Correlation of CT Angiography and 99mTechnetium-Labeled Red Blood Cell Scintigraphy to Catheter Angiography for Lower Gastrointestinal Bleeding: A Single-Institution Experience.

PURPOSE: To investigate the correlation of computed tomography (CT) angiography and 99mTechnetium-labeled red blood cell (RBC) scintigraphy to catheter angiography (CA) in the management of lower gastrointestinal bleeding (LGIB) while considering potential nephrotoxic effects of iodinated contrast. MATERIALS AND METHODS: From November 2012 to August 2017, 223 CAs performed for LGIB, including massive, ongoing, and obscure bleeding, were retrospectively identified in patients with pre-procedural CT angiography or RBC scintigraphy. Positive correlations and sensitivities were calculated for CT angiography and RBC scintigraphy using CA results as reference. Correlations were then compared while considering certain clinical presentations of LGIB. Contrast dose was compared with maximum creatinine recorded 48-72 hours after. RESULTS: Thirty-eight patients underwent CT angiography; 173 patients underwent RBC scintigraphy; and 12 patients completed both studies. CT angiography had a positive correlation of 67.7% (95% confidence interval [CI]: 57.0, 76.7) and sensitivity of 85.2% (95% CI: 66.3, 95.8), whereas RBC scintigraphy had a positive correlation of 29.3% (95% CI: 27.7, 31.0) and sensitivity of 94.4% (95% CI: 84.6, 98.8). CT angiography had higher positive correlation across all clinical presentations. No dose-toxicity relationship was observed between contrast and renal function (R2: 0.008), nor was there a difference in incidence of contrast-induced nephropathy between CT angiography and RBC scintigraphy (P = .30). CONCLUSIONS: CT angiography has greater positive correlation to CA than RBC scintigraphy for assessing LGIB in active stable as well as hemodynamically unstable LGIB. As such, greater adoption of CT angiography may reduce the number of nontherapeutic CAs performed. Additional contrast associated with CT angiography does not result in increased nephrotoxicity.

Normalisation to blood activity is required for the accurate quantification of Na/I symporter ectopic expression by SPECT/CT in individual subjects.

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used (99m)Tc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to 'noisy', and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy.

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats.

Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.

Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats.

Effects of sucralose sweetener on blood constituents labelled with technetium-99m ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs.

Effect of Zusanli (ST.36) electroacupuncture at two frequencies on the bioavailability of (99m)Tc-sodium pertechnetate and on labeling of blood constituents in rats.

OBJECTIVES: A study was performed on the effects of stimulation at Zusanli-point (ST.36) by electroacupuncture (EA) at two frequencies on the bioavailability of (99m)Tc-sodium pertechnetate (Na(99m)TcO(4)) in rats. METHODS: Forty Wistar rats were divided into four groups: untreated control, treated by manual acupuncture at ST.36 bilaterally, treated by EA at 2 Hz at ST.36 bilaterally, and the same site at 100 Hz bilaterally. Na(99m)TcO(4) (7.4 MBq) was administrated via the ocular-plexus and, 20 minutes before sacrifice, blood was withdrawn for radiolabeling assay (BRL). In the bioavailability analysis, organs and tissues were isolated, their radioactivity determined, and the percentage of injected dose per gram of organ or tissue (%ID/g) and the %ID were calculated for each organ or tissue (%ID/ot). For BRL, the plasma and blood cells isolated, and the fractions also precipitated with 5% trichloroacetic acid to separate the soluble and insoluble fractions; these were assessed as percentage of injected dose (%ID) in blood (%ID/b). RESULTS: The results showed significant differences in the %ID/g in some organs and tissues in comparison with controls; lung (p = 0.0013), spleen (p = 0.0085), pancreas (p = 0.0167), liver (p = 0.0003), stomach (p < 0.0001), small-intestine (p = 0.0181), large-intestine (p = 0.04099), urinary-bladder (p = 0.0271), thyroid (p < 0.0001), muscle (p = 0.0187); %ID/ot in spleen (p = 0.0349); and %ID/b in blood sample (p = 0.0235). In the blood labeling analyses, EA in either frequency significantly increased insoluble fraction/blood cells (p < 0.0001). CONCLUSIONS: These findings suggested that acupuncture procedures at ST.36 could modulate responses in some organs, tissues, and blood in rats. Further rigorous experimental studies to examine the effectiveness in either acupuncture therapy need to be pursued.

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m.

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m ((99m)Tc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with (99m)Tc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with (99m)Tc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with (99m)Tc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with (99m)Tc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract.

Do inhaled carbon nanoparticles translocate directly into the circulation in humans?

RATIONALE: Increased exposure to particulate air pollution (PM(10)) is a risk factor for death and hospitalization with cardiovascular disease. It has been suggested that the nanoparticulate component of PM(10) is capable of translocating into the circulation with the potential for direct effects on the vasculature. OBJECTIVE: The study's aim was to determine the extent to which inhaled technetium-99m ((99m)Tc)-labeled carbon nanoparticles (Technegas) were able to access the systemic circulation. METHODS AND MAIN RESULTS: Ten healthy volunteers inhaled Technegas and blood samples were taken sequentially over the following 6 h. Technegas particles were 4-20 nm in diameter and aggregated to a median particle diameter of approximately 100 nm. Radioactivity was immediately detected in blood, with levels increasing over 60 min. Thin-layer chromatography of whole blood identified a species that moved with the solvent front, corresponding to unbound (99m)Tc-pertechnetate, which was excreted in urine. There was no evidence of particle-bound (99m)Tc at the origin. gamma Camera images demonstrated high levels of Technegas retention (95.6 +/- 1.7% at 6 h) in the lungs, with no accumulation of radioactivity detected over the liver or spleen. CONCLUSIONS: The majority of (99m)Tc-labeled carbon nanoparticles remain within the lung up to 6 h after inhalation. In contrast to previous published studies, thin-layer chromatography did not support the hypothesis that inhaled Technegas carbon nanoparticles pass directly from the lungs into the systemic circulation.

Protection of plasmid DNA by a Ginkgo biloba extract from the effects of stannous chloride and the action on the labeling of blood elements with technetium-99m.

Ginkgo biloba extract (EGb) is a phytotherapeutic agent used for the treatment of ischemic and neurological disorders. Because the action of this important extract is not fully known, assays using different biological systems need to be performed. Red blood cells (RBC) are labeled with technetium-99m (Tc-99m) and used in nuclear medicine. The labeling depends on a reducing agent, usually stannous chloride (SnCl2). We assessed the effect of different concentrations of EGb on the labeling of blood constituents with Tc-99m, as sodium pertechnetate (3.7 MBq), and on the mobility of a plasmid DNA treated with SnCl2 (1.2 microg/ml) at room temperature. Blood was incubated with EGb before the addition of SnCl2 and Tc-99m. Plasma (P) and RBC were separated and precipitated with trichloroacetic acid, and soluble (SF-P and SF-RBC) and insoluble (IF-P and IF-RBC) fractions were isolated. The plasmid was incubated with Egb, SnCl2 or EGb plus SnCl2 and agarose gel electrophoresis was performed. The gel was stained with ethidium bromide and the DNA bands were visualized by fluorescence in an ultraviolet transilluminator system. EGb decreased the labeling of RBC, IF-P and IF-RBC. The supercoiled form of the plasmid was modified by treatment with SnCl2 and protected by 40 mg/ml EGb. The effect of EGb on the tested systems may be due to its chelating action with the stannous ions and/or pertechnetate or to the capability to generate reactive oxygen species that could oxidize the stannous ion.

The clinical utility of nuclear medicine imaging for the detection of occult gastrointestinal haemorrhage.

Acute gastrointestinal bleeding is often intermittent and the bleeding source may be difficult to locate, resulting in delay of potentially life-saving treatment. The aim of this study was to determine the clinical utility of 99mTc labelled red blood cell imaging and [99mTc]pertechnetate (Meckel's scan) imaging in a series of 137 patients admitted over a 5 year period to hospital for management of acute gastrointestinal bleeding. Of the 137 patients, 70 had positive 99mTc red blood cell studies. Eleven of 24 patients who had imaging performed beyond 3 h had positive scans that would otherwise have been missed. Only 47 patients had a definite final diagnosis at the time of hospital discharge, of which six were negative on 99mTc red blood cell imaging. The correct site of bleeding was localized in seven of 21 patients with foregut bleeding, and 15 of 20 patients with colonic bleeding. Endoscopy yielded a diagnosis in 13 of the 47 patients (28%). Eleven patients had Meckel's scans but all were negative. Angiography was diagnostic in one of 17 patients studied. 99mTc red blood cell imaging is a useful test in the management of acute gastrointestinal bleeding. Imaging beyond 3 h may further improve the bleeding detection rate. This test, however, may be an unreliable means of localization of bleeding, particularly in the foregut.

Selective in vitro labeling of white blood cells using 99mTc-labeled liposomes.

We describe a method by which endocytosis-based radiolabeling of WBC is achieved using 99mTc-liposomes of optimal size and charge, and of a composition that assures both in vitro (whole blood) and intracellular stability of the radiopharmaceutical. In our study, excellent in vitro stability of 99mTc-liposomes with 95% labeling efficiency was observed with >90% stability up to 6 h and a minimum of 85% after 24 h of incubation either in normal saline or serum. Total WBC labeling efficiency using 99mTc-liposomes determined by radio-thin layer chromatographic analysis was 30.6 +/- 2.21%, 20.89 +/- 1.31% for monocytes and 9.7 +/- 1.74% for polymorphonuclears. Negligible activity was bound to red blood cells. The procedure did not affect the cell viability and the separation of the free 99mTc-liposomes from the cells was done by centrifugation.

Passage of inhaled particles into the blood circulation in humans.

BACKGROUND: Pollution by particulates has been consistently associated with increased cardiovascular morbidity and mortality. However, the mechanisms responsible for these effects are not well-elucidated. METHODS AND RESULTS: To assess to what extent and how rapidly inhaled pollutant particles pass into the systemic circulation, we measured, in 5 healthy volunteers, the distribution of radioactivity after the inhalation of "Technegas," an aerosol consisting mainly of ultrafine (99m)Technetium-labeled carbon particles (<100 nm). Radioactivity was detected in blood already at 1 minute, reached a maximum between 10 and 20 minutes, and remained at this level up to 60 minutes. Thin layer chromatography of blood showed that in addition to a species corresponding to oxidized (99m)Tc, ie, pertechnetate, there was also a species corresponding to particle-bound (99m)Tc. Gamma camera images showed substantial radioactivity over the liver and other areas of the body. CONCLUSIONS: We conclude that inhaled (99m)Tc-labeled ultrafine carbon particles pass rapidly into the systemic circulation, and this process could account for the well-established, but poorly understood, extrapulmonary effects of air pollution.

Effect of eggplant (Solanum melongena) extract on the in vitro labeling of blood elements with technetium-99m and on the biodistribution of sodium pertechnetate in rats.

The use of eggplant has been suggested to treat different diseases. We studied the effect of eggplant extract on the labeling of red blood cells (RBC) and plasma proteins with technetium-99m (Tc-99m) and on biodistribution of sodium pertechnetate (Tc-99m) in rats. Blood was incubated with an eggplant extract (final concentrations 3.12 to 250.00 mg/ml) for 60 min. Then, stannous chloride (SnCl2) (0.06 or 1.2 microg/ml) and Tc-99m, as sodium pertechnetate, were added. Samples of RBC and plasma (P) were separated and also precipitated and soluble (SF) and insoluble (IF) fractions were isolated. The percent of radioactivity (%ATI) in the fractions was calculated. In the biodistribution study, Wistar rats were treated with eggplant extract (300 mg/ml) for 4 weeks, in drinking water. Tc-99m was administered in the rats, after 90 min they were sacrificed and organs and blood were isolated. When 0.06 microg/ml SnCl2 was used, eggplant extract: i/ inhibited the label of RBC (97.14 +/- 2.01 to 52.21 +/- 3.97%ATI), ii/ decreased the labeling in IF-P from 38.79 +/- 11.73 to 5.49 +/- 2.65%ATI, and iii/ diminished the labeling in IF-RBC from 90.04 +/- 2.65 to 46.17 +/- 9.49%ATI. This inhibitory effect was not observed with SnCl2 1.2 microg/ml. In the biodistribution study, the %ATI: i/ increased in the liver from 2.15 +/- 0.54 to 3.11 +/- 1.29 and ii/ in the other organs the Tc-99m uptake was not modified. The uptake of Tc-99m in red blood cells protein (IF-RBC) decreased from 66.62 +/- 19.67 to 31.66 +/- 8.84%. It is possible to suggest that some components of the eggplant extract present an oxidation power able to alter the fixation of the Tc-99m on the blood elements. Moreover, as eggplant is metabolized in the liver, this fact could justify the alteration of the uptake in this organ.

Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with technetium-99m.

Peumus boldus is used in popular medicine in Brazil. The influence of Peumus boldus on the labeling of red blood cells and plasma proteins with 99mTc was studied. Stannous chloride and 99mTc pertechnetate were incubated with blood and a tincture of Peumus boldus. Aliquots of plasma and blood cells were isolated from the mixture and treated with trichloroacetic acid (TCA). After separation, analysis of the soluble and insoluble fractions showed a rapid uptake of the radioactivity by blood cells in the presence of the drug, whereas there was a slight decrease in the amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma.

Dual-isotope protocol for indium-111 capromab pendetide monoclonal antibody imaging.

OBJECTIVE: A dual-isotope imaging protocol using 99mTc-labeled red blood cells with 111In capromab pendetide monoclonal antibody imaging for detective and localizing nodal metastasis in prostate cancer is described. METHODS: This protocol involves a single SPECT acquisition that is less time consuming and more comfortable for the patient than the currently recommended method, which requires two separate SPECT acquisitions performed on different days. RESULTS: Forty patients were studied with the dual-isotope protocol. Preliminary data suggest increased accuracy compared with the single-isotope technique. CONCLUSION: The dual-isotope technique assures the precise image registration needed for accurate comparison of blood pool and pelvic lymph node activity that is required for confident and accurate image interpretation.

In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements.

In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4), methylenediphosphonic acid (99mTc-MDP) and glucoheptonate acid (99mTc-GHA) to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P) and blood cells (BC) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (SF) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad) in P and BC was determined. The binding of Na 99mTcO4 (%rad) to P was 61.2% (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to BC was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). 99mTc-MDP study presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to BC was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). 99mTc-GHA study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to BC was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance.

In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

In the present study evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na (99m)TcO4), methylenediphosphonic acid (99m)Tc-MDP)) and glucoheptonate acid (99m)Tc-GHA)) to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P) and blood cells (BC) were isolated and precipitated with 5 percent trichloroacetic acid (TCA), and soluble (SF) and isoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with LM-1 radioautographic emulsions and percent radioactivity (percent rad) in P and BC was determined. The binding of Na (99m)TcO4 (percentrad) to P was 61.2 percent (0 h) and 46.0 percent (24 h), and radioautography showed 63.7 percent (0 h) and 43.3 percent (24 h). The binding to BC was 38.8 percent (0 h) and 54.0 percent (24 h), and radioautography showed 36.3 percent (0h) and 56.7 percent (24 h), and radioautography showed 36.3 percent (0 h) and 56.7 percent (24 h). (99m) Tc-MDP study presented 91.1 percent (0 h) to P and 87.2 percent (24 h), and radioautography showed 67.9 percent (0 h) and 67.4 percent (24 h). The binding to BC was 8.9 percent (0 h) and 12.8 percent (24 h), and radioautography showed 32.1 percent (0 h) and 32.6 percent (24 h). (99m)Tc-GHA study was 90.1 percent (0 h) to P and 79.9 percent (24 h), and radioautography showed 67.2 percent (0 h) and 60.1 percent (24 h). The binding to BC was 9.9 percent (0 h) and 20.1 percent (24 h), and radioautography showed 32.8 percent (0 h) and 39.9 percent (24 h). The comparasion of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) qualitatively in accordance.

Restricted postexercise pulmonary diffusion capacity and central blood volume depletion.

Pulmonary diffusion capacity for carbon monoxide (DLCO), regional electrical impedance (Z0), and the distribution of technetium-99m-labeled erythrocytes together with concentration of plasma atrial natriuretic peptide (ANP) were determined before and after a 6-min "all-out" row in nine oarsmen and in six control subjects. Two and one-half hours after exercise in the upright seated position, DLCO was reduced by 6 (-2 to 21; median and range) %, the thoracic-to-thigh electrical impedance ratio (Z0 thorax/Z0 thigh) rose by 14 (-1 to 29) %, paralleled by a 7 (-3 to 11) % decrease and a 3 (-5 to 12) % increase in the thoracic and thigh blood volume, respectively. These responses were associated with a decrease in the plasma ANP concentration from 15 (13-31) to 12 (9-27) pmol/l (P < 0.05). Similarly, in the supine position, Z0 thorax/Z0 thigh increased by 10 (-5 to 28) % when DLCO was reduced 12 (6-26) % (P < 0.05), whereas DLCO remained stable in the control group. The increase in Z0 thorax/Z0 thigh and the corresponding redistribution of the blood volume in both body positions show that approximately one-half of the postexercise reduction of DLCO is explained by a decrease in the pulmonary blood volume. The role of a reduced postexercise central blood volume is underscored by the lower plasma ANP, which aids in upregulating the blood volume after exercise in athletes.

Plasma clearance and biodistribution of oxidatively modified 99mTc-beta-VLDL in rabbits.

The biodistribution and removal from plasma (measured as fractional clearance rate, FCR, per hour) of native and oxidatively modified 99mtechnetium-labeled beta-very low density lipoprotein (99mTc-beta-VLDL) were investigated in hypercholesterolemic (HC) and control (C) three-month old New Zealand rabbits. The intracellular accumulation of beta-VLDL labeled with 99mTc was studied in vitro in THP-1 cells and monocyte-derived macrophages isolated from rabbits. After intravenous injection into C rabbits, copper-oxidized beta-VLDL (99mTc-ox-beta-VLDL) was cleared from the circulation faster (0.362 +/- 0.070/h) than native beta-VLDL (99mTc-nat-beta-VLDL, 0.241 +/- 0.070/h). In contrast, the FCR of 99mTc-ox-beta-VLDL in HC rabbits was lower (0.100 +/- 0.048/h) than that of 99mTc-nat-beta-VLDL (0.163 +/- 0.043/h). The hepatic uptake of radiolabeled lipoproteins was lower in HC rabbits (0.114 +/- 0.071% injected dose/g tissue for 99mTc-nat-beta-VLDL and 0.116 +/- 0.057% injected dose/g tissue for 99mTc-ox-beta-VLDL) than in C rabbits (0.301 +/- 0.113% injected dose/g tissue for 99mTc-nat-beta-VLDL and 0.305 +/- 0.149% injected dose/g tissue for 99mTc-ox-beta-VLDL). The uptake of 99mTc-nat-beta-VLDL and 99mTc-ox-beta-VLDL by atherosclerotic aorta lesions isolated from HC rabbits (99mTc-nat-beta-VLDL: 0.033 +/- 0.012% injected dose/g tissue and 99mTc-ox-beta-VLDL: 0.039 +/- 0.017% injected dose/g tissue) was higher in comparison to that of non-atherosclerotic aortas from C rabbits (99mTc-nat-beta-VLDL: 0.023 +/- 0.010% injected dose/g tissue and 99mTc-ox-beta-VLDL: 0.019 +/- 0.010% injected dose/g tissue). However, 99mTc-nat-beta-VLDL and 99mTc-ox-beta-VLDL were taken up by atherosclerotic lesions at similar rates. In vitro studies showed that both monocyte-derived macrophages isolated from rabbits and THP-1 macrophages significantly internalized more 99mTc-ox-beta-VLDL than 99mTc-nat-beta-VLDL. These results indicate that in cholesterol-fed rabbits 99mTc-ox-beta-VLDL is slowly cleared from plasma and accumulates in atherosclerotic lesions. However, although the extent of in vitro uptake of 99mTc-ox-beta-VLDL by macrophages was high, the in vivo accumulation of this radiolabeled lipoprotein by atherosclerotic lesions did not differ from that of 99mTc-nat-beta-VLDL.