Intimal angiosarcoma masquerading as retroperitoneal fibrosis.

We present a rare case of intimal angiosarcoma arising from the iliac artery with unusual symptoms and signs mimicking retroperitoneal fibrosis (RPF). This 84-year-old male presented with constitutional symptoms, abdominal pain, increased acute-phase reactant levels, impaired renal function and a CT-documented left-sided parailiac soft-tissue mass with unilateral extrinsic ureteric obstruction. Whole-body 18F-fluorodeoxyglucose positron emission tomography scan showed highly increased FDG-uptake in a horseshoe-like pattern surrounding the left common iliac artery, but no pathologic activity elsewhere. Further diagnostic workup revealed no signs of malignancy. Because of its location, CT-guided biopsy of the mass was precluded. A tentative diagnosis of RPF was made and treatment with Tamoxifen 20 b.i.d. was started. However, his condition gradually deteriorated, eventually succumbing to severe pneumosepsis. Autopsy revealed extensive iliac intimal angiosarcoma with infiltrative expansion to the left ureter and tumor emboli in both lungs. The present case suggests that intimal angiosarcoma should be included in the differential diagnosis of suspected RPF.

18F-FDG micro-PET/CT for intra-operative margin assessment during breast-conserving surgery.

Rationale: Positive surgical margins for invasive breast cancer (BC) treated with breast-conserving surgery (BCS) are defined as ink on tumor. The rate of positive margins is approximately 20%, since a time- and cost-effective method for margin assessment is lacking. In this study, we investigated margin status by intra-operative imaging using high-resolution 18 F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) and X-ray computed tomography (CT).Methods: Twenty patients were enrolled and received 4 MBq/kg of FDG prior to surgery. Intra-operative imaging of the specimens was performed by the MOLECUBES ß-CUBE (PET) and X-CUBE (CT). Margin status was assessed by three surgeons and compared with an algorithm. The sensitivity and specificity were calculated by using histopathological assessment as a gold standard.Results: A region with high FDG uptake was visualized in all specimens. Automated analysis showed a sensitivity of 90%, a specificity of 60%, and an area under the curve (AUC) of 0.86 after ROC analysis. Margin assessment by the surgeons resulted in a mean sensitivity and specificity of 79% and 72%, respectively.Conclusions: This proof-of-concept study demonstrates that high-resolution FDG-PET/CT can facilitate intra-operative margin assessment during BCS. This technique achieves good sensitivity and specificity and may therefore reduce re-operation rates in the future.

Effect of L-arginine on energy metabolism, skeletal muscle and brown adipose tissue in South Asian and Europid prediabetic men: a randomised double-blinded crossover study.

AIMS/HYPOTHESIS: Individuals of South Asian origin are at increased risk of developing type 2 diabetes mellitus and associated comorbidities compared with Europids. Disturbances in energy metabolism may contribute to this increased risk. Skeletal muscle and possibly also brown adipose tissue (BAT) are involved in human energy metabolism and nitric oxide (NO) is suggested to play a pivotal role in regulating mitochondrial biogenesis in both tissues. We aimed to investigate the effects of 6 weeks of supplementation with L-arginine, a precursor of NO, on energy metabolism by BAT and skeletal muscle, as well as glucose metabolism in South Asian men compared with men of European descent. METHODS: We included ten Dutch South Asian men (age 46.5 ± 2.8 years, BMI 30.1 ± 1.1 kg/m2) and ten Dutch men of European descent, that were similar with respect to age and BMI, with prediabetes (fasting plasma glucose level 5.6-6.9 mmol/l or plasma glucose levels 2 h after an OGTT 7.8-11.1 mmol/l). Participants took either L-arginine (9 g/day) or placebo orally for 6 weeks in a randomised double-blind crossover study. Participants were eligible to participate in the study when they were aged between 40 and 55 years, had a BMI between 25 and 35 kg/m2 and did not have type 2 diabetes. Furthermore, ethnicity was defined as having four grandparents of South Asian or white European origin, respectively. Blinding of treatment was done by the pharmacy (Hankintatukku) and an independent researcher from Leiden University Medical Center randomly assigned treatments by providing a coded list. All people involved in the study as well as participants were blinded to group assignment. After each intervention, glucose tolerance was determined by OGTT and basal metabolic rate (BMR) was determined by indirect calorimetry; BAT activity was assessed by cold-induced [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography scanning. In addition, a fasting skeletal muscle biopsy was taken and analysed ex vivo for respiratory capacity using a multisubstrate protocol. The primary study endpoint was the effect of L-arginine on BAT volume and activity. RESULTS: L-Arginine did not affect BMR, [18F]FDG uptake by BAT or skeletal muscle respiration in either ethnicity. During OGTT, L-arginine lowered plasma glucose concentrations (AUC0-2 h - 9%, p < 0.01), insulin excursion (AUC0-2 h - 26%, p < 0.05) and peak insulin concentrations (-26%, p < 0.05) in Europid but not South Asian men. This coincided with enhanced cold-induced glucose oxidation (+44%, p < 0.05) in Europids only. Of note, in skeletal muscle biopsies several respiration states were consistently lower in South Asian men compared with Europid men. CONCLUSIONS/INTERPRETATION: L-Arginine supplementation does not affect BMR, [18F]FDG uptake by BAT, or skeletal muscle mitochondrial respiration in Europid and South Asian overweight and prediabetic men. However, L-arginine improves glucose tolerance in Europids but not in South Asians. Furthermore, South Asian men have lower skeletal muscle oxidative capacity than men of European descent. FUNDING: This study was funded by the EU FP7 project DIABAT, the Netherlands Organization for Scientific Research, the Dutch Diabetes Research Foundation and the Dutch Heart Foundation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02291458.

The diagnostic accuracy of imaging modalities to detect pseudarthrosis after spinal fusion-a systematic review and meta-analysis of the literature.

OBJECTIVE: The aim of the study was to determine the diagnostic accuracy of imaging modalities to detect pseudarthrosis after thoracolumbar spinal fusion, with surgical exploration as reference standard. MATERIALS AND METHODS: A systematic literature search for original studies was performed on the diagnostic accuracy of imaging as index test compared to surgical exploration as reference standard to diagnose pseudarthrosis after thoracolumbar spinal fusion. Diagnostic accuracy values were extracted and methodologic quality of studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Per modality, clinically comparable studies were included in subgroup meta-analysis and weighted odds ratios (ORs) were calculated using the random effects model. RESULTS: Fifteen studies were included. Risk of bias was classified as high/unclear in 58% of the studies. Concerns of applicability was classified as high/unclear in 40% of the studies. Four scintigraphy studies including 93 patients in total were pooled to OR = 2.91 (95% confidence interval [CI]: 0.93-9.13). Five studies on plain radiography with 398 patients in total were pooled into OR = 7.07 (95% CI: 2.97-16.86). Two studies evaluating flexion-extension radiography of 75 patients in total were pooled into OR = 4.00 (95% CI: 0.15-105.96). Two studies of 68 patients in total were pooled for CT and yielded OR = 17.02 (95% CI: 6.42-45.10). A single study reporting on polytomography, OR = 10.15 (95% CI 5.49-18.78), was also considered to be an accurate study. CONCLUSIONS: With a pooled OR of 17.02, CT can be considered the most accurate imaging modality for the detection of pseudarthrosis after thoracolumbar spinal fusion from this review.

Regional alterations of cerebral [18F]FDG metabolism in the chronic unpredictable mild stress- and the repeated corticosterone depression model in rats.

Preclinical research has been indispensable in the exploration of the neurological basis of major depressive disorder (MDD). The present study aimed to examine effects on regional brain activity of two frequently used depression models, the chronic unpredictable mild stress (CUMS)- and the chronic corticosterone (CORT) depression model. The CUMS and CORT depression model were induced by exposing male Long-Evans rats to a 4-week procedure of unpredictable mild stressors or a 3-week procedure of chronic corticosterone, respectively. Positron emission tomography with [18F]FDG was performed to determine alterations in regional brain activity. In addition, depressive- and anxiety-like behaviour was assessed via the forced swim test and the open field test, respectively. The chronic CORT administration, but not the CUMS model, significantly induced depressive-like behaviour and elevated plasma corticosterone levels. Compared to control, induction of the CORT depression model resulted in a significantly reduced glucose consumption in the insular cortex and the striatum, and a significantly elevated consumption in the cerebellum and the midbrain. Induction of the CUMS model replicated the findings with respect to the activity in the striatum region, and cerebellum, but missed significance in the insular cortex and the midbrain. Based on the alterations in behaviour and regional [18F]FDG uptake, a superior face validity and construct validity can be observed after induction of depression via chronic CORT injections, compared to the used CUMS paradigm.

Added value of 18F-FDG PET/CT in diagnosing infected hip prosthesis.

Background The diagnosis of infected hip prosthesis is frequently not straightforward yet very important as it changes treatment. Purpose To retrospectively investigate the added value of 18F-FDG PET/CT to conventional tests including radiography, erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) testing, and joint aspiration, in diagnosing infected hip prosthesis. Material and Methods Seventy-eight hip prostheses of 78 patients (55% men; mean age = 66.5 years; age range = 30-85 years) with non-specific clinical presentation, i.e. no abscess or sinus tract communicating with the joint space at clinical examination, were analyzed. Cultures of intra-articular fluid and peri-implant tissues after revision surgery or clinical follow-up ≥6 months served as gold standard. Areas under the receiver operating characteristic curves (AUCs) of radiography, ESR/CRP testing, aspiration culture, and white blood cell (WBC) count without and with the addition of 18F-FDG PET/CT were compared. Results The addition of 18F-FDG PET/CT increased AUCs: for radiography with 0.212, P = 0.001; for ESR/CRP testing with 0.076, P = 0.072; for aspiration culture with 0.126, P = 0.032; and for aspiration WBC count with 0.191, P = 0.035. Conclusion This study shows that 18F-FDG PET/CT adds to individual conventional tests in diagnosing infected hip prosthesis. It may improve the preoperative planning and should therefore be considered in the diagnostic work-up. Future studies should define the exact place of 18F-FDG PET/CT in the diagnostic work-up of periprosthetic joint infection.

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance.

AIMS/HYPOTHESIS: Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation­at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. METHODS: We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) imaging. RESULTS: We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. CONCLUSIONS/INTERPRETATION: Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. TRIAL REGISTRATION: www.trialregister.nl NTR3523 FUNDING: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

Diagnostic Performance of Dedicated Axillary T2- and Diffusion-weighted MR Imaging for Nodal Staging in Breast Cancer.

PURPOSE: To evaluate the diagnostic performance of unenhanced axillary T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) imaging for axillary nodal staging in patients with newly diagnosed breast cancer, with node-by-node and patient-by-patient validation. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Fifty women (mean age, 60 years; range, 22-80 years) underwent high-spatial-resolution axillary 3.0-T T2-weighted imaging without fat suppression and DW imaging (b = 0, 500, and 800 sec/mm(2)), followed by either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection. Two radiologists independently scored each lymph node on a confidence level scale from 0 (benign) to 4 (malignant), first on T2-weighted MR images, then on DW MR images. Two researchers independently measured the mean apparent diffusion coefficient (ADC) of each lymph node. Diagnostic performance parameters were calculated on the basis of node-by-node and patient-by-patient validation. RESULTS: With respective node-by-node and patient-by-patient validation, T2-weighted MR imaging had a specificity of 93%-97% and 87%-95%, sensitivity of 32%-55% and 50%-67%, negative predictive value (NPV) of 88%-91% and 86%-89%, positive predictive value (PPV) of 60%-70% and 62%-75%, and area under the receiver operating characteristic curve (AUC) of 0.78 and 0.80-0.88, with good interobserver agreement (κ = 0.70). The addition of DW MR imaging resulted in lower specificity (59%-88% and 50%-84%), higher sensitivity (45%-64% and 75%-83%), comparable NPV (89% and 90%-91%), lower PPV (23%-42% and 34%-60%), and lower AUC (0.68-0.73 and 0.70-0.86). ADC measurement resulted in a specificity of 63%-64% and 61%-63%, sensitivity of 41% and 67%, NPV of 85% and 85%-86%, PPV of 18% and 35%-36%, and AUC of 0.54-0.58 and 0.69-0.74, respectively, with excellent interobserver agreement (intraclass correlation coefficient, 0.83). CONCLUSION: Dedicated high-spatial-resolution axillary T2-weighted MR imaging showed good specificity on the basis of node-by-node and patient-by-patient validation, with good interobserver agreement. However, its NPV is still insufficient to substitute it for SLNB for exclusion of axillary lymph node metastasis. DW MR imaging and ADC measurement were of no added value.

Three-Dimensional Breast Radiotherapy and the Elective Radiation Dose at the Sentinel Lymph Node Site in Breast Cancer.

BACKGROUND: Several trials are presently randomizing clinically node-negative breast cancer patients treated with breast-conserving therapy (BCT) to sentinel lymph node biopsy (SLNB) or watchful waiting. We aimed to investigate the elective radiation dose at the sentinel lymph node (SLN) site while evaluating two techniques for SLN localization, in breast cancer patients treated with lumpectomy and three-dimensional (3D) whole-breast radiotherapy. METHODS: The SLN site of consecutive Tis-2N0 breast cancer patients undergoing lumpectomy and forward intensity-modulated whole-breast radiotherapy was determined by the location of the hotspot on preoperative single-photon emission computed tomography (SPECT)/computed tomography (CT) and by a surgical clip placed at the removed SLN(s) during SLNB. The radiation dose at the SLN site was subsequently determined on the postoperative radiotherapy planning CT. An elective radiation dose to the SLN site was defined as at least 95 % of the breast dose. RESULTS: Of the 42 included patients, the mean percentage of the breast dose on the SLN site was 90 % (standard deviation 26, range 7-132, median 99), with a non-significant difference between the two techniques (surgical clip or SPECT/CT) (p = 0.608). In 32/42 patients (76 %) the SLN site received an elective radiation dose. CONCLUSIONS: A surgical clip placed at the removed SLN(s) during SLNB proved to be an adequate method of determining the radiation dose at the SLN site when compared with using SPECT/CT. With the use of 3D radiotherapy, the site of the SLN is treated with an elective radiation dose in the majority of patients who are treated with BCT.

Pseudarthrosis after lumbar spinal fusion: the role of ¹8F-fluoride PET/CT.

PURPOSE: Painful pseudarthrosis is one of the most important indications for (revision) surgery after spinal fusion procedures. If pseudarthrosis is the source of recurrent pain it may require revision surgery. It is therefore of great clinical importance to ascertain if it is the source of such pain. The correlation between findings on conventional imaging (plain radiography and CT) and clinical well-being has been shown to be moderate. The goal of this study was to determine the possible role of (18)F-fluoride PET in patients after lumbar spinal interbody fusion by investigating the relationship between PET/CT findings and clinical function and pain. METHODS: A cohort of 36 patients was retrospectively included in the study after (18)F-fluoride PET/CT for either persistent or recurrent low back pain (18 patients) or during routine postoperative investigation (18 patients) between 9 and 76 months and 11 and 14 months after posterior lumbar interbody fusion, respectively. Sixty minutes after intravenous injection of 156 - 263 MBq (mean 199 MBq, median 196 MBq) (18)F-fluoride, PET and CT images were acquired using an integrated PET/CT scanner, followed by a diagnostic CT scan. Two observers independently scored the images. The number of bony bridges between vertebrae was scored on the CT images to quantify interbody fusion (0, 1 or 2). Vertebral endplate and intervertebral disc space uptake were evaluated visually as well as semiquantitatively following (18)F-fluoride PET. Findings on PET and CT were correlated with clinical wellbeing as measured by validated questionnaires concerning general daily functioning (Oswestry Disability Index), pain (visual analogue scale) and general health status (EuroQol). Patients were divided into three categories based on these questionnaire scores. RESULTS: No correlation was found between symptom severity and fusion status. However, (18)F-fluoride activity in the vertebral endplates was significantly higher in patients in the lowest Oswestry Disability Index category (i.e. with the worst clinical performance) than in patients in higher categories (p = 0.01 between categories 1 and 2 and 1 and 3). The visual analogue scale and EuroQol results were similar although less pronounced, with only SUVmax between category 1 and 2 being significantly different (p = 0.04). CONCLUSION: We hypothesize that (18)F-fluoride PET/CT may be able to provide support for the diagnosis of painful pseudarthrosis and could serve as a tool to discriminate between symptomatic and asymptomatic pseudarthrosis for revision surgery, as CT defines the consolidation status and PET pinpoints the 'stress reaction' at the vertebral endplates which significantly correlates with Oswestry Disability Index score.

Protein kinase-D1 overexpression prevents lipid-induced cardiac insulin resistance.

In the insulin resistant heart, energy fuel selection shifts away from glucose utilization towards almost complete dependence on long-chain fatty acids (LCFA). This shift results in excessive cardiac lipid accumulation and eventually heart failure. Lipid-induced cardiomyopathy may be averted by strategies that increase glucose uptake without elevating LCFA uptake. Protein kinase-D1 (PKD1) is involved in contraction-induced glucose, but not LCFA, uptake allowing to hypothesize that this kinase is an attractive target to treat lipid-induced cardiomyopathy. For this, cardiospecific constitutively active PKD1 overexpression (caPKD1)-mice were subjected to an insulin resistance-inducing high fat-diet for 20-weeks. Substrate utilization was assessed by microPET and cardiac function by echocardiography. Cardiomyocytes were isolated for measurement of substrate uptake, lipid accumulation and insulin sensitivity. Wild-type mice on a high fat-diet displayed increased basal myocellular LCFA uptake, increased lipid deposition, greatly impaired insulin signaling, and loss of insulin-stimulated glucose and LCFA uptake, which was associated with concentric hypertrophic remodeling. The caPKD1 mice on high-fat diet showed none of these characteristics, whereas on low-fat diet a shift towards cardiac glucose utilization in combination with hypertrophy and ventricular dilation was observed. In conclusion, these data suggest that PKD pathway activation may be an attractive therapeutic strategy to mitigate lipid accumulation, insulin resistance and maladaptive remodeling in the lipid-overloaded heart, but this requires further investigation.

Cold-activated brown adipose tissue in human adults: methodological issues.

The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e., close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) imaging. Dynamic imaging provides quantitative information about glucose uptake rates, whereas static imaging reflects overall BAT glucose uptake, localization, and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET image, leading to spillover. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [18F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the "fixed volume" methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like magnetic resonance imaging or thermography, is discussed.

Molecular imaging of brown adipose tissue in health and disease.

PURPOSE: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. METHODS: This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. RESULTS: Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, (18)F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to (18)F-FDG, other radiopharmaceuticals such as (99m)Tc-sestamibi, (123)I-metaiodobenzylguanidine (MIBG), (18)F-fluorodopa and (18)F-14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. CONCLUSION: Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.

Comparison of [18 F]FDG PET/CT and MRI in the diagnosis of active osteomyelitis.

OBJECTIVE: In diagnosing osteomyelitis (OM) both MRI and [18 F]FDG PET-CT proved to be accurate modalities. In anticipation of the advent of hybrid PET/MRI scanners we analyzed our patient group to give direction to future imaging strategies in patients with suspected OM. MATERIALS AND METHODS: In this retrospective study all patients of a tertiary referral center who underwent both an MRI and a PET for the diagnosis of OM were included. The results of those scans were evaluated using patient's histology, microbiological findings, and clinical/radiological follow-up. Additionally, ROC curve analysis of the SUVmax and the SUVmax ratio on the PET scans was performed. Two imaging strategies were simulated: first MRI followed by PET, or vice versa. RESULTS: Twenty-seven localizations in 26 patients were included. Both MRI and PET were shown to be accurate in our patients for the qualitative detection of OM. A cut-off value for the SUVmax of 3 gave optimal results (a specificity of 90 % with a sensitivity of 88 %). The SUVmax ratio gave a worse performance. The two simulated imaging strategies showed no difference in the final diagnosis in 20 out of 27 cases. Remarkably, 6 equivocal cases were all correctly diagnosed by the second modality, i.e., PET or MRI. CONCLUSION: Both MRI and [18 F]FDG PET were accurate in diagnosing OM in a tertiary referral hospital population. Simulation of imaging strategies showed that a combined sequential strategy was optimal. It seems preferable to use MRI as a primary imaging tool for uncomplicated unifocal cases, whereas in cases with (possible) multifocal disease or a contraindication for MRI, PET is preferred. This combined sequential strategy looks promising, but needs to be confirmed in a larger prospective study.

(18)F-FDG microPET imaging differentiates between septic and aseptic wound healing after orthopedic implant placement: a longitudinal study of an implant osteomyelitis in the rabbit tibia.

BACKGROUND AND PURPOSE: (18)F-FDG PET is a widely used tool for molecular imaging of oncological, cardiovascular, and neurological disorders. We evaluated (18)F-FDG microPET as an implant osteomyelitis imaging tool using a Staphylococcus aureus-induced peroperative implant infection in rabbits. METHODS: Intramedullary titanium nails were implanted in contaminated and uncontaminated (control) proximal right tibiae of rabbits. Tibiae were quantitatively assessed with microPET for (18)F-FDG uptake before and sequentially at 1, 3, and 6 weeks after surgery. Tracer uptake was assessed in soft tissue and bone in both treatment groups with an additional comparison between the operated and unoperated limb. MicroPET analysis was combined with radiographic assessment and complementary histology of the tibiae. RESULTS: At the first postoperative week, the (18)F-FDG uptake in the contaminated implant group was significantly higher than the preoperative measurement, without a significant difference between the contaminated and uncontaminated tibiae. From the third postoperative week onward, (18)F-FDG uptake allowed discrimination between osteomyelitis and postoperative aseptic bone healing, as well as quantification of the infection at distinct locations around the implant. INTERPRETATION: (18)F-FDG-based microPET imaging allows differentiation between deep infection and undisturbed wound healing after implantation of a titanium intramedullary nail in this rabbit model. Furthermore, our results indicate that (18)F-FDG PET may provide a tool in human clinical diagnostics and for the evaluation of antimicrobial strategies in animal models of orthopedic implant infection.

The Use of 18F-Fluoride Positron Emission Tomography/Computed Tomography Scanning to Identify Sources of Pain after Posterior Lumbar Interbody Fusion-An Analysis in Patients with and without Symptoms.

BACKGROUND: Identifying the cause of recurrent or persisting pain after posterior lumbar interbody fusion (PLIF) is essential for establishing optimal treatment. In this study, we evaluate patients after PLIF surgery by 18F-fluoride PET/CT scans and patient-reported outcome measures (PROMs). METHODS: A total of 36 PLIF patients were included. Sixty minutes after intravenous injection of 18F-fluoride, PET/CT scanning was performed. Bone graft ingrowth, subsidence, screw loosening and damage of facet joints were scored by quantifying the level of bone metabolism of the vertebral endplates in the disc spaces, around screws and around the facet joints on the PET scans. RESULTS: In contrast to asymptomatic patients, symptomatic patients showed abnormal PET values around pedicle screws and/or facet joints and at the lower endplates of the disc spaces, identifying a possible source of pain. On CT, no significant differences between these two groups were found. CONCLUSION: The PET/CT findings appeared to correlate better with symptoms on PROMs compared to CT findings alone. When interpreting 18F-fluoride PET/CT findings after PLIF surgery, one should realize bone metabolism in the disc spaces of the operated segments and around pedicle screws or facet joint changes during follow-up, reflecting natural recovery.

¹²4I PET/CT in the pretherapeutic staging of differentiated thyroid carcinoma: comparison with posttherapy ¹³¹I SPECT/CT.

PURPOSE: To compare pretherapy (124)I PET/CT and posttherapy (131)I SPECT/CT in the identification of pathological lesions and the staging of patients with differentiated thyroid carcinoma. METHODS: (124)I SPECT with low-dose CT in addition to a standard whole-body scan was performed 5 days following (131)I therapy with the administration of 1,110-7,728 MBq. Pretherapy (124)I PET/CT was done 24 h and 96 h after oral ingestion of 20-28 MBq, including a noncontrast high-dose CT scan. Scans were evaluated by two independent experienced nuclear physicians. In addition to the total number of lesions found, patient-based analyses and lesion-based analyses were performed to ascertain the discrepancies between the findings of the two scanning techniques, as well as to evaluate the clinical impact of the findings. RESULTS: A group of 20 consecutive patients were analysed. In the lesion-based analysis, a total of 62 foci were found with all modalities together. Of these, (124)I PET/CT found 57 (92 %), (131)I SPECT/CT 50 (81 %) and planar imaging 39 (63 %). In the patient-based analysis, in 50 % of patients complete concordance between the findings of (124)I PET and (131)I SPECT was seen, in 5 % complete discordance and in the remaining 45 % partial discordance, i.e. a focus or some foci seen with both modalities but another or others seen more or less with one or other modality. In 5 of the 20 patients (25 %), tumour stage was changed according to the findings of one of the modalities. In 60 % of these patients this was only with the findings of (124)I PET/CT. CONCLUSION: This study showed that (124)I PET/CT is preferred over (131)I imaging for staging differentiated thyroid carcinoma.

Molecular nuclear therapies for thyroid carcinoma.

Thyroid cancer, divided in the subvarieties of papillary and follicular carcinoma, together also called differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC), is the most common endocrine malignancy. Over the course of the last seven decades multiple molecular nuclear therapies have been tried to treat the various varieties of thyroid cancer. The sodium iodine symporter (NIS) substrate I-131 is a well known and extremely successful agent to treat DTC, but is not successful in treating other thyroid cancer varieties and some de-differentiated DTC tumors. An alternative to I-131 are radioactively labeled somatostatin analogues, which have predominantly been used to target MTC, but may also be effective in some DTC cases. In experimental preclinical studies the re-induction of NIS expression or transfection with recombinant NIS shows some promise for the treatment of ATC and dedifferentiated DTC. Furthermore, several other potential radioactive NIS substrates are developed. In this review, we will extensively discuss the aforementioned established therapeutic modalities and promising new concepts in molecular nuclear therapy of thyroid carcinoma.

Dosimetry in molecular nuclear therapy.

Advanced personalized dosimetry for molecular nuclear therapy has been shown to be feasible in clinical practice. At the same time instrumentation and dosimetric software are still evolving at a high pace. Procedures developed so far differ in approach and sophistication, and standard operating procedures necessary for accurate patient specific dosimetry do not yet exist. For this reason we restricted ourselves to reviewing the literature and highlighting relevant developments.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10-20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918-928, 1985); Schafer and Sorrell (Lancet 353:1253-1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for (131)I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901-906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical (131)I-Lipiodol (Lipiocis®, IBA, Brussels, Belgium) and include the newer medical devices with (90)Y-microspheres. (90)Y is either bound to resin (SIR-Spheres®, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere®, MDS Nordion, Kanata, ON, Canada). Since (90)Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.