18F-Fluorocholine PET/CT Is More Sensitive Than 11C-Methionine PET/CT for the Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.

Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18F-fluorocholine (18F-FCH) PET/CT compared with 11C-methionine (11C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99mTc-sestaMIBI (99mTc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99mTc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11C-MET and 18F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11C-MET PET/CT. 18F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18F-FCH and 60% and 94%, respectively, for 11C-MET (P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18F-FCH and 52% and 94%, respectively, for 11C-MET (P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99mTc-MIBI SPECT findings, 18F-FCH PET/CT performs better than 11C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients.

Positron emission tomography scanning in anti-neutrophil cytoplasmic antibodies-associated vasculitis.

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-[F]-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.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

CONTEXT: Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. OBJECTIVE: To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. DESIGN AND SETTING: Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. RESULTS: Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. CONCLUSIONS: MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Colonoscopic Findings in Patients With Incidental Colonic Focal FDG Uptake.

OBJECTIVE: The purpose of this study was to investigate the nature of FDG-avid and non-FDG-avid lesions detected at colonoscopy in patients presenting with incidental focal colonic FDG uptake at PET/CT. MATERIALS AND METHODS: Among 9073 patients who underwent PET/CT over a 4-year period, 82 patients without a history of colonic disease had focal colonic FDG uptake and underwent colonoscopy. In consensus, a radiologist and a nuclear physician read images from these PET/CT examinations. They recorded the location of focal FDG uptake in the colon and associated CT abnormalities and measured maximum standardized uptake value (SUVmax) and metabolic volume (MV). Readings were performed twice--first without and second with knowledge of lesion location at colonoscopy. The final diagnosis was based on colonoscopic findings and histopathologic results categorized into benign, premalignant, or malignant. RESULTS: One hundred seven foci of colonic FDG uptake at PET/CT and 150 lesions at colonoscopy were detected. Among 107 foci of FDG uptake, 65 (61%) corresponded to a lesion at colonoscopy (true-positive findings), and 42 (39%) did not (false-positive findings). Among 150 lesions found at colonoscopy, 85 (57%) were not FDG avid (false-negative findings). The MV of true-positive findings was lower than that of false-positive findings (4.0 ± 0.4 cm(3) vs 6.2 ± 0.7 cm(3); p = 0.006), but SUVmax did not differ (7.4 ± 0.5 vs 7.7 ± 0.5; p = 0.649). Considering the histopathologic categories of the lesions and the false-positive findings, there was no difference in SUVmax (p = 0.103), but MV was lower in premalignant lesions than in false-positive findings (p = 0.005). CONCLUSION: Focal colonic FDG uptake may indicate the presence of a benign, pre-malignant, or malignant lesion. Subsequent colonoscopy should not be restricted to the colonic site of FDG uptake.

MR imaging versus PET/CT for evaluation of pancreatic lesions.

PURPOSE: To retrospectively determine the diagnostic accuracy of magnetic resonance imaging (MRI) and combined positron emission tomography/computed tomography (PET/CT) in the differential diagnosis of benign and malignant pancreatic lesions. MATERIALS AND METHODS: Twenty-seven patients (15 women/12 men, mean age 56.5 years) with MR imaging and PET/CT studies performed to differentiate benign and malignant pancreatic lesions were identified between October 2008 and October 2010. Both MR and PET/CT data sets were retrospectively and blindly evaluated by two independent readers (4 readers total) with different degrees of experience, using a visual five-point score system. The results were correlated with final diagnosis obtained by histopathology. RESULTS: 17 patients had malignant diseases and 10 patients had benign diseases. Depending on the observer, the sensitivity, specificity, positive predictive value and negative predictive value of MRI varied between 88-94%, 50-80%, 75-89% and 71-89% respectively. Sensitivities, specificities, positive predictive values and negative predictive values of PET/CT were 73%, 56%, 73% and 56% respectively. The diagnostic accuracy of MR for the differential diagnosis of pancreatic lesions was 74-89%, compared with 67% for PET/CT. The weighted Cohen's kappa coefficient was 0.47 at MR and 0.53 at PET/CT. CONCLUSION: MRI achieved higher sensitivity and specificity in the differential diagnosis of pancreatic lesions.

Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction.

OBJECTIVE: Stem cell therapy can facilitate cardiac repair in infarcted myocardium, but the optimal cell type remains uncertain. We conducted a randomized, blind, and placebo-controlled comparison of autologous bone marrow mononuclear cell and mesenchymal stem cell therapy in a large-animal model of chronic myocardial infarction. METHODS: Eleven weeks after coronary ligation, 24 dogs received intramyocardial injections of mononuclear cells (227.106 +/- 32.106 cells), mesenchymal stem cells (232.106 +/- 40.106 cells), or placebo (n = 8 per group). Cardiac performance and remodeling were assessed up to 16 weeks' follow-up. RESULTS: At echocardiographic analysis, the wall motion score index showed a sustained improvement after mononuclear cell transfer (from 1.8 +/- 0.1 to 1.5 +/- 0.07) and a moderate late improvement after mesenchymal stem cell transfer (from 1.9 +/- 0.08 to 1.7 +/- 0.1). After mononuclear cell transfer, end-systolic elastance increased (from 2.23 +/- 0.25 to 4.42 +/- 0.55 mm Hg/mL), infarct size decreased (from 13% +/- 0.67% to 10% +/- 1.17%), N-terminal B-type natriuretic propeptide level decreased (from 608 +/- 146 to 353 +/- 118 pmol/L), and relative wall area and arterial density increased. Vascular endothelial growth factor receptor 2 expression was upregulated in the border zone. No change in cardiac contractility or histologic parameters was noted in the mesenchymal stem cell group. CONCLUSION: 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.

Myocardial homing and coronary endothelial function after autologous blood CD34+ progenitor cells intracoronary injection in the chronic phase of myocardial infarction.

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.

Accurate pre-operative localization of pathological parathyroid glands using 11C-methionine PET/CT.

OBJECTIVE: The pre-operative technique most routinely used to localize pathological parathyroid glands (PPG), prior to minimal access surgery (MAS), relies on 99mTc-sestamibi (MIBI) scintigraphy. Positron emission tomography (PET) using the radiolabelled amino acid 11C-methionine as the tracer agent offers a technological alternative to localize PPG. In this study we evaluated the sensitivity of 11C-methionine PET/CT (MET-PET/CT) for PPG detection and the extent to which MET-PET/CT images may contribute to the planning of surgical procedures. DESIGN: Thirty patients were included, 22 with primary hyperparathyroidism and eight with secondary hyperparathyroidism. Patients suspected of suffering from parathyroid hyperplasia underwent a complete surgical exploration of the neck region. In those suspected of parathyroid adenoma, surgery was limited to the presumed localization described by MET-PET/CT. To specifically address the additional benefit of the MET-PET/CT in terms of surgical planning and procedure, the surgeon classified the patients into two categories depending on the type of benefit, or the reason for the absence of benefit, occurring in each case. We also compared the sensitivity of MET-PET/CT and MIBI scintigraphy. RESULTS: The total number of lesions removed was 46 (24 adenomatous and 22 hyperplastic). Globally, MET-PET/CT provided additional benefit to surgery in 15 out of 30 cases (50%). The sensitivity of 11C-methionine PET/CT and MIBI scintigraphy was respectively 92% and 95% for adenoma, and 68% and 59% for hyperplasia, on the basis of available resected lesions. CONCLUSION: MET-PET/CT appears a reliable technique to guide MAS of parathyroid glands.

Therapeutic efficacy of antitumor dendritic cell vaccinations correlates with persistent Th1 responses, high intratumor CD8+ T cell recruitment and low relative regulatory T cell infiltration.

Despite the increasing number of immunotherapeutic strategies for the treatment of cancer, most approaches have failed to correlate the induction of an anti-tumor immune response with therapeutic efficacy. We therefore took advantage of a successful vaccination strategy-combining dendritic cells and irradiated GM-CSF secreting tumor cells-to compare the immune response induced against 9L gliosarcoma tumors in cured rats versus those with progressively growing tumors. At the systemic level, the tumor specific cytotoxic responses were quite heterogeneous in uncured vaccinated rats, and were surprisingly often high in animals with rapidly-growing tumors. IFN-gamma secretion by activated splenic T cells was more discriminative as the CD4+ T cell-mediated production was weak in uncured rats whereas high in cured ones. At the tumor level, regressing tumors were strongly infiltrated by CD8+ T cells, which demonstrated lytic capacities as high as their splenic counterparts. In contrast, progressing tumors were weakly infiltrated by T cells showing impaired cytotoxic activities. Proportionately to the T cell infiltrate, the expression of Foxp3 was increased in progressive tumors suggesting inhibition by regulatory T cells. In conclusion, the main difference between cured and uncured vaccinated animals does not depend directly upon the induction of systemic cytotoxic responses. Rather the persistence of higher CD4+ Th1 responses, a high intratumoral recruitment of functional CD8+ T cells, and a low proportion of regulatory T cells correlate with tumor rejection.

Pharmacoscintigraphic and pharmacokinetic evaluation of tobramycin DPI formulations in cystic fibrosis patients.

Tobramycin dry powder formulations were evaluated by gamma scintigraphy and pharmacokinetic methods. In an open single-dose, three-treatment, three-period, cross-over study, nine cystic fibrosis patients received both the two test products and the reference product Tobi (nebulizer solution) in order to assess lung deposition and systemic comparative bioavailability of the two investigational inhaled products versus the marketed inhaled comparator product. The percentage of dose (mean+/-SD) in the whole lung was 53.0+/-10.0% for the tobramycin Form 1, 34.1+/-12.4% for the tobramycin Form 2 and 7.6+/-2.7% for the comparator product Tobi. Lung deposition expressed as a percentage of the nominal dose was thus estimated to be 7.0 and 4.5 times higher for the Tobra Form 1 and Tobra Form 2 than for the Tobi, respectively. Furthermore, the systemic bioavailability (adjusted to correspond to the same drug dose as that of the comparator product deposited in the lung) was found to be 1.6 times higher for the comparator product Tobi than for the two DPI formulations. The principal advantages of the DPI formulations include reduced systemic availability and thus, side effects, and higher dose levels of the drug at the site of drug action.

Bidirectional MHC molecule exchange between migratory and resident dendritic cells.

Dendritic cells (DCs) loaded extracorporeally with antigen can be used as an adjuvant in vivo. In this work, we analyzed the migration of transferred DC and monitored the phenotype of new migrants in the draining lymph nodes. It is surprising that we found that a majority of resident DCs expressed donor MHC molecules and that a proportion of injected DCs acquired host MHC molecules. These observations suggest that a bidirectional MHC molecule exchange occurs between migratory and resident DCs, a mechanism that may amplify antigen presentation in vivo.

Assessment of pretest probability of pulmonary embolism in the emergency department by physicians in training using the Wells model.

INTRODUCTION: Assessment of pretest probability should be the initial step in investigation of patients with suspected pulmonary embolism (PE). In teaching hospitals physicians in training are often the first physicians to evaluate patients. OBJECTIVE: To evaluate the accuracy of pretest probability assessment of PE by physicians in training using the Wells clinical model and to assess the safety of a diagnostic strategy including pretest probability assessment. PATIENTS AND METHODS: 291 consecutive outpatients with clinical suspicion of PE were categorized as having a low, moderate or high pretest probability of PE by physicians in training who could take supervising physicians' advice when they deemed necessary. Then, patients were managed according to a sequential diagnostic algorithm including D-dimer testing, lung scan, leg compression ultrasonography and helical computed tomography. Patients in whom PE was deemed absent were followed up for 3 months. RESULTS: 34 patients (18%) had PE. Prevalence of PE in the low, moderate and high pretest probability groups categorized by physicians in training alone was 3% (95% confidence interval (CI): 1% to 9%), 31% (95% CI: 22% to 42%) and 100% (95% CI: 61% to 100%) respectively. One of the 152 untreated patients (0.7%, 95% CI: 0.1% to 3.6%) developed a thromboembolic event during the 3-month follow-up period. CONCLUSION: Physicians in training can use the Wells clinical model to determine pretest probability of PE. A diagnostic strategy including the use of this model by physicians in training with access to supervising physicians' advice appears to be safe.

Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients.

UNLABELLED: The aim of this study was to assess the feasibility and the potential role of PET/CT with (18)F-FDG-labeled autologous leukocytes in the diagnosis and localization of infectious lesions. METHODS: Twenty-one consecutive patients with suspected or documented infection were prospectively evaluated with whole-body PET/CT 3 h after injection of autologous (18)F-FDG-labeled leukocytes. Two experienced nuclear medicine physicians who were unaware of the clinical end-diagnosis reviewed all PET/CT studies. A visual score (0-3)-according to uptake intensity-was used to assess studies. The results of PET/CT with (18)F-FDG-labeled white blood cell ((18)F-FDG-WBC) assessment were compared with histologic or biologic diagnosis in 15 patients and with clinical end-diagnosis after complete clinical work-up in 6 patients. RESULTS: Nine patients had fever of unknown etiology, 6 patients had documented infection but with unknown extension of the infectious disease, 4 patients had a documented infection with unfavorable evolution, and 2 patients had a documented infection with known extension. The best trade-off between sensitivity and specificity was obtained when a visual score of >or=2 was chosen to identify increased tracer uptake as infection. With this threshold, sensitivity, specificity, and accuracy were each 86% on a patient-per-patient basis and 91%, 85%, and 90% on a lesion-per-lesion basis. In this small group of patients, the absence of areas with increased WBC uptake on WBC PET/CT had a 100% negative predictive value. CONCLUSION: Hybrid (18)F-FDG-WBC PET/CT was found to have a high sensitivity and specificity for the diagnosis of infection. It located infectious lesions with a high precision. In this small series, absence of areas with increased uptake virtually ruled out the presence of infection. (18)F-FDG-WBC PET/CT for infection detection deserves further investigation in a larger prospective series.

A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients.

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.

Myocardial homing of nonmobilized peripheral-blood CD34+ cells after intracoronary injection.

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 intra-coronary 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 [18F]-fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment.

Periostitis and hypertrophic osteoarthropathy: etiologies and bone scan patterns in 115 cases.

BACKGROUND: Periostitis, usually seen on X-ray, may be diagnosed on bone scan as non-nodular cortical bone hyperactivity. Both the complete form (including clubbing, arthritis and periostitis) and the incomplete form have been described in association with chronic pulmonary disease, neoplasm, hepatopathy and inflammatory bowel disease. It is not known whether the bone scan pattern of non-nodular cortical bone hyperactivity varies with the etiology. METHODS: We conducted a retrospective study to analyze the etiologies and bone scan patterns of 115 cases of non-nodular cortical bone hyperactivity. RESULTS: Eighty percent of our patients were asymptomatic. Thirty-four percent of all cases of periostitis (all bilateral) were associated with cancer. The rate of cancer in cases of periostitis involving both lower limbs was 28.5%; it was 61.3% when both lower and upper limbs were involved. The duration of the disease was not correlated with either the distribution of periostitis or the intensity of uptake. Moreover, the intensity of uptake was not correlated with the importance of the symptomatology. Bone scan pattern (regular versus heterogenous uptake, localized versus diffuse uptake) was not correlated with the etiology. CONCLUSIONS: Bilateral upper and lower uptake should alert the clinician to the risk of association with neoplasm. Bone scan pattern and intensity of uptake are not necessarily correlated with etiology.

Lung, gastric, and soft tissue uptake of Tc-99m MDP and Ga-67 citrate associated with hypercalcemia.

Metastatic calcifications are associated with chronic renal failure, hyperparathyroidism, metastatic neoplasms, hypervitaminosis D, and hypercalcemia of other origins. Bone scanning agents accumulate within these extraskeletal metastatic calcifications. The authors describe two patients with hypercalcemia associated with Tc-99m MDP uptake in the lungs, stomach, and soft tissues. Ga-67 scintigraphy was also performed and showed increased uptake in the same locations as those of Tc-99m MDP, suggesting the existence of an inflammatory process. Despite adequate treatment, only partial resolution of extraskeletal uptake was observed.

111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content.

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.

Infecton is not specific for bacterial osteo-articular infective pathology.

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.