Detection of pulmonary emboli with 99mTc-labeled anti-D-dimer (DI-80B3)Fab' fragments (ThromboView).

RATIONALE: We report a new method to diagnose acute pulmonary embolism (PE) by single photon emission computerized tomography (SPECT) after administration of (99m)Tc-labeled anti-D-dimer (DI-80B3) monoclonal antibody Fab' fragments. This novel technique provides an additional approach to diagnosing PE in patients for whom other methods are nondiagnostic or contraindicated. OBJECTIVES: We performed a prospective, multicenter study to investigate the sensitivity and specificity of (99m)Tc-DI-80B3/SPECT in patients with suspected acute PE. METHODS: Subjects with a moderate to high clinical probability of PE or a positive D-dimer test underwent a PE-protocol contrast-enhanced multidetector thoracic computed tomography (CT) scan as well as (99m)Tc-DI-80B3/SPECT (0.5 mg (99m)Tc-DI-80B3 intravenously followed by a thoracic SPECT 2.5 h later). Separate and independent adjudication committees, blinded to clinical data and other test results, interpreted the (99m)Tc-DI-80B3/SPECT scans (PE detected as foci of abnormally increased (99m)Tc uptake) and the thoracic CT scans using Prospective Investigation of Pulmonary Embolism Diagnosis II criteria. MEASUREMENTS AND MAIN RESULTS: Of the 52 patients who were enrolled and completed both tests, 42 had both evaluable SPECT scans and thoracic CT scans. Using the criterion standard (thoracic CT scan) there were 21 patients with PE and 21 without. (99m)Tc-DI-80B3/SPECT had a sensitivity of 76.2% (95% confidence interval, 52.8-91.8%) and a specificity of 90.5% (95% confidence interval, 69.8-98.8%). Treatment-related serious adverse events did not occur. CONCLUSIONS: (99m)Tc-DI-80B3/SPECT was sensitive and specific for acute PE in subjects with moderate to high clinical probability of PE or a positive D-dimer test. (99m)Tc-DI-80B3/SPECT demonstrated an acceptable safety profile and avoids exposure to contrast.

Inaccuracies in estimated glomerular filtration rate in one Australian renal centre.

BACKGROUND: Early identification of true renal disease (glomerular filtration rate (GFR) < 60 mL/min) results in better patient outcomes. There is now routine reporting in Australia of estimated GFR (eGFR) in all patients over age 18 who have serum creatinine measured, calculated by the Modification of Diet in Renal Disease (MDRD) formula, which was validated in an American Caucasian cohort. Significant clinical decisions and prognosis are often made on the basis of this calculation. AIM: To assess the accuracy of three estimates of GFR in an Australian population by comparing eGFR obtained by the abbreviated MDRD (aMDRD), Cockcroft-Gault corrected for body surface area (BSA) (CG) and Chronic Kidney Disease Epidemiology (CKD-Epi) formulae with a gold standard, isotopic (51) Cr-ethylenediaminetetra-acetic acid ((51) Cr-EDTA) GFR. METHODS: Patients referred with an eGFR of <60 mL/min reported by the aMDRD formula underwent isotopic measurement of GFR (over 4 h) and had eGFR calculated using CG corrected for BSA, aMDRD and CKD-Epi formulae. Data were analysed using Bland-Altman plots and regression analysis to compare methods; bias, precision and the proportion of patients correctly stratified by stage of chronic kidney disease (CKD) were also compared according to the three estimates of GFR, using (51) Cr-EDTA GFR as the gold standard. RESULTS: A total of 139 patients were recruited (female 45%), mean age 64 years and mean serum creatinine 212 µmol/L. The mean GFR (SD) (mL/min per m(2) ) for isotopic, CG, aMDRD and CKD-Epi were 47 (28), 37 (20), 32 (17) and 33 (18) (P = 0.001). CG (57%) was more likely to correctly stage CKD than aMDRD (37%) or CKD-Epi (37%), and absolute bias was significantly lower using CG than either other method (P = 0.001). CONCLUSION: In this small Australian population the CG formula corrected for BSA agreed more closely with isotopic GFR and correctly staged patients with CKD more often than the aMDRD or CKD-Epi formulae. It is important that each renal Unit considers the accuracy of estimates of GFR according to their population demographics.

Pulmonary emboli imaging with (99m)Tc-labelled anti-D-dimer (DI-80B3) Fab' followed by SPECT.

OBJECTIVES: Pre-clinical experiments demonstrated that intravenous (99m)Tc labelled DI-DD-3B6/22-80B3 humanised anti-fibrin-D-dimer Fab' fragments ((99m)Tc-DI-80B3) allowed scintigraphic imaging of acute pulmonary emboli (PE). The aims of this clinical study were to determine the safety of (99m)Tc-DI-80B3 in patients with PE and evaluate the resulting scintigraphic images for the localisation of acute PE. MATERIALS/PATIENTS AND METHODS: (99m)Tc-DI-80B3 (0.5mg, 710-850MBq) was administered intravenously to subjects (n=14) with segmental or larger PE on recent contrast-enhanced helical CT scans. Thoracic SPECT scans were acquired 15 minutes, 2 hours and 4 hours afterwards. Subjects were followed for 90 days subsequently. RESULTS: There were no serious adverse events or antibody responses associated with (99m)Tc-DI-80B3 administration. Focal accumulations of (99m)Tc-DI-80B3 on the SPECT images of the thorax acquired at four hours corresponded to pulmonary emboli detected by CT. Two independent "blinded" SPECT readers identified 79% and 71% (respectively) of the right lung and 79% and 64% (respectively) of the left lung in which CT scans disclosed PE. CONCLUSIONS: (99m)Tc-DI-80B3 is well-tolerated in patients with acute PE and does not induce an immune response. (99m)Tc-DI-80B3 may offer a novel approach to imaging PE in a clinically acceptable timeframe without exposure to potentially nephrotoxic radiographic contrast agents.

Safety, pharmacokinetic and dosimetry evaluation of the proposed thrombus imaging agent 99mTc-DI-DD-3B6/22-80B3 Fab'.

PURPOSE: (99m)Tc-DI-DD-3B6/22-80B3 (Thromboview, hereafter abbreviated to (99m)Tc-DI-80B3 Fab') is a humanised, radiolabelled monoclonal antibody Fab' fragment with high affinity and specificity for the D-dimer domain of cross-linked fibrin. The purpose of this study was to evaluate the safety, pharmacokinetics and dosimetry of four increasing doses of (99m)Tc-DI-80B3 Fab' in healthy volunteers. METHODS: Thirty-two healthy volunteers (18-70 years; 16 male, 16 female) received a single intravenous injection of 0.5, 1.0, 2.0 or 4.0 mg of (99m)Tc-DI-80B3 Fab'. Safety outcomes (vital signs, electrocardiography, haematology, biochemistry, adverse events and development of human anti-human antibodies) were assessed up to 30 days post injection. Blood and urine samples were collected up to 48 h post injection. Gamma camera images were acquired at 0.5, 1, 2, 4, 6 and 24 h post injection. Dosimetry was performed using standard MIRD methodology. RESULTS: No adverse events considered to be drug related were observed. Human anti-human antibody was not detectable in any subject during the follow-up period. (99m)Tc-DI-80B3 Fab' had a rapid initial plasma clearance (t (1/2)alpha=1 h). The pharmacokinetic profile of the Fab' fragment was generally linear across the four dose cohorts. By 24 h, 30-35% of the administered radioactivity appeared in the urine. There was marked renal accumulation with time, but no specific uptake was identified within other normal tissues. The effective dose was 9 mSv/750 MBq. CONCLUSIONS: (99m)Tc-DI-80B3 Fab' is well tolerated, is rapidly cleared and exhibits clinically acceptable dosimetry-characteristics well suited to a potential thrombus imaging agent.

Exposure to diagnostic ionizing radiation in sports medicine: assessing and monitoring the risk.

OBJECTIVE: To understand the estimation of both the effective dose and the risk estimate associated with diagnostic ionizing radiation in sports medicine and to appreciate strategies by which this radiation exposure may be minimized. DESIGN: Observational study. SETTING: Sports medicine practice. PATIENTS: A theoretical patient, athlete X (male, aged 20-29 years, 80 kg), was used to illustrate how the effective dose and the corresponding risk estimate are calculated for various common sports medicine investigations. Doses and risk estimates for female and pediatric athletes also are discussed. MAIN OUTCOME MEASURES: The effective dose and corresponding risk estimate associated with common sports medicine investigations. RESULTS: Computed tomography and radiographic examinations of the extremities have significantly lower effective doses than investigations about the trunk region. Bone scanning and computed tomography have a significantly higher effective dose than radiography. The risk estimates associated with the low doses used in diagnostic ionizing radiation procedures are extrapolated from epidemiologic studies on exposures to high doses of radiation, and several uncertainties exist in this estimation. Notwithstanding this, the responsible clinician should be aware of both the effective doses and the risk estimates that are associated with the more common investigations. The principles of justification and optimization for these investigations will help guide clinicians to reduce radiation exposure without compromising the management of their patients. CONCLUSIONS: Certain investigations have a greater effective dose and risk estimate than others. Elite athletes may potentially undergo numerous investigations in their career. An athlete radiation record may be useful to better manage this exposure.