Pharmacokinetics of 99mTc-MAA- and 99mTc-HSA-Microspheres Used in Preradioembolization Dosimetry: Influence on the Liver-Lung Shunt.

UNLABELLED: Perfusion scintigraphy using (99m)Tc-labeled albumin aggregates is mandatory before hepatic radioembolization with (90)Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, (99m)Tc-MAA (macroaggregated serum albumin [MAA]) and (99m)Tc-HSA (human serum albumin [HSA]), was assessed. METHODS: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver-lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). RESULTS: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. CONCLUSION: Compared with (99m)Tc-MAA-microspheres, (99m)Tc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.

99mTc-besilesomab (Scintimun) in peripheral osteomyelitis: comparison with 99mTc-labelled white blood cells.

PURPOSE: The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun) with (99m)Tc-labelled white blood cells in patients with peripheral osteomyelitis. METHODS: A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received (99m)Tc-besilesomab and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. RESULTS: The agreement in diagnosis across all three readers between Scintimun and (99m)Tc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun had higher sensitivity than (99m)Tc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). CONCLUSION: Scintimun imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to (99m)Tc-HMPAO-labelled WBCs.

Blinded-read of bone scintigraphy: the impact on diagnosis and healing time for stress injuries with emphasis on the foot.

AIM: This study evaluated the use of bone scintigraphy (BS) for the diagnosis of stress fractures in athletes and its validity for the prediction of healing time, with a focus on foot injuries. METHODS: In our retrospective study, 84 athletes with a total of 93 suspected stress fractures (foot, n = 66; others, n = 27) were included. A blinded-read of BS was performed by 3 observers. The standard of reference was established by an interdisciplinary truth-panel using all imaging data (scintigraphic, radiographic, and magnetic resonance imaging) and follow-up data (>12 month). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing stress fractures were calculated. Stress injuries were rated according to a 5-point grading score (0-4) and associated to the healing time. RESULTS: For the diagnosis of stress injuries (n = 50/93), mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 97.3%, 67.4%, 77.7%, 95.6%, and 83.5%, respectively. Interobserver analysis showed a high agreement between all 3 readers (mean κ = 0.83). In univariate analysis healing time of grade 3 to 4 stress injuries was significantly higher (median, 87 days; interquartile range, 69-132 days) compared with grade 1 to 2 lesions (median, 63 days; interquartile range, 43-95 days; P = 0.0067). Moreover, healing time of scintigraphic high grade stress injuries was significantly longer in a general linear model with adjustment for cofactors (grade, 3-4 vs. 1-2; P = 0.033). CONCLUSIONS: BS is a sensitive and reliable method for the diagnosis of stress injuries. In addition, the simplified classification for mild and severe stress injuries allows an estimation of healing time.

Imaging biomarkers as surrogate endpoints for drug development.

The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates--thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of "personalized medicine". A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may--if properly validated--serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's "critical path initiative".

[Noninvasive diagnosis of coronary artery disease]. / Nichtinvasive Diagnostik der koronaren Herzkrankheit.

BACKGROUND: Coronary artery disease (CAD) is one of the most common diseases that accounts for a considerable part of health care reimbursement. Thus, noninvasive diagnosis of CAD is likewise of pivotal importance for medical care today. NONINVASIVE DIAGNOSIS OF CAD: In this review, the authors present the entire spectrum of noninvasive diagnostic methods available for CAD starting with a Ergomedescription and discussion of the simplest and most important clinical approaches (patients' complaints, risk factors, electrocardiogram, and treadmill test). The established imaging modalities for diagnosing CAD (echocardiography, stress echocardiography, and scintigraphy including the SPECT and PET technique) are presented outlining their specific advantages and disadvantages. Finally, the authors discuss the most recent imaging modalities for the diagnosis of CAD (multislice computed tomography [MSCT] and magnetic resonance imaging [MRI]). MSCT allows for performing high-quality noninvasive coronary angiography, whereas MRI enables exact visualization of myocardial function, perfusion, and viability. CONCLUSION: The comprehensive assessment possible with MSCT and MRI and future developments will change the significance and importance of the conventional diagnostic methods for the diagnosis of CAD in the near future.

Myocardial contrast echocardiography for predicting functional recovery after acute myocardial infarction.

UNLABELLED: Myocardial contrast echocardiography (MCE) is a promising diagnostic tool for detecting microvascular integrity. The aim of the study was to investigate the comparative specificity and sensitivity of intravenous MCE, technetium-99m Sestamibi single-photon emission computed tomography (SPECT) and dipyridamole-dobutamine (DIDO) stress echocardiography for predicting functional recovery after coronary revascularization in patients with acute myocardial infarction (AMI). METHODS: In a prospective, observational study, 17 consecutive patients short after AMI who received successful treatment with primary percutaneous coronary angioplasty (PTCA) plus stent-implantation were examined with DIDO (dipyridamole with 0.28 mg/kg over 4 min plus dobutamine up to 10 mcg/kg/min), MCE (10 ml 4 g, 400 mg/ml Levovist intravenously; second harmonic power imaging) within 12-24 h and resting perfusion SPECT within 48-72 h after PTCA. Functional recovery of regional contractile function after 6-month follow-up was the gold standard to assess viability. RESULTS: The rate of agreement between SPECT and MCE was 69% and between SPECT and a positive response to stress echo was 76% for combined DIDO. MCE showed a higher sensitivity (96%) in the identification of viability than SPECT (77%) and combined DIDO alone (79%). Specificity was lower for viability recognition with MCE (58%) compared with SPECT (93%) and DIDO (87%). CONCLUSIONS: The wall motion response during DIDO echocardiography is useful in the prediction of recovery of regional and global ventricular function after revascularization in patients after AMI. Combined intravenous MCE and DIDO is more accurate in the diagnosis of stunned myocardium than Tc-99m-MIBI SPECT alone.