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Assessment of the physiologic significance of coronary disease with dipyridamole real-time myocardial contrast echocardiography. Comparison with technetium-99m sestamibi single-photon emission computed tomography and quantitative coronary angiography.

OBJECTIVES: The purposes of this study were to test whether quantitative real-time myocardial contrast echocardiography (RT-MCE) can detect coronary disease during pharmacologic stress and to compare this approach with single-photon emission computed tomography (SPECT). BACKGROUND: Assessing myocardial perfusion during stress is important for the diagnosis and risk stratification of patients with coronary disease. METHOD: Thirty-five patients referred for coronary angiography underwent RT-MCE and technetium-99m methoxyisobutylisonitrile (MIBI) SPECT at baseline and after 0.84 mg/kg dipyridamole. The modalities of RT-MCE and SPECT were analyzed both qualitatively and quantitatively. For this purpose, myocardial flow reserve was calculated from microbubble replenishment curves, and regional MIBI uptake was measured on circumferential profiles. Segments and vascular territories were categorized into five groups with increasing stenosis severity by quantitative coronary angiography. RESULTS: With dipyridamole, beta and A x beta increased in all but the highest stenosis severity group. The increase in beta and A x beta was significantly lower in territories supplied by stenotic arteries than in those supplied by arteries with <50% stenosis. Graded decreases in beta and A x beta reserves were noted with increasing stenosis severity. Using the cutoff value of 2.00 for beta reserve, quantitative RT-MCE correctly identified 97% of the territories supplied by significant stenoses and 82% of those supplied by normal arteries. In contrast, quantitative SPECT correctly identified only 71% of the territories supplied by significant stenoses and 81% of those supplied by normal arteries. CONCLUSIONS: This study shows that RT-MCE, with dipyridamole, can define the presence and severity of coronary disease in a manner that compares favorably with quantitative SPECT.

Adult↗

Ethnic differences in the prognostic value of stress technetium-99m tetrofosmin gated single-photon emission computed tomography myocardial perfusion imaging.

OBJECTIVES: This study was designed to evaluate the differential prognostic value of gated single-photon emission computed tomographic imaging (SPECT) imaging in an ethnically diverse multicenter registry. BACKGROUND: Ethnic minority patient populations have reportedly higher coronary heart disease mortality with greater comorbidity and a clustering of risk factors at a significantly younger age when compared with Caucasian, non-Hispanic patients. Despite our increasingly diverse population, the predictive accuracy of cardiac imaging in ethnic minority patients is ill-defined. METHODS: A total of 7,849 patients were prospectively enrolled in a registry of patients undergoing exercise (44%) or pharmacologic stress (56%) technetium-99m tetrofosmin SPECT. Scans were scored using a 20-segment myocardial model with a 5-point severity index. Multivariable Cox proportional hazards models were employed to assess time to death or myocardial infarction. RESULTS: A total of 1,993 African-American, 464 Hispanic, and 5,258 Caucasian non-Hispanic patients underwent SPECT imaging. African-American and Hispanic patients more often had a history of stroke, peripheral arterial disease, angina, heart failure, diabetes, hypertension, and smoking at a younger age. Moderate or severely abnormal SPECT scans were noted in 21%, 17%, and 13% of African-American, Hispanic, and Caucasian non-Hispanic patients, respectively (p < 0.0001). Cardiovascular death rates were highest for ethnic minority patients (p < 0.0001). Annual rates of ischemic heart disease death ranged from 0.2% to 3.0% for Caucasian non-Hispanic and 0.8% to 6.5% for African-American patients with low-risk to severely abnormal SPECT scans (p < 0.0001). For post-stress ejection fraction <45%, annualized risk-adjusted death rates were 2.7% for Caucasian non-Hispanic patients versus 8.0% and 14.0% for African-American and Hispanic patients (p < 0.0001). CONCLUSIONS: The current results from a large observational registry reveal that exercise and pharmacologic stress SPECT effectively predicts major cardiovascular events in a large cohort of African-American and Hispanic patients evaluated for suspected myocardial ischemia. These results provide further evidence that ethnic minority patient populations have a worsening outcome related to cardiovascular disease.

Black or African American↗

Evaluation of pulmonary alveolo-capillary permeability in Type 2 diabetes mellitus: using technetium 99mTc-DTPA aerosol scintigraphy and carbon monoxide diffusion capacity.

The thickening of alveolar basement membrane is found in autopsies, along with microvascular pathologies, in Type 1 and 2 diabetes mellitus (DM). To detect the function and permeability of alveolar basement membrane, carbon monoxide diffusion capacity (DLCO) and technetium 99m-diethyltriaminepentaaceticacid ((99m)Tc-DTPA) aerosol scintigraphy methods can be used. The aim of this study was to determine alveolar basement membrane damage using these two methods. Nineteen women and 6 men, nonsmoking, Type 2 DM cases, without any lung and/or heart disease and who had neither anemia nor obesity, made up the patient group. They were compared with six female and nine male healthy cases who had the same characteristics with the diabetes cases. All of the cases DLCO were measured by single-breath method and (99m)Tc-DTPA aerosol scintigraphy was performed. DLCO showed no difference between the two groups. Aerosol scintigraphy was significantly decreased in the diabetic group (P=.01). In cases with >5 years of diabetic duration (P<.01), in cases with glycolized hemoglobin (HbA(1c)) </=8% (P<.05) and >8% (P<.05), and in microangiopathic cases (P<.01), alveolo-capillary permeability was significantly decreased than in the control group. Among the same groups, no significant difference could be detected for DLCO. The permeability of alveolar basement membrane can reduce in respect to diabetes duration and poor metabolic control. According to our investigation, (99m)Tc-DTPA aerosol scintigraphy method is more sensitive than DLCO method for determining these pathologies.

Administration, Inhalation↗

Electrocardiographic prediction of the severity of posterior wall perfusion defects on rest technetium-99m Sestamibi myocardial perfusion imaging.

To identify electrocardiogram (ECG) variables predicting the severity of previous posterior wall myocardial infarction as measured by technetium-99m-Sestamibi rest single-photon emission computed tomography, we assessed agreement between ECG criteria and posterior wall perfusion defects (PWPDs) in 236 patients. Established ECG criteria for posterior and posterolateral infarctions were present in 22% and 19% of patients, respectively, and did not predict severity of PWPD ( P = NS). Univariate predictors of severity were the Selvester QRS score (SQS) ( P = .001) and an upright T wave in V 1 (UTV 1 ) greater than 0.2 mV ( P = .001). Regression analysis demonstrated that SQS ( P = .0001) and UTV 1 greater than 0.2 mV ( P = .006) were highly predictive of severity ( c statistic = 0.793). All severe PWPDs had an SQS of 2 or higher. Established ECG patterns for diagnosis of posterior infarction are insensitive and poor predictors of severity. The SQS and UTV 1 are effective for the diagnosis of posterior infarction and useful for the estimation of infarct severity.

Coronary Circulation↗

Influence of microorganisms on the behavior of technetium and other elements in paddy soil surface water.

Insolubilization patterns of technetium (Tc) and other trace elements (Sc, Co, Zn, Se, Rb, Sr, Y, Nb, Ce, Pm, Gd, Lu, Hf, and Re) in surface water covering paddy fields were compared to gain insight into the behavior of Tc in an agricultural environment. The insolubilization of Tc, which did not pass through a 0.2-microm-pore-size filter, was mainly caused by bacteria. Among the 14 other elements investigated, Nb was insolubilized by bacteria and the amounts of insoluble Nb were positively correlated with those of Tc. Although Re is a chemical analog of Tc, no similarity was observed. These results suggest that Tc behaves similarly to Nb in the insolubilization in surface water covering paddy fields.

Bacteria↗

Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection.

Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid (99mTc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99mTc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor.

Adult↗

Biphenyls labeled with technetium 99m for imaging beta-amyloid plaques in the brain.

Formation and accumulation of excess aggregates of beta-amyloid (Abeta) plaques in the brain are critical factors contributing to the development and progression of Alzheimer's disease (AD). There is an urgent need for in vivo imaging agents that can specifically demonstrate the location and density of Abeta plaques in the brain. The aim of this study was to develop potential technetium 99m (99mTc)-labeled diagnostic imaging agents specific for the detection of Abeta plaques. Based on previously obtained Abeta plaque-specific biphenyls containing a p-N, N-dimethylaminophenyl group, a series of 99mTc and Re-N2S2-biphenyl derivatives was prepared. The stable neutral and lipophilic 99mTc complexes, [99mTc]19 and [99mTc]23, A+B, were successfully obtained. As surrogates for the 99mTc complexes, the corresponding surrogates, Re complexes of 23, were also prepared. Surprisingly, it was found that the Re complexes showed distinctively different retention profiles as compared with the corresponding 99mTc complexes. Biodistribution studies indicated that [99mTc]23A readily passed through the blood-brain barrier (1.18% dose/brain at 2 min) in contrast to the low brain penetration of [99mTc]19 (0.29% dose/brain at 2 min). Initial results suggested that [99mTc]23A showed selective binding to the Abeta plaque-like structures in the brain sections from transgenic mice but not in the postmortem human brain tissue of patients with confirmed AD. The results provide encouraging evidence that development of a 99mTc-labeled agent for imaging Abeta plaques in the brain may be feasible. Caution should be taken when comparing these 99mTc complexes with the corresponding surrogates--the Re complexes.

Alzheimer Disease↗

Construction of a novel chimera consisting of a chelator-containing Tat peptide conjugated to a morpholino antisense oligomer for technetium-99m labeling and accelerating cellular kinetics.

The attempt to target the limited copies of messenger RNA (mRNA) in vivo with radiolabeled nucleobase oligomers as antisense probes is challenging. Selecting an antisense molecule with superior properties, enhancing the cellular kinetics, and improving the radiolabeling chemistry would be the reasonable approach to accomplish this goal. The present study reports a method to construct a chimera of phosphorodiamidate morpholino nucleobase oligomer (MORF) covalently conjugated to a peptide containing a cell membrane transduction Tat peptide and an N(2)S(2) chelator for technetium-99m ((99m)Tc) radiolabeling (N(2)S(2)-Tat-MORF). The radiolabeling properties and cellular kinetics of (99m)Tc-N(2)S(2)-Tat-MORF were measured. As hypothesized, the preparation of (99m)Tc-N(2)S(2)-Tat-MORF could be achieved by an instant one-step method with labeling efficiency greater than 95%, and the (99m)Tc-N(2)S(2)-Tat-MORF showed distinct properties in cell culture from those of a control, the same MORF sequence without Tat but with mercaptoacetyltriglycine (MAG(3)) as chelator for (99m)Tc ((99m)Tc-MAG(3)-MORF). (99m)Tc-N(2)S(2)-Tat-MORF achieved maximum accumulation of about 35% within 2 h, while (99m)Tc-MAG(3)-MORF showed lower and steadily increasing accumulations but of less than 1% in 24 h. These preliminary results demonstrated that the proposed chimera has properties for easy labeling, and (99m)Tc-N(2)S(2)-Tat-MORF prepared by this method possesses enhanced cellular kinetics and merits further investigation for in vivo mRNA targeting.

Chelating Agents↗

Neutrophil labeling with [(99m)Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide.

INTRODUCTION: [(99m)Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. METHODS: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. RESULTS: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. CONCLUSIONS: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

CD11b Antigen↗

Advances in the production, processing and microPET image quality of technetium-94m.

This work involves the production, processing and imaging of the short-lived, rarely used positron emission tomography (PET) radionuclide technetium-94m (94mTc). Our procedures are an extension of methods reported in the literature and are detailed within. A key modification was the development of a single step that combines purification and concentration of an aqueous 94mTc-pertechnetate solution, which both reduces processing time and increases the final concentration of the solution. Additionally, a convenient method for the direct recovery of 94mTc into an organic solvent was developed, eliminating the solvent transfer step needed for organic syntheses using 94mTc. Each of these advances potentially extends the scope of syntheses possible with this short-lived radionuclide. To explore the imaging potential of 94mTc, we carried out phantom imaging studies on small-scale high-resolution PET scanners to estimate the limitations of detection associated with 94mTc and PET. Preliminary studies demonstrate that useful images can be obtained with modern image reconstruction algorithms when using a correction for the cascade gamma ray contamination.

Isotope Labeling↗

Preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) is useful for judging the safety of hepatic resection.

BACKGROUND: For hepatic resection, the preoperative estimation of hepatic functional reserve in the predicted remnant liver may be more important than that of the entire liver. We evaluated the maximal removal rate of technetium-99m-galactosyl-human serum albumin (GSA-Rmax) in the remnant. METHODS: One hundred and seventy-eight patients were admitted for elective hepatectomy. Conventional liver function, and 15-minute retention rate of indocyanine green (ICGR15) were carried out preoperatively. The GSA-Rmax was calculated according to a radiopharmacokinetic model; then we used the single photon emission computed tomography images to calculate the regional GSA-Rmax in the predicted residual liver (GSA-RL), depending on the operative procedures. The volume of the predicted residual liver (LV-RL) was calculated on the basis of computed tomography images. RESULTS: The preoperative LV-RL correlated well with the GSA-RL in patients with normal liver; however, there was no such correlation in those with chronic hepatitis or cirrhosis. All of 7 postoperative hyperbilirubinemia occurred in the patients with GSA-RL < 0.15. Two patients died of postoperative liver failure 1 to 2 months after the operation. These 2 patients had GSA-RL values of 0.078 and 0.090, respectively, and severe discrepancies between the GSA-Rmax in the remnant liver and ICGR15. CONCLUSIONS: We concluded that GSA-RL may be useful for determining the procedure of hepatectomy and that the value should be maintained at greater than 0.15 to avoid postoperative hyperbilirubinemia or hepatic failure.

Adult↗

Radionuclide imaging for hyperparathyroidism (HPT): which is the best technetium-99m sestamibi modality?

BACKGROUND: To determine the utility of available radionuclide imaging modalities for preoperative parathyroid localization, we compared the accuracy of 4 types of technetium-99m ((99)Tc) sestamibi-based scans. METHODS: Over 5 years, 833 patients with sporadic primary hyperparathyroidism underwent either (99)Tc-sestamibi with planar views (Planar; n = 138); sestamibi single photon emission computed tomography (SPECT; n = 165); SPECT with thyroid (123)I-subtraction phase (SPECT/(123)I; n = 350); or SPECT combined with conventional CT (SPECT/CT; n = 180). The accuracy of each modality was determined on the basis of intraoperative parathyroid pathology, defined as single adenoma or multigland disease. RESULTS: Planar scans had significantly more false negatives (no tumor visualized) than SPECT-based scans (P < 0.01), but positive predictive values were similar. A false-negative scan was present in 38% of Planar scans, 27% SPECT, 4% SPECT/(123)I, and 17% SPECT/CT, with single adenoma found at operation in 77%, 64%, 53%, and 74%, respectively. When a scan had a single focus of uptake, SA was found at that location in 77%, 85%, 68%, and 87%, respectively. SPECT, SPECT/(123)I, and SPECT/CT did not significantly reduce the false-positive rate. CONCLUSIONS: We recommend obtaining multiplanar SPECT-based imaging, which offers 3-dimensional localization and improved detection of parathyroid tumors when compared with Planar scans. A negative scan did not predict multigland disease.

Humans↗

Renal allograft accumulation of technetium-99m sulfur colloid as a predictor of graft rejection.

Differentiation between rejection (the most common cause) and many other possibilities for detrimental effects on graft function represents a difficult issue to diagnose the cause of renal allograft dysfunction. This study was designed to determine whether technetium-99m sulfur colloid (TSC) accumulation predicted graft rejection. We prospectively studied 54 episodes of allograft dysfunction in 53 kidney transplant recipients who underwent TSC scintiscanning and graft biopsy. Visual analysis of TSC uptake compared uptake, in the allograft with that in the marrow of the fifth lumbar vertebra (L5). A 3+ result meant that allograft uptake was greater than L5 marrow uptake; 2+, the same; 1+, less and finally 0, no allograft uptake. Transplant accumulation of 2+ or more was considered consistent with rejection (P = .01). Allograft biopsies interpreted based on the Banff Working Classification showed rejection in 45 of 54 renal biopsies with 42 the biopsy-proven rejection episodes showing at least 2+ graft uptake. Furthermore, this nuclear medicine technique had a sensitivity of 93.3%, a specificity of 44.4%, a positive predictive value of 89.3%, a negative value of 57.1% and an efficiency of 83.3% for the diagnosis of renal allograft rejection.

Adult↗

Removal of dissolved rhenium by sorption onto organic polymers: study of rhenium as an analogue of radioactive technetium.

Technetium (99Tc) is one of the main components of nuclear wastes. Tc characteristics can be predicted by studying rhenium (75Re), one of its chemical analogue, thus avoiding the use of a radioactive element at high concentrations. The objectives of this experimental study was to understand the sorption behavior of Re with natural organic materials in order to define the possible condition of Tc uptake in case where Tc may be transferred into surface or ground waters. As the well-defined organic sorbents we chose chitosan which contains amine -NH2 groups; poly-galacturonic acid (PGA) and poly-styrene sulfonates (PSS) which contain respectively carboxyl -COOH and sulfonate -SO3H groups. Concerning the reaction of Re with PGA or with PSS, no interaction between Re and carboxyl or sulfonate groups was found within the detection limit of this study. Re sorption on chitosan was found to be dependent on ionic strength and pH. We propose that non-specific sorption of perrhenate ion ReO4- via electrostatic interaction takes place at the protonated amine groups NH3+. The polymer-solution interface can be described by the electric diffuse double layer model combined with the Langmuir-Freundlich model. The calculation is in good agreement with our experimental results.

Adsorption↗

Technetium 99m sestamibi in the assessment of acute myocardial infarction.

Technetium 99m sestamibi is a promising new radiopharmaceutical that can assess myocardium at risk, infarct size, and treatment efficacy in acute myocardial infarction. The minimal redistribution of this radiopharmaceutical makes it ideal for the measurement of myocardium at risk, as demonstrated by several animal studies. The high-count density images are readily quantitated, and techniques have been developed and validated for this purpose. Early clinical studies have shown that myocardium at risk varies widely, even for a coronary occlusion in a similar location, a finding similar to that reported previously in several different animal infarction models. The clinical use of this radiopharmaceutical to measure final infarct size and treatment benefit, or myocardial salvage, has now been demonstrated using both planar and tomographic imaging techniques. Evidence of benefit is often evident by 18 to 48 hours after reperfusion therapy, although the full extent of improvement is not evident until later. The current 6-hour shelf life and 30-minute preparation time are logistical barriers to widespread clinical use. This radiopharmaceutical provides a new, powerful measurement tool for the assessment of treatment efficacy in acute myocardial infarction that is probably superior to other currently available methods.

Heart↗

Technetium-99m (99mTc) mercaptoacetyltriglycine: update on the new 99mTc renal tubular function agent.

Technetium-99m (99mTc) mercaptoacetyltriglycine (MAG3) is a new renal radiopharmaceutical that was recently introduced as a 99mTc-labeled replacement for iodine-131 (131I) o-iodohippurate (OIH). Since its introduction, a wide variety of in vitro and in vivo studies have been performed to characterize the high-performance liquid chromatography (HPLC)-purified complex and kit formulations. [99mTc]MAG3 has a slower plasma clearance, a higher plasma protein binding, less red blood cell (RBC) penetration, a lower extraction ratio, and a smaller volume of distribution than OIH. Because of the slower plasma clearance, [99mTc] MAG3 cannot be used as a direct measurement of effective renal plasma flow. Simplified methods have been developed to calculate [99mTc]MAG3 clearances, as well as regression equations to convert these clearances to an equivalent OIH value. The image quality of [99mTc]MAG3 is superior to [131I]OIH; the renogram curves and the fraction of the dose of the two agents that appears in the urine are almost identical, even though the plasma clearance of [99mTc]MAG3 is only 50% to 65% that of OIH. [99mTc]MAG3 compares favorably with OIH in patients with a wide range of clinical problems. The radiation dose to a patient with normal renal function using standard imaging doses is higher for [99mTc]MAG3 than for [131I]OIH, but in patients with impaired renal function, the radiation dose from [131I]OIH is much higher than [99mTc]MAG3. [99mTc]MAG3 also provides superior image quality compared with [99mTc]diethylenetriaminepentaacetic acid (DTPA) in patients with impaired renal function, but it is important to note that [99mTc]MAG3 cannot be used to measure the glomerular filtration rate (GFR). [99mTc]MAG3 is the most promising 99mTc tubular function agent to date, and it has replaced OIH and [99mTc]DPTA in a number of institutions. However, there are physiologic differences between these three agents and, therefore, they should not be expected to behave identically in all clinical conditions.

Animals↗

Imaging of colorectal carcinoma with technetium-99m radiolabeled Fab' fragments.

In this phase III study, patients who had previously undergone surgery for colorectal cancer were studied using a technetium-99m (99mTc)-labeled anti CEA antibody (IMMU-4 [Immunomedics, Morris Plains, NJ] 1mg of protein) to evaluate recurrence. Total-body, planar, and single photon emission computed tomography (SPECT) images were performed within 6 hours of injection. Objectives were to evaluate the efficacy of the 99mTc-labeled anti-CEA antibody, to assess sensitivity and specificity of the agent in known lesions, and to detect occult disease. The impact of antibody study on subsequent surgery was also evaluated. The Fab' fragment has a molecular weight of 54,000 and is supplied as a lyophilized kit that can be instantaneously labeled with 20 to 30 mCi of [99mTc]pertechnetate. In 9 patients with known disease, planar spot imaging identified lesions in 7 (78% sensitivity), SPECT imaging detected lesions in 8 (88% sensitivity), and 1 patient did not have SPECT. In the group of 10 patients with occult (or equivocal) disease, planar imaging sensitivity was 50%, and SPECT sensitivity was 100%. Analysis by site showed 14 of 24 lesions detected by planar imaging (58% sensitivity), and SPECT detected 24 of 24 lesions (100% sensitivity). Tumors as small as .5 cm were visualized in the 19 patients studied. The surgeon judged the antibody study to be impact neutral in 73% of the cases and helpful in 27% of the cases when antibody study altered the presurgical plan.

Colorectal Neoplasms↗

Infection imaging with technetium-99m-labeled chemotactic peptide analogs.

The localization of occult sites of infection is frequently essential to the therapeutic management of critically ill patients. Current imaging procedures, including computed tomography, ultrasound, magnetic resonance imaging, and conventional radiography, rely primarily on focal changes in tissue density or composition to define the lesion. Typically, these are relatively late changes in the inflammatory process. Radionuclide procedures which have been used to localize early inflammatory processes, require a minimum of 12 hours, and usually 24 to 48 hours, from the time of injection to imaging. Clearly, a method of rapidly localizing sites of acute inflammation would be helpful for patient management. Recently, we developed methods for preparing analogs of the leukocyte chemoattractant peptide, N-formyl-methionyl-leucyl-phenylalanine (ForMLF), that can be radiolabeled for external imaging. In vitro, these compounds have bioactivity and neutrophil ForMLF receptor binding comparable with that of the native peptide. Studies in animals demonstrate that these agents bind to leucocytes in vivo, clear from the circulation rapidly, and localize at sites of Escherichia coli infection to an extent sufficient to yield external images early after injection. However, even at relatively low doses, the peptides elicit a profound but transient reduction in peripheral leukocyte levels. Despite this, if the peptides could be radiolabeled at very high specific activity, imaging might be possible with doses of peptide that do not reduce peripheral leukocyte levels. Recently, hydrazino nicotinamide--derivatized peptides were prepared and radiolabeled with technetium-99m at extremely high specific activity (> 20,000 mCi/mumole). In a rabbit model of E coli infection, these peptides yielded excellent images of sites of infection at injected doses that are approximately 1,000-fold below the level that produces a significant reduction in peripheral leukocytes. In addition, studies of thermally injured infected animals indicate that peptide localization may be infection selective, with very low levels of accumulation at sites of sterile inflammation.

Animals↗