Granulocyte-colony-stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral-blood CD34؉ cells without mobilization in six patients with AMI. After large-volume cytapheresis and positive CD34 ؉ cell selection, 3.6 to 27.6 million CD34؉ cells were obtained. We performed intracoronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial-labeled CD34 ؉ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34 ؉ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18 F]-fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment. STEM CELLS 2006;24:333-336

In cancer vaccination trials, antigen-loaded dendritic cells (DCs) are usually injected intradermally and are expected to rapidly move to a regional lymph node where antigen presentation should occur. In this study we investigated the influence of indium-111 oxine (111In) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelling on the motility and actin content of antigen-loaded DCs in parallel with in vivo migration in humans. Human autologous monocyte-derived DCs loaded with a tumour antigen were labelled with 111In (0.11, 0.37 or 0.74 MBq/10(7) DCs) or 99mTc-HMPAO (18.5 or 185 MBq/10(7) DCs). 111In labelling was much more stable than 99mTc-HMPAO labelling. Quantitative videomicroscopy showed that the mean distance of displacement of DCs increased in accordance with the 111In activity used for labelling. Monomeric (G) and filamentous (F) actin content of DCs evaluated by quantitative immunofluorescence demonstrated that the ratio of filamentous to globular actin content in labelled DCs increased significantly in accordance with the activity used for labelling with both tracers. Twelve patients enrolled in a phase I/II vaccination trial received injections of 10(7) antigen-loaded DCs labelled with either 0.74 MBq of 111In (group A, n=6/12) or 18.5 MBq of 99mTc-HMPAO (group B, n=6/12) in the proximal part of the legs, one intradermally on one side, one subcutaneously on the opposite side. In three of the six patients of each group, antigen-loaded DCs were incubated with monophosphoryl lipid A (MPL) just before the labelling, in order to initiate the maturation process (subgroup MPL+). Only one MPL+ patient of group A exhibited faint focal uptake in the inguinal region on the late images. Group B presented a more complex pattern of radioactivity distribution (early bladder activity without brain uptake) indicating that 99mTc-HMPAO is not a suitable radiopharmaceutical for labelling of loaded DCs. The activity cleared from DCs as a labelled molecule different from the lipophilic 99mTc-HMPAO. Only one of the six patients had nodular inguinal uptake on the intradermally injected side (DCs not incubated with MPL). In conclusion, the present study did not demonstrate migration of loaded labelled DCs from intradermal or subcutaneous sites of injection to regional lymph nodes. This provides an indication that a large proportion of antigen-loaded DCs, as used in current human trials for cancer therapy, may not reach regional lymph nodes.

In a canine model of chronic myocardial infarction, bone marrow mononuclear cell transfer is superior to mesenchymal stem cell transfer in improvement of cardiac contractility and regional systolic function and reduction in infarct size and plasma N-terminal B-type natriuretic propeptide level. Functional improvement is associated with a favorable angiogenic environment and neovascularization.

The aim of this study was to re-examine, by retrospective analysis of our case material, the specificity and sensitivity of technetium-99m ciprofloxacin scan in discriminating between infection and other conditions. (99m)Tc-ciprofloxacin scintigraphy was performed in 71 patients: 30 patients referred for suspicion of osteomyelitis (OM) or septic arthritis (SA) (group 1) and 41 controls (group 2). Imaging was performed at 4 h post injection and, when possible, at 8 or 24 h post injection. Tracer uptake was visually assessed in different joint groups, and in the sites suspicious for infection. Several soft tissue sites were also evaluated. In the group referred for osteo-articular infection, we found a lower specificity (54.5%) than has previously been reported in the literature. Evaluation of tracer uptake at late imaging did not improve discrimination between sterile and non-sterile inflammation. Additionally, articular uptake was seen in many control patients. Infecton uptake in growth cartilage, thyroid gland, vascular pool, lungs, liver and intestines is discussed.

MET-PET/CT appears a reliable technique to guide MAS of parathyroid glands.

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.

Transcoronary transplantation of progenitor cells has been proposed as a novel therapy for ischemic heart failure. The primary aims were to assess the feasibility of obtaining CD34+ cells from blood without mobilization in chronic conditions and to compare homing with results reported in acute conditions. We also evaluated the effect of CD34+ on endothelial function. In 7 patients with a history of an anterior myocardial infarction (20 +/- 2 months), a large amount of CD34 (18.2 +/- 3.0 x 10(6)) were obtained and an intracoronary infusion into the left anterior descending artery via an over-the-wire balloon catheter was performed. Myocardial homing involved 3.2% +/- 0.6% of injected cells. Endothelial function studied with increasing doses of bradykinin was not significantly modified after 3 months. In the treated group, compared with 5 nonrandomized control patients with a similar clinical history, the only echocardiographic significant change (2-way analysis of variance) was a decrease in end-systolic volume (P < 0.03). In conclusion, large amounts of CD34+ cells can be obtained from blood, without mobilization, in the chronic phase of myocardial infarction. As reported in the acute situation 1 hour after treatment, intracoronary infusion of CD34+ cells results in myocardial homing of a few percents of the cells. In this small group of patients, no effect of this therapy is detected on the endothelial function and only marginal changes are observed on echocardiographic parameters.

Tools for evaluation of disease activity in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) include scoring clinical manifestations, determination of biochemical parameters of inflammation, and obtaining tissue biopsies. These tools, however, are sometimes inconclusive. 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET) scans are commonly used to detect inflammatory or malignant lesions. Our objective is to explore the ability of PET scanning to assess the extent of disease activity in patients with AAV.Consecutive PET scans made between December 2006 and March 2014 in Maastricht (MUMC) and between July 2008 and June 2013 in Brussels (EUH) to assess disease activity in patients with AAV were retrospectively included. Scans were re-examined and quantitatively scored using maximum standard uptake values (SUVmax). PET findings were compared with C-reactive protein (CRP) and ANCA positivity at the time of scanning.Forty-four scans were performed in 33 patients during a period of suspected active disease. All but 2 scans showed PET-positive sites, most commonly the nasopharynx (n = 22) and the lung (n = 22). Forty-one clinically occult lesions were found, including the thyroid gland (n = 4 patients), aorta (n = 8), and bone marrow (n = 7). The amount of hotspots, but not the highest observed SUVmax value, was higher if CRP levels were elevated. Seventeen follow-up scans were made in 13 patients and showed decreased SUVmax values.FDG PET scans in AAV patients with active disease show positive findings in multiple sites of the body even when biochemical parameters are inconclusive, including sites clinically unsuspected and difficult to assess otherwise.