SPECT/CT imaging of inflammation and calcification in human carotid atherosclerosis to identify the plaque at risk of rupture.

BACKGROUND: Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers. METHODS: Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology. RESULTS: On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype. CONCLUSION: Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.

Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111In-DANBIRT.

BACKGROUND: 111In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated 111In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. METHODS AND RESULTS: ApoE-/- mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of 111In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with 111In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with 111In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111In-DANBIRT uptake and CD68 and LFA-1 expressing cells. CONCLUSIONS: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation.

International guidance on the establishment of quality assurance programmes for radioactivity measurement in nuclear medicine.

A new guidance document for the implementation of quality assurance (QA) programmes for nuclear medicine radioactivity measurement, produced by the International Atomic Energy Agency, is described. The proposed programme is based on the principles of ISO 17025 and will enable laboratories, particularly in developing countries, to provide consistent, safe and effective radioactivity measurement services to the nuclear medicine community.

Problems associated with the clinical use of radiopharmaceuticals: a proposed classification system and troubleshooting guide.

Problems associated with the clinical use of radiopharmaceuticals can usually be classified into one of four categories: unusual imaging results, adverse reactions, unique difficulties encountered in special patient populations, and quality assurance failures. Each of these problem areas is briefly described and a guide for troubleshooting such problems is presented.

Clinical radiopharmacy: principles and practices.

On the average, radiopharmacists spend about 17.2% of their time in clinical activities if their practice setting is in an institution, and about 8.5% of their time if their practice setting is in a centralized nuclear pharmacy. A recent survey of radiopharmacists was conducted to determine: (1) the percentage of time they spend engaged in selected activities, and (2) the specific clinical activities in which they are involved. A few radiopharmacists spend as much as 50% of their time in clinical activities, but most spend only 5% to 20% of their time. Some of the clinical activities involve direct interactions with patients, such as explaining the reasons for administering the radioactive material or actually administering the dose. Other clinical activities are indirect, such as reviewing charts before or after studies and making recommendations to other health care professionals. About half of the pharmacists surveyed see a need for increasing their clinical activities. The need to maximize the time involved in providing pharmaceutical care is discussed and several patient-care activities/responsibilities are proposed.