data gathered in groups of healthy human volunteers. Biokinetics were evaluated by Anger camera imaging, blood sampling, and urine collection and counting. Collected data were fit to four- or five-compartmental models using the CONversational Simulation, Analysis, and Modeling (CONSAM) software. Radiation dose estimates were performed using standard MIRD techniques. Average residence times in urinary bladder, kidney, and remainder of the body were used to predict radiation dose equivalents and effective dose equivalents for the three agents. Doses for DTPA and MAG3 were very similar and much lower on a per unit injected activity than OIH. The effective dose equivalents were 3.3 mSv/370 MBq for 99Tc-DTPA, 3.7 mSv/370 MBq for 99mTc-MAG3, and 0.99 mSv/11.1 MBq for 131I-OIH for bladder voiding every 4.8 hr; effective dose equivalents were 2.0 mSv/370 MBq for 99mTc-DTPA, 1.5 mSv/370 MBq for 99mTc-MAG3, and 0.28 mSv/11.1 MBq for 131I-OIH for bladder voiding at 30 min and then every 4.0 hr. Patients should void at the conclusion of the study, as early voiding can reduce the gonadal radiation dose by a factor of 2 to 3.  (+info)

Technetium-99m-L,L-ethylenedicysteine: a renal imaging agent. I. Labeling and evaluation in animals. (43/140)

L,L-ethylenedicysteine (L,L-EC) can be labeled efficiently with 99mTc at pH 12 to obtain a highly pure and very stable tracer agent (99mTc-L,L-EC). The biological behavior of 99mTc-L,L-EC was studied in mice and a baboon. In mice, 99mTc-L,L-EC demonstrated a more rapid urinary excretion and less retention in the kidneys, the liver, the intestines, and the blood than did 99mTc-MAG3 at 10 and 60 min p.i. Urinary excretion decreased in probenecid pretreated mice, which indicates active tubular transport. In the baboon, the renograms for 99mTc-MAG3 and 99mTc-L,L-EC were comparable. Plasma-protein binding of 99mTc-L,L-EC was lower than that of 99mTc-MAG3 while its distribution volume and 1-hr plasma clearance were clearly higher. The promising results of the animal experiments suggest that 99mTc-L,L-ethylenedicysteine may be a useful alternative to 99mTc-MAG3 for renal function studies in humans.  (+info)

Renal transplant hypertension caused by iliac artery stenosis. (44/140)

A captopril renal study performed with both radiohippuran and 99mTc-MAG3 demonstrated the typical changes of a hemodynamically significant renal artery stenosis in a hypertensive renal allograft recipient. Arteriography demonstrated high grade stenosis not of the renal artery but of the iliac artery. After successful angioplasty, the patient's hypertension resolved.  (+info)

An imaging study using laminin peptide 99mTc-YIGSR in mice bearing Ehrlich ascites tumour. (45/140)

BACKGROUND: The YIGSR is a pentapeptide, from the laminin-1 of the beta1 chain, which can mediate cell adhesion and bind the 67 kD laminin receptor. The purpose is to evaluate the usefulness of (99m)Tc-YIGSR, a novel tumour radiotracer, in the receptor imaging of Ehrlich ascites tumour. METHODS: Using S-acetly-NH3-MAG3 as chelate, YIGSR, a pentapeptide from laminin, was tagged with (99m)Tc. (99m)Tc-YIGSR was detected in the tumour group bearing Ehrlich ascites tumour and blocked group. Tumour, normal, inflammatory and blocked groups were imaged. RESULTS: Through reverse phase Sep-Pak C18 chromatogram, it was revealed that YIGSR could conjugate with S-acetly-NH3-MAG3, and be radiolabelled at room temperature and neutral pH with a radiolabelling yield of 62%, and of 4% without chelate. (99m)Tc-YIGSR was rapidly cleared from kidney, then liver. The imaging findings showed tumour tissue accumulated initial radioactivity at fifteen minutes after injection in the tumour group, and the uptake increased to peak at three hours with a tumour/muscle ratio (T/M) of 11.36, then cleared slowly to a T/M of 7.50 at eight hours. The tumour uptake of radiotracer in blocked group was significantly lower with T/M of 4.61 at three hours and 0.89 at eight hours. The T/M was only 3.72 at three hours and 1.29 at eight hours after injection in inflammatory group. Compared with inflammatory group and control obstructive group, the ratio of T/M in tumour group was significantly different (P < 0.001). CONCLUSIONS: Using S-acetly-NH3-MAG3, we radiolabelled YIGSR with (99m)Tc. (99m)Tc-YIGSR possesses many merits of tumour imaging: rapid visualization, high sensitivity and specificity, and satisfactory target/nontarget ratio. Our data suggest (99m)Tc-YIGSR is a promising tumour radiotracer.  (+info)

Uptake kinetics of 99mTc-MAG3-antisense oligonucleotide to PCNA and effect on gene expression in vascular smooth muscle cells. (46/140)

To investigate the feasibility of in vivo imaging study of atherosclerotic plaque and restenosis using antisense probe, we evaluated the uptake kinetics of radiolabeled oligonucleotides to the messenger RNA (mRNA) of proliferating cell nucleus antigen (PCNA) in vascular smooth muscle cells (VSMCs) and the effect on gene expression. METHODS: The antisense oligonucleotide to PCNA was radiolabeled with (99m)Tc through bifunctional chelator mercaptoacetyltriglycine (MAG(3)). The labeling efficiency was assessed by Sephadex G25 chromatography. The radiochemical purity, in vitro stability, and ability of the labeled antisense oligonucleotide to hybridize to its complement were analyzed by Sep-Pak C18 column chromatography. The uptake kinetics of (99m)Tc-labeled antisense oligonucleotide and sense oligonucleotide were studied in VSMCs in log and plateau phases. To study whether the antisense probe can hybridize to a respective sequence on the whole PCNA mRNA strand after radiolabeling, we performed reverse-transcriptase polymerase chain reaction to assay the PCNA mRNA level after the VSMCs had been incubated with the (99m)Tc-labeled antisense oligonucleotide and sense oligonucleotide. RESULTS: The labeling efficiency of (99m)Tc-MAG(3)-antisense oligonucleotide was 60.1% (n = 5), the specific activity was 1,960 kBq/microg, and the radiochemical purity was more than 95% after purification. (99m)Tc-MAG(3)-antisense oligonucleotide was stable in vitro and retained the ability to hybridize with its complementary chain. Antisense oligonucleotide showed significantly higher accumulation than sense oligonucleotide in log phase, with peak values of 15.2% +/- 0.58% and 5.6% +/- 0.42%, respectively (P < 0.05). No significant difference was found between uptake of antisense oligonucleotide and uptake of sense oligonucleotide in plateau phase (P > 0.05), but higher accumulation of antisense oligonucleotide was found in log phase than in plateau phase (P < 0.05). The retention rate of antisense oligonucleotide in log phase was much higher than that of sense oligonucleotide (79.6% +/- 0.96% vs. 59.8% +/- 0.75%, P < 0.05) at 240 min. The 2 probes did not significantly differ in plateau phase (P > 0.05). The efflux of antisense oligonucleotide was obviously slower in log phase than in plateau phase (P < 0.05). Compared with (99m)Tc-MAG(3)-sense oligonucleotide, (99m)Tc-MAG(3)-antisense oligonucleotide could inhibit the expression of PCNA mRNA significantly. CONCLUSION: This in vitro study in VSMCs provided evidence that the (99m)Tc-labeled antisense oligonucleotide to PCNA can be used for in vivo imaging of atherosclerotic plaque and restenosis in further study.  (+info)

Effect of solvent flow rate in mini-column testing of 99mTc-mertiatide. (47/140)

OBJECTIVE: The recommended method for radiochemical purity testing of 99mTc-mertiatide involves the use of a C-18 solid-phase mini-column cartridge. The mertiatide package insert states that the solvents should be "pushed through the cartridge slowly," but a flow rate is not specified. The mini-column cartridge instruction sheet recommends flow rates of 5-10 and 2-10 mL/min for conditioning and for elution, respectively, of the cartridge. The purpose of this study was to evaluate the effect of different flow rates on determining the radiochemical purity of 99mTc-mertiatide. METHODS: Radiochemical purity was tested on 10 consecutive vials of 99mTc-mertiatide prepared for routine clinical use and on 4 vials of 99mTc-mertiatide spiked with 6%-15% free pertechnetate using 3 different flow rates: slow drip (5 mL/min for conditioning and 2 mL/min for elution), fast drip (10 mL/min for conditioning and 10 mL/min for elution), and very fast drip (about 15-20 mL/min for conditioning and about 15-20 mL/min for elution). An infusion pump was used to provide constant flow rates for the first 2 conditions, whereas manual handling, reflecting real-life practice, was used for the third condition. RESULTS: All 3 flow rates yielded essentially identical radiochemical purities for each vial tested (agreement was always within 0.3% for a given vial). The elapsed times for mini-column conditioning, loading, and elution were approximately 15, 5, and 3 min for the slow drip, fast drip, and very fast drip, respectively. CONCLUSION: Faster flow rates for mini-column testing of 99mTc-mertiatide save time (and correspondingly reduce radiation exposure to the worker) without adversely affecting the results of radiochemical purity determinations.  (+info)

RENEX: an expert system for the interpretation of 99mTc-MAG3 scans to detect renal obstruction. (48/140)

A renal expert system (RENEX) has been developed to assist physicians detect renal obstruction in patients undergoing pre- and postfurosemide 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) scans. RENEX uses quantitative parameters extracted from the dynamic renal scan data and heuristic rules in the form of a knowledge base (KB) obtained from expert interpreters to conclude whether a kidney is obstructed. METHODS: Normal limits were established for 47 quantitative parameters extracted from the 99mTc-MAG3 scans of 100 potential renal donors. From these data the domain expert estimated 5 boundary conditions for each parameter: (i) definitely abnormal, (ii) probably abnormal, (iii) equivocal, (iv) probably normal, and (v) definitely normal. A sigmoid-type curve was then generated from these 5 boundary conditions, creating a parameter knowledge library used for converting the value of a prospective patient's individual quantitative parameters to a certainty factor (CF). Sixty heuristic rules were extracted from the domain expert to generate the KB for detecting obstruction. A forward-chaining inference engine was developed using the MYCIN combinatories (an approximation of Bayes theorem) to determine obstruction. A justification engine was implemented, which recorded the sequence of each rule that was fired and the current CF value of all input and output parameters at the time of instantiation to track and justify the logic of the conclusions. The entire system was fine tuned and tested using a pilot group of 32 patients (11 males, 21 females; mean age, 56.8 +/- 17.2 y; 63 kidneys) deemed by an expert panel to have 41 unobstructed kidneys, 13 obstructed kidneys,and 9 equivocal findings. RESULTS: RENEX agreed with the expert panel in 92% (12/13) of the obstructed kidneys, 93% (38/41) of the unobstructed kidneys, and 78% (7/9) of the kidneys interpreted as equivocal for obstructions. Processing time per patient was practically instantaneous using a 3.0-GHz personal computer programmed using interactive data language. CONCLUSION: We have developed a renal expert system for detecting renal obstruction using pre- and postfurosemide 99mTc-MAG3 renal scans, at a standardized expert level. These encouraging preliminary results warrant a prospective study in a large population of patients with and without renal obstruction to establish the diagnostic performance of this system.  (+info)