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Monocytes have been isolated from patient's blood and directly radiolabelled in vitro using a variety of radiopharmaceuticals such as 99mTc-HMPAO, 111In-oxine, 99mTc-colloids and 18F-FDG. Overall, the best labeling results were obtained using 99mTc-HMPAO. The wide availability of 99mTc and of the ligand HMPAO in kit-formulation makes it the most versatile procedure for imaging localized inflammation using in-vitro labeling. Injection of 99mTc-HMPAO labeled monocytes in adult patients has proven safe with an effective dose of 0.011 mSv/Mbq, equivalent to that of 99mTc-HMPAO labeled mixed white blood cells. Furthermore, in a proof of concept studies, in-vitro labeled monocytes were shown to specifically accumulate in the bowels of patients suffering from inflammatory bowel disease as well as in inflamed joints of rheumatoid arthritis patients. Inversely, the decrease in disease activity of inflamed joints of rheumatoid arthritis patients treated by Adalimumab could not be substantiated using 99mTc-HMPAO labelled monocytes suggesting this type of treatment does not reduce monocyte influx. In spite of their wide availability, in-vitro labeling procedures are cumbersome and time-consuming. Furthermore, cell activation may occur during the labeling process and it cannot be excluded that the radiopharmaceuticals used for labelling interfere with ongoing cellular processes. As such, various authors turned towards the development of radiopharmaceuticals for in-vivo labeling of both monocytes and more importantly macrophages, many of which were subsequently validated in animal models. Targets studied in this regard include amongst others the folate receptor, the mannose receptor, the peripheral benzodiazepine receptor as well as more general characteristics of macrophages such as phagocytosis. Various of these novel molecules appear promising and clinical studies using these radiopharmaceuticals are awaited in the near future. Some of these radiopharmaceuticals also reached the clinical stage, respectively the translocating protein targeting radiopharmaceutical 11C-PK11195 and the folate receptor targeting radiopharmaceutical 99mTc-EC20. Uptake of 11C-PK11195 in inflamed joints and sites of atherosclerosis in patients proved to be directly related to the number of peripheral benzodiazepine binding receptors available as well as to the severity of ongoing inflammation. Comparable results were obtained using 99mTc-EC20 in rheumatoid arthritis patients. In spite of these promising results, additional studies are warranted demonstrating that in vivo, quantitative visualization of monocyte trafficking and accumulation of M1 or M2 macrophage subtypes in sites of ongoing inflammation by means of SPECT and PET will contribute to a better understanding of human inflammatory diseases as well as to diagnosis, treatment planning and the development of targeted treatment strategies.

With growing interest in cell-based scintigraphic diagnosis or therapy monitoring, there is an increasing demand for non-invasive observation and quantification of cell trafficking in the preclinical and clinical setting. Monocytes are members of the human mononuclear phagocyte system originating from a myeloid precursor in the bone. Labeled monocytes are being used for investigation of pathogenesis like atherosclerosis and for monitoring of therapeutic intervention in inflammatory diseases like rheumatoid arthritis. Labeling mononuclear cells at high specific activity without affecting their biological functions allows (delayed) non-invasive imaging with g or PET cameras. Monocytes labeled before their final differentiation into macrophages or dendritic cells may reveal centers of inflammation in a patient and, thereby, contribute to scintigraphic diagnosis. Macrophages or dendritic cells may be in vitro cultured and by means of genetic transformation specified towards specific targets prior to re-injection, an approach with therapeutic potency. This review addresses issues on autologous monocytes, particularly their properties and labeling for non-invasive in vivo radionuclide imaging of chronic inflammation.

The purpose of the investigation was to determine the activity of mononuclear phagocytes in inflammatory diseases and atherosclerosis at various predominant sites. The mononuclear phagocytic system was studied using labeled compounds, which determined the functional activity of reticular endothelial elements in all tissues of an organism. The analysis of the results of studying the activity of the mononuclear phagocytic system leads to the conclusion that virtually good agreement of the values of the parameters under study in the groups of patients supports the commonness of the processes of development of inflammatory reactions and atherogenesis.

Background: The association of hyperglycaemia with reduced fluorodeoxyglucose (FDG) uptake by tumour cells is well established. Therefore, it is standard practice that all patients must fast for at least several hours prior to FDG positron emission tomography (PET) imaging. However, the effect of hyperglycaemia on FDG uptake by inflammatory and infectious lesions is unknown. The aim of this study was to investigate this important issue., Methods: For in vitro studies human mononuclear cells were isolated from 12 normal volunteers and FDG uptake was determined in medium containing differing concentrations of glucose. FDG uptake by human mesothelioma cells was also measured for comparison. For studies involving patients, 416 FDG PET scans of patients with confirmed malignancy (n=321) or benign lesions (n=95) were reviewed retrospectively. The relationship between serum glucose level and FDG uptake by the lesions was assessed utilizing the standardized uptake value (SUV) technique., Results: In the in vitro studies, while FDG uptake by mesothelioma cells decreased as glucose concentration increased, there was no differential uptake of FDG uptake by mononuclear cells at glucose concentrations less than 250 mg x dl(-1). In clinical patients, FDG uptake by malignant lesions was slightly, but negatively affected by serum glucose level (r= -0.21, P<0.01) (glucose range 49-187 mg x dl(-1)). In contrast, FDG uptake by inflammatory lesions was positively associated with serum glucose level (r=0.43, P<0.01) (glucose range 54-215 mg x dl(-1))., Discussion and Conclusion: While the degree of FDG uptake is primarily influenced by the nature of the underlying lesion, serum glucose concentration appears to have a small effect on FDG uptake, which differs between malignant disorders and inflammatory processes. Our data suggest that below a certain level, elevated glucose concentration might not have a negative effect on FDG uptake in inflammatory cells, contrary to that observed in malignant disorders.