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Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with90Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2–50.6). Outcomes were: complete response (n=2), partial response (n=13), stable disease (n=1), and progressive disease (n=2) giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare90Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.

Contralateral hypertrophy after 90Y radioembolization has been described in case reports, but the incidence and quantitative extent of liver volume modifications after this therapy are unknown. This retrospective study examined patients with hepatocellular carcinoma and underlying cirrhosis treated by 90Y radioembolization. The main inclusion criteria were unilateral treatment, no prior liver surgery, and computed tomographic scans allowing for volumetric assessments. Treated, tumor, and contralateral liver volumes were measured. Whole liver volume and the ratio of contralateral to total functional liver volume after a virtual hepatectomy were calculated. Data of 34 patients were analyzed. Response rates were 26 % according to Response Evaluation Criteria in Solid Tumors (RECIST) and 63 % according to modified RECIST. Median overall survival was 13.5 months. Median treated volume decreased from 938 mL (interquartile range [IQR] = 719) to 702 mL (IQR = 656) (p

International audience; The aim of this study was to develop new Lipiodol formulations with increased viscosities to augment Lipiodol embolic effect and optimize efficiency of radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations consist of Lipiodol mixtures with different stearic acid concentrations (0.8%, 1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity, rheologic profiles) and labeled with 99mTc. Their viscosities at 20°C are 54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second, their biodistribution profiles were studied in vivo, at 24 and 72 hours, in hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol). Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum obtained with 1.3% stearic acid, and a tumor uptake superior to control group (+67%) (p

International audience; Rhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic.

International audience; The goal of this study was to assess the use of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) analysis for vascularized volume measurements in the use of the yttrium-90-radiolabeled microspheres (TheraSphere). A phantom study was conducted for the validation of SPECT/CT volume measurement. SPECT/CT quantitative analysis was used for the measurement of the volume of distribution of the albumin macroaggregates (MAA; i.e., the vascularized volume) in the liver and the tumor, and the total activity contained in the liver and the tumor in four consecutive patients presenting with a complex liver vascularization referred for a treatment with TheraSphere. SPECT/CT volume measurement proved to be accurate (mean error

Purpose The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) in assessing response at the end of induction therapy is well documented in Hodgkin's and diffuse large B-cell lymphomas, but its role in follicular lymphoma (FL) remains undetermined. We investigated the prognostic significance of PET-CT performed after first-line therapy in patients with FL treated in the prospective Primary Rituximab and Maintenance (PRIMA) study. Patients and Methods Results of PET-CT scans performed after induction immunochemotherapy were recorded retrospectively. Patients went on to either observation or rituximab maintenance per protocol independent of the PET-CT result. Patient characteristics and outcomes were then evaluated. Results Of 122 PET-CT scans performed at the end of the induction immunochemotherapy, 32 (26%) were reported as positive by the local investigator. Initial demographic or disease characteristics did not differ between PET-CT–positive (PET-positive) and PET-CT–negative (PET-negative) patients. PET status correlated with conventional response criteria (P < .001). Patients remaining PET positive had a significantly (P < .001) inferior progression-free survival at 42 months of 32.9% (95% CI, 17.2% to 49.5%) compared with 70.7% (95% CI, 59.3% to 79.4%) in those who became PET negative. PET status, but not conventional response (complete response or complete response unconfirmed v partial response) according to IWC 1999, was an independent predictive factor for lymphoma progression. The risk of death was also increased in PET-positive patients (hazard ratio 7.0; P = .0011). Conclusion [18F]FDG PET-CT status at the end of immunochemotherapy induction in patients with FL is strongly predictive of outcome and should be considered a meaningful clinical end point in future studies.

International audience; BACKGROUND: The drug (131)I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration. METHODS: Cases were retrospectively identified through the drug safety unit database of Rennes University Hospital. RESULTS: From 1994 to 2009, interstitial pneumonia developed in 15 patients following (131)I-labeled lipiodol administration, with an estimated prevalence of 15.5 cases (95% CI, 7.7-23.2) per 1,000 treated patients. Mean age of the patients was 60 ± 8 years, and the male to female ratio was 6.5:1. All patients had cirrhosis, mainly related to long-term alcohol intoxication (n = 12). Most (n = 10) cases occurred after the second (131)I-labeled lipiodol injection. The median delay between last (131)I-labeled lipiodol administration and first respiratory symptoms was 30 days (interquartile range, 16.5-45 days). All patients presented with shortness of breath. Physical examination mostly revealed fever (n = 11) and bilateral crackles (n = 12). Chest CT scan showed bilateral ground-glass opacities (n = 8) with septal thickening, retraction, or both (n = 8). BAL (n = 7) was remarkable for increased neutrophils (n = 4) or CD8(+) T cell count (n = 3). Despite corticosteroids, 12 (80%) patients died, mostly of untractable respiratory failure (n = 9). Median delay between last (131)I-labeled lipiodol injection and death was 63 days (interquartile range, 34-129 days). CONCLUSIONS: Interstitial pneumonia may be a serious and not uncommon complication of (131)I-labeled lipiodol administration.

International audience; This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52±2.3% and extraction yield was 98.56±1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68±9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ((188)Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07±0.9%).

Objectives. The aim of this study was to assess the effectiveness of SPECT/CT for volume measurements and to report a case illustrating the major impact of SPECT/CT in calculating the vascularized liver volume and dosimetry prior to injecting radiolabelled yttrium-90 microspheres (Therasphere). Materials and Methods. This was a phantom study, involving volume measurements carried out by two operators using SPECT and SPECT/CT images. The percentage of error for each method was calculated, and interobserver reproducibility was evaluated. A treatment using Therasphere was planned in a patient with three hepatic arteries, and the quantitative analysis of SPECT/CT for this patient is provided. Results. SPECT/CT volume measurements proved to be accurate (mean error 3) and reproductive (interobserver agreement = 0.9). In the case report, 99mTc-MAA SPECT/CT identified a large liver volume, not previously identified with angiography, which was shown to be vascularized after selective MAA injection into an arterial branch, resulting in a large modification in the activity of Therasphere used. Conclusions. MAA SPECT/CT is accurate for vascularized liver volume measurements, providing a valuable contribution to the therapeutic planning of patients with complex hepatic vascularization.

International audience; Objectives. The aim of this study was to assess the effectiveness of SPECT/CT for volume measurements and to report a case illustrating the major impact of SPECT/CT in calculating the vascularized liver volume and dosimetry prior to injecting radiolabelled yttrium-90 microspheres (Therasphere). Materials and Methods. This was a phantom study, involving volume measurements carried out by two operators using SPECT and SPECT/CT images. The percentage of error for each method was calculated, and interobserver reproducibility was evaluated. A treatment using Therasphere was planned in a patient with three hepatic arteries, and the quantitative analysis of SPECT/CT for this patient is provided. Results. SPECT/CT volume measurements proved to be accurate (mean error

TO THE EDITOR: We read with great interest the paper by Ulrich et al. ([1][1]) reporting on the predictive value of 99mTc-macroaggregated albumin (99mTc-MAA) uptake in patients with colorectal liver metastasis scheduled for selective internal radiation therapy (SIRT) with 90Y-loaded resin

International audience; PURPOSE: The aim of this study was to assess the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma. METHODS: A retrospective study was performed on 45 patients with untreated biopsy-proven follicular lymphoma who underwent 18F-fluorodeoxyglucose PET/CT (FDG PET/CT) and CT before and after chemoimmunotherapy induction treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone). RESULTS: PET/CT detected more nodal (+51%) and extranodal (+89%) lesions than CT. PET/CT modified Ann Arbor staging in eight patients (18%). Five patients (11%) initially considered as being early stage (I/II) were eventually treated as advanced stage (III/IV). In this study, an initial PET/CT prognostic score was significantly more accurate than the Follicular Lymphoma International Prognostic Index score in identifying patients with poor prognosis (i.e. patients with incomplete therapeutic response or early relapse). The accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses. In addition, post-treatment PET/CT was able to predict patients' outcomes. The median progression-free survival was 48 months in the PET/CT-negative group as compared with 17.2 months for the group with residual uptake (p

International audience; Background:High-frequency bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is a promising treatment in refractory obsessive-compulsive disorder (OCD). Method Using the crossover, randomized, and double-blind procedure adopted by the STOC study, 10 patients treated with high-frequency bilateral STN DBS underwent am 18-fluorodeoxyglucose positron emission tomography (PET) investigation to highlight the neural substratum of this therapeutic approach. Results The median YaleBrown Obsessive Compulsive Scale (Y-BOCS) scores for all 10 patients were 31 (minimum = 18, maximum = 36) with "Off-Stimulation" status and 19 (minimum = 0, maximum = 30) with "On-Stimulation" status (p = .05). The OCD patients in Off-Stimulation status showed a hypermetabolism in the right frontal middle and superior gyri, right parietal lobe, postcentral gyrus, and bilateral putamen compared with healthy control subjects. A significant decrease in cerebral metabolism was observed in the left cingulate gyrus and the left frontal medial gyrus in On-Stimulation conditions compared with Off-Stimulation conditions. In addition, the improvement assessed by Y-BOCS scores during the On-Stimulation conditions was positively correlated with PET signal changes at the boundary of the orbitofrontal cortex and the medial prefrontal cortex, between PET signal changes and the Y-BOCS scores modifications in On-Stimulation status. Conclusion This study suggests that the therapeutic effect of STN DBS is related to a decrease in prefrontal cortex metabolism. © 2010 Society of Biological Psychiatry.

International audience; INTRODUCTION: Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy. METHODS: The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of (99m)Tc-SSS-Lipiodol. RESULTS: The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 μM for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of (99m)Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57 ± 3.65% after treatment, as against 9.45 ± 4.44% without treatment (P

International audience; Hepatocellular carcinoma (HCC) is becoming an important public health concern. Current therapeutic options are limited and new treatments are therefore being developed. The intra-arterial treatment chemoembolization has limited efficacy and few prospects for further progress. One particularly promising, though little used, alternative to chemoembolization is radioembolization with iodine-131 ((131)I) or rhenium-188 labeled lipiodol or yttrium-90 labeled microspheres (glass or resin beads). Three randomized studies have proven the effectiveness of (131)I-lipiodol in patients with HCC-as adjuvant therapy after surgery, compared with chemoembolization, and also in patients who have portal vein thrombosis. Microspheres enable the delivery of high-dose radiation (>200 Gy) to the tumor while sparing the neighboring hepatic tissue from overexposure. Overall, the efficacy of radioembolization has been good and toxic effects have been low. These results are comparable to those obtained with chemoembolization but further improvement can be expected by combining radioembolization with standard chemotherapy or with targeted therapies, such as anti-angiogenic drugs.

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International audience; PURPOSE: Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. METHODS: We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using (18)F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. RESULTS: The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. CONCLUSION: These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role.

The treatment of metastatic neuroendocrine tumors depends on the aggressiveness of the disease. We wanted to know whether (18)F-FDG PET and somatostatin receptor scintigraphy (SRS) can predict early disease progression and patient survival.We undertook a prospective study of patients with metastatic neuroendocrine tumor diagnosed between September 2003 and January 2006. After obtaining signed informed consent from the patients, we performed CT, SRS, and (18)F-FDG PET and reviewed histologic data. CT was repeated every 3 mo to assess the risk of early progressive disease (first 6 mo), progression-free survival, and overall survival.Thirty-eight patients (mean age, 60 +/- 15 y) were included. Histologically, 4 patients had a high-grade and 34 a low-grade tumor. The results of (18)F-FDG PET and SRS were positive in 15 and 27 patients. The 2-y overall survival and progression-free survival were 73% and 45%; 16 patients had early progressive disease. Most (18)F-FDG PET-positive patients had early progressive disease (14/15, vs. 2/23 (18)F-FDG PET-negative patients), and most SRS-negative patients had early progressive disease (9/11, vs. 7/27 SRS-positive patients); (18)F-FDG PET gave excellent negative and positive predictive values of 91% and 93%; (18)F-FDG PET results correlated with progression-free survival (P0.001) and overall survival (P0.001) even when only low-grade tumors were considered. SRS was associated with progression-free survival (P0.001) and overall survival (P0.03). At multivariate analysis, only (18)F-FDG PET was predictive of progression-free survival.(18)F-FDG PET exhibits excellent predictive values for early tumor progression. (18)F-FDG PET and SRS results correlate with progression-free survival and overall survival even for histologically low-grade tumors. These explorations could be included in the initial work-up for metastatic neuroendocrine tumor.

International audience; Objective: Apathy may be induced by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease (PD). We therefore wished to test the hypothesis that apathy induced by STN-DBS correlates with changes in glucose metabolism, using (18)FDG-PET. Methods: Twelve patients with PD were assessed 3 months before (M - 3) and 3 months after (M = 3) STN-DBS with (18)FDG-PET and the Apathy Evaluation Scale. Results: Apathy had significantly worsened at M = 3 after STN-DBS. Positive correlations were observed between this variation in apathy scores and changes in glucose metabolism, especially in the right frontal middle gyrus (Brodmann area [BA] 10) and right inferior frontal gyrus (BA 46 and BA 47). Negative correlations between the two were observed in the right posterior cingulate gyrus (BA 31) and left medial frontal lobe (BA 9). Conclusion: These preliminary results confirm the role of the subthalamic nucleus in associative and limbic circuitry in humans and suggest that it is a key basal ganglia structure in motivation circuitry. Neurology (R) 2009; 73: 1746-1751

Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide; in fact, it is ranked fifth in importance with approximately 437,000 new cases per annum (Bosch et al. 1999). Its incidence is increasing in many countries (Trinchet and Beaugrand 1999; Taylor-Robinson et al. 1997; Deuffic and Poynard 1998; El-Serag and Mason 1999). The first recognized risk factor is the presence of a cirrhosis that may be associated with various possible aetiologies (B and C viral infections, alcohol, haemochromatosis). This increased incidence is related to the better health care of patients suffering from cirrhosis, but also to a strong increase in chronic hepatitis C (Trinchet and Beaugrand 1999; Taylor-Robinson et al. 1997; Deuffic and Poynard 1998; Okuda 2000). Indeed, in France, approximately 500,000 people would appear to be infected by the hepatitis C virus (Trinchet and Beaugrand 1999). It is estimated that about 66 % present with chronic hepatitis and that 20 % will develop cirrhosis in 10–20 years in the absence of treatment. In France, it is estimated that the mortality linked to HCC occurring with hepatitis C virus cirrhosis will increase by 150% in men and 200% in women from now until 2020 (Deuffic et al. 1999). We may thus consider that, in the years to come, HCC will pose a problem for public health.

International audience; Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinsons disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinsons disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using (18)FDG-PET. The (18)FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits.

International audience; This bicentric study assessed retrospectively the usefulness of 18 F-FDG-PET in the staging of 31 patients with lymphocyte-predominant Hodgkin's disease (LPHD). FDG-PET and conventional explorations (CE) were performed for initial disease (n=25) or recurrence (n= 6). All the 68 involved sites were detected by PET including 5 extra-nodal lesions. Only 43 nodal sites (68%) and one splenic focus were detected by CE. PET changed staging in 9 patients (7 upstaged, 2 downstaged) and radiation fields in 3 patients. These results showed the potential role of PET in the staging of LPHD.

For radionuclide therapy of hepatocellular carcinoma, there have been many attempts to label Lipiodol (an iodinated ester of popyseed oil) with therapeutic radioisotopes, including 131I, 90Y, 186Re and 188Re. 131I-labelled Lipiodol is a commercially available radiopharmaceutical that is currently used in many countries. Nonetheless, despite encouraging results, there are some disadvantages with Iodine- 131, in particular the low-energy beta and high-energy gamma emissions as well as its long half-life. Rhenium-188 is an attractive alternative, since it has a higher beta energy coupled with a shorter physical half-life. In addition, 188Re emits a 155 keV γ-ray with an abundance of 15 % suitable for monitoring biodistribution and calculating dosimetry. A further advantage is that 188Re is now conveniently produced via a 188W/188Re generator system, enabling the on-site production of 188Re-radiopharmaceuticals. Over the last few years, efforts to label Lipiodol with 188Re have led to a very active area of research. Two strategies have been studied, namely i) covalent bonding between Lipiodol and the 188Re-chelate, and ii) solubilisation of a lipophilic 188Re-complex into cold Lipiodol. While some of these approaches are currently under clinical investigation, one of them is being sponsored by the International Atomic Energy Agency. The preliminary results indicate the feasibility of using rhenium-188, which shows good tolerance and good response rates in the treatment of unresectable HCC as well as in adjuvant or neo-adjuvant settings.

We carried out a study to evaluate the contribution of positron emission tomography with (18)F-fluorodeoxyglucose (PET-FDG) in the diagnosis and therapeutic care of patients presenting with metastases of unknown primary. PET-FDG was prospectively performed in 51 patients. The PET-FDG data were confirmed histologically or by a follow-up on average at 13 months. PET-FDG identified the primary in 24 percent of cases, and detected the presence of additional metastases in 41 percent of cases. PET-FDG led to a therapeutic modification for 12 patients (24 percent). Furthermore, the therapeutic impact seems more marked in localized forms than in the multifocal. This broad exploratory study confirms the important role of PET-FDG in the diagnosis and therapeutic management of patients with metastases of unknown primary.

REPLY: We have read with great interest the comments of Hofman et al. regarding our recently published study ([1][1]) about the high prognostic value of 18F-FDG PET for metastatic neuroendocrine tumors (NETs). In that prospective study, patients with 18F-FDG–avid NETs, defined by a standardized

This study focuses on a promising carrier system for imaging and therapeutic purposes using lipid nanocapsules. To assess their potential for clinical use, we labelled nanocapsules with (99m)Tc and (188)Re and analysed some kinetic biodistribution parameters after intravenous injection in rats.Lipophilic complexes [(99m)Tc/(188)Re(S(3)CPh)(2)(S(2)CPh)] ((99m)Tc/(188)Re-SSS) were encapsulated within the nanoparticles during their manufacture with quantitative yield and satisfactory radiochemical purity. Rats were injected intravenously with 3.7 MBq (99m)Tc/(188)Re-labelled nanocapsules and sacrificed at 5, 15 and 30 min and 1, 2, 4, 8, 12, 16, 20 and 24 h.Dynamic scintigraphic acquisitions showed predominant hepatic uptake, and ex vivo counting indicated a long circulation time of labelled nanocapsules, with a half-life of 21+/-1 min for (99m)Tc and 22+/-2 min for (188)Re. Very weak urinary elimination was observed, indicating good stability of (99m)Tc and (188)Re labelling.(99m)Tc/(188)Re-SSS nanocapsules can be obtained with high yield and satisfactory radiochemical purity. The biodistributions of (99m)Tc/(188)Re-labelled nanocapsules are close to those of classical PEG-coated particles and show good stability of (188)Re/(99m)Tc-SSS labelling.

Previous studies have shown that the use of Lipiodol UltraFluid (LUF) emulsified with water leads to an increase in the tumoral uptake of iodine I 131-labeled LUF and reduced pulmonary uptake. Although emulsions containing LUF are currently used for chemoembolization of hepatocellular carcinomas (HCCs), this approach is impossible with intraarterial radiation therapy (RT) because of the problems of radiation protection linked to instability of the emulsions. The aims of this study were to develop stabilized emulsions of radiolabeled LUF of different particle sizes and viscosities and to study its biodistribution in rats with HCC.An emulsifier made of polyethylene glycol and hydrogenated castor oil was used to stabilize emulsions containing water and technetium Tc 99m-labeled Super Six Sulfur LUF. The various emulsions were injected in the hepatic arteries of rats with HCC. Twenty-four hours after injection, the rats were killed and the liver, tumor, and lungs were removed to perform ex-vivo gamma-counting to quantify tumoral, hepatic, and pulmonary uptake.Emulsions of oil in water and water in oil of different viscosities (0.68-1.06 Pa.S) and particle size distributions (21-45 mum) were prepared and kept stable for more than 24 hours. Whatever the type of emulsion, the observed effect on tumoral uptake was the opposite of that expected. Indeed, a decrease in tumoral activity was observed (P.05 in three of five cases) and a tendency toward increased pulmonary activity was observed (P.05 in two of five cases) rather than any significant decrease.This study made it possible to develop emulsions of radiolabeled iodized oil that remain stable for more than 24 hours. However, studies of biodistribution in rats with HCC failed to demonstrate any improvement in tumoral targeting, but rather showed a decrease in tumoral uptake that renders this approach impractical for intraarterial radiolabeled iodized oil RT as well as for intraarterial iodized oil chemoembolization. These results may possibly be explained by the use of an emulsifier containing lipophilic and hydrophilic components that modify the properties of LUF.

Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature. Dig Dis Sci 2010;55:2450–2458. [6] Garin E. Radioembolisation of hepatocellular carcinoma patients using yttrium-90 labelled microspheres: towards a diffusion of the technique? Eur J Nucl Med 2011;38:2114–2116. Etienne Garin⇑ Yan Rolland Eveline Boucher Comprehensive Cancer Center Eugene Marquis, CS 44229, 35042 Rennes, France ⇑Corresponding author. E-mail address: e.garin@rennes.unicancer.fr Letters to the Editor

Background Although intra-arterial radiation therapy with 1 3 1 I-lipiodol is a useful therapeutic approach to the treatment of hepatocellular carcinoma, various disadvantages limit its use. Aim To describe the development of a method for the labelling of lipiodol with 1 8 8 Re-SSS ( 1 8 8 Re (S 2 CPh)(S 3 CPh) 2 complex) and to investigate its biodistribution after injection into the hepatic artery of rats with hepatoma. Methods 1 8 8 Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 1 8 8 Re, in cold lipiodol. The radiochemical purity (RCP) of labelling was checked immediately. The 1 8 9 Re-SSS lipiodol was injected into the hepatic artery of nine rats with a Novikoff hepatoma. They were sacrificed 1, 24 and 48 h after injection, and used for ex vivo counting. Results Labelling of 1 8 8 Re-SSS lipiodol was achieved with a yield of 97.3 ′ 2.1%. The immediate RCP was 94.1 ′ 1.7%. Ex vivo counting confirmed a predominantly hepatic uptake, with a good tumoral retention of 1 8 8 Re-SSS lipiodol, a weak pulmonary uptake and a very faint digestive uptake. The tumour/non-tumoral liver' ratio was high at 1, 24 and 48 h after injection (2.9 ′ 1.5, 4.1 ′ 4.1 and 4.1 ′ 0.7, respectively). Conclusions Using the method described here, 1 8 8 Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. The biodistribution in rats with hepatoma indicates a good tumoral retention of 1 8 8 R e-SSS lipiodol associated with a predominant hepatic uptake, a weak pulmonary uptake and a very faint digestive uptake. This product should be considered for intra-arterial radiation therapy in human hepatoma.

The intra-arterial administration of 131I-lipiodol is a therapeutic approach increasingly used for the treatment of inoperable hepatocellular carcinomas. This technique has even become the reference treatment for hepatocellular carcinomas with portal thrombosis and is the only effective treatment to reduce the risk of recurrence among patients who could benefit from surgical operation. Currently, few data have been published concerning the levels of exposure for personnel carrying out this type of treatment. We undertook a dosimetric study targeted mainly on the exposure of the person performing the injection of 131I-lipiodol to show that this treatment can be carried out with an exposure at the extremities distinctly lower than the regulatory annual threshold by using simple means of radioprotection. The point of puncture was carried out at the level of left femoral artery, the preparation and injection of the therapeutic dose was carried out extemporaneously by the nuclear medicine specialist using a 10 ml syringe (for an injected volume of 4 ml) fitted with an adapted syringe protector. The injection was carried out as rapidly as possible under scopic control while avoiding reflux, with compression carried out by the radiologist. This study comprises 52 intra-arterial injections of 131I-lipiodol (2016+/-92 MBq). For the nuclear medicine specialists, 52 measurements were carried out at the level of the thorax and 41 on the fingers. For the radiologists, 22 measurements were carried out at the level of the thorax and six on their index fingers; nine measurements were carried out at the level of the thorax for the technologist and four at the level of the thorax for the stretcher bearer. For the nuclear medicine specialists, the average dose received at the level of the fingers varies between 140 and 443 microSv (according to the fingers) and the average dose at the thorax is 17 microSv. For the radiologists, the average dose received is 215 microSv at the level of the fingers and 15 microSv at the thorax. These results show that the administration of high therapeutic activities of 131I-lipiodol can be carried out for the exposed personnel with a dose at the level of the fingers much lower than the European regulatory limit of 500 mSv.

Results: For 2x2x3mm3 crystals we achieve a CTR of 108±5ps FWHM at an energy of 511keV. Under the same experimental conditions an increase in crystal length to 5mm deteriorates the CTR to 123±7ps FWHM, 10mm to 143±7ps FWHM and 20mm to 176±7ps FWHM. This degradation in CTR is caused by the light transfer efficiency (LTE) and light transfer time spread (LTTS) in the crystal. To quantitatively understand the measured values, we developed a Monte Carlo simulation tool in MATLAB incorporating the timing properties of the photodetector and electronics, the scintillation properties of the crystal and the light transfer within the crystal simulated by SLITRANI. In this work, we show that the predictions of the simulation are in good agreement with the experimental data. We can also derive what is the best time estimator for the case of fully digital readout as a function of the SiPM characteristics, level of dark count noise and scintillation signal shape. Conclusions: Very good timing resolution has been obtained and the influence of the crystal length has been quantitatively assessed. Moreover these data allowed us to validate a very detailed Monte Carlo model that helps us now, by switching on and off the different contributions to understand their relative influence and to optimize the overall timing resolution. Future investigations will be on the role of photonic crystals to further improve these results.

Planar (99)Tc(m)-methoxyisobutylisonitrile ((99)Tc(m)-MIBI) scintimammography has been used for several years to detect breast cancer tumours, but with low sensitivity for small lesions. Results of tomoscintimammography studies have not been conclusive. We conducted a phantom study to compare the detection of small-sized tumours with planar versus tomoscintigraphic images. We used a data spectrum anthropomorphic fillable breast phantom with two 9.8 mm and 12.4 mm spheres superficially or deep in the breast compartment with sphere/breast activity ratios varying from 3 to 6. We acquired planar and 180 degrees tomoscintigraphic images in each configuration using a double head standard gamma camera. In certain cases we varied different parameters (64x64 matrix or 360 degrees rotation) in a second series of tomoscintigraphic acquisitions. We simultaneously used filtered back-projection reconstruction (FBP) and iterative reconstruction (IR). Planar images were shown by the sphere in 10 out of 25 cases. Tomoscintigraphic images were shown by the sphere in nine out of 25 cases with FBP and in 18 out of 25 with IR. There was a significant difference between IR and FBP (P0.01) and between planar and IR images (P0.01), but no significant difference between planar and IR images. The noise/signal ratio was lower with planar images than with the two types of reconstruction (P0.05) but was not significantly different between the two types of reconstruction. Contrast was lower on planar images than on the two types of reconstruction (P0.05) and was also better on IR than on FBP images (P0.05). Granularity was lower for planar images than for reconstruction images (P0.01) and also lower for IR than for FBP (P0.01). The tomoscintigraphic reconstructions acquired with a 64x64 matrix were only positive in four out of 10 cases, while they were positive in nine out of 10 with a 128x128 matrix. We concluded that, in this phantom study, tomoscintimammography with IR provides a significant improvement in the detection of small-sized breast tumours compared with planar images. In addition, for tomoscintigraphic images, a 128x128 matrix is preferable to a 64x64 matrix. Those results have, of course, to be confirmed in vivo in a large population of patients with small-sized breast lesions.

A 66-year-old woman was diagnosed with vaginal melanoma. Sentinel node mapping was performed using Tc sulfur colloid. Planar scintigraphic acquisitions detected 2 sentinel nodes in the right external iliac region, which were laparoscopically removed with an anterior vaginectomy. Sentinel node mapping is feasible in cases of vaginal melanoma.

We conducted a prospective evaluation of somatostatin receptor scintigraphy (SRS) for the diagnosis of recurrent vesicular or papillary thyroid carcinoma in 16 patients with no detectable iodine uptake. SRS was performed 1, 4 and 24 h after intravenous injection of 137–200 MBq of indium-111 pentetreotide. Results were interpreted in terms of assumed presence of tumoral tissue: there were three true-positives (19%), one false-positive (6%) and 12 false-negatives (75%). The three true-positive patients had multiple lesions visible on computerized tomography. SRS was negative in all patients with a high thyroglobulin level alone. In addition, we analyzed the consequences of interpretative criteria and somatostatin receptor expression variability for SRS positivity as well as the risk of false-positives. We conclude that when iodine uptake cannot be demonstrated in patients with suspected recurrence of differentiated thyroid carcinoma, SRS would not appear to contribute to diagnosis, and that interpretative criteria commonly used for tumours with a high receptor density may be too restrictive for tumours with a low receptor density.

We conducted a prospective study in order to evaluate the contribution of technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocyte scintigraphy to the diagnosis and follow-up of osteomyelitis in the diabetic foot. The study was conducted between October 1992 and November 1996 and included 42 patients (30 men and 12 women; mean age 63 years) with diabetes mellitus (type 1, n = 22, type 2, n = 20) who had a total of 56 diabetic foot ulcers. The initial exploration included standard radiography, three-phase bone scintigraphy and 99mTc-HMPAO labelled leucocyte scintigraphy (HMPAO-LS), performed within a 3-day interval. For the 56 ulceration sites, 26 cases of osteomyelitis were diagnosed: ten on the basis of radiographic and histological/bacteriological criteria after bone biopsy, 11 after radiographic follow-up and five on the basis of biopsy results alone. No osteomyelitis was present at 30 sites, there were seven cases of cellulitis. The sensitivity and specificity of 99mTc-HMPAO-LS were 88.4% and 96.6% respectively (23 true-positives, 29 true-negatives, one false-positive, three false-negatives). The accuracy of radiography, 99mTc-methylene diphosphonate and HMPAO-LS was 69.6%, 62.5%, and 92.9%, respectively. Follow-up scintigraphy (n = 14) 4 months after initial diagnosis and 1 month after antibiotic withdrawal confirmed cure of osteomyelitis despite the absence of complete clinical regression of the ulcers. In conclusion, 99mTc-HMPAO labelled leucocyte scintigraphy was found to be an excellent method for the diagnosis of osteomyelitis in the diabetic foot. It can contribute to follow-up, particularly when clinical regression of perforating ulcers is incomplete and cure of osteomyelitis must be confirmed in order that antibiotic treatment may be discontinued.

Abstract 906 Background: Consolidation using radioimmunotherapy (RIT) is a promising approach for elderly patients with diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem-cell transplantation. RIT using fractionated injections of 90Y-epratuzumab tetraxetan (Immunomedics, Inc.), a radiolabeled humanized anti-CD22 antibody, has been evaluated in relapsed patients with indolent or aggressive non-Hodgkin lymphoma (NHL), providing long-term disease control with manageable hematologic toxicities (Morschhauser et al., J Clin Oncol. 2010;28(23);3709-16). A French phase II trial sponsored by the LYSA group now assessed front-line treatment using fractionated RIT with 90Y-epratuzumab tetraxetan as consolidation therapy after R-CHOP in previously untreated elderly (age >60 years) patients presenting with stage I/II bulky or stage III/IV DLBCL. Methods: The trial included 6 courses of R-CHOP delivered q2wks followed by 2 infusions of 90Y-epratuzumab tetraxetan (2 × 15 mCi/m2 [555 MBq/m2], 7 days apart), 8 wks later. Patients were enrolled at time of diagnosis. Results: From October 2008 to December 2010, 75 patients (41 males, 34 females) have been accrued prospectively at 19 French institutions. The median age was 69 (range, 60–79 years); 57 patients (76.0%) were Ann Arbor stage III/IV. Seventy-one of the 75 completed 6 courses of R-CHOP-14 and 61/75 (81.2%) were eligible for RIT. Thus, 14 patients were considered ineligible for RIT because of R-CHOP toxicity (N= 5), progressive disease (PD, N=3), patient refusal (N=3), or concomitant illness (N=3). RIT toxicity consisted of grade 3–4 hematologic toxicity in 51/61 patients (83.6%): grade 3–4 neutropenia in 46 (75.4%), grade 3–4 anemia in 15 (24.6%), and grade 3–4 thrombocytopenia in 47 (77.0%), with a nadir at 42, 48, and 43 days after RIT and a median duration of 18, 5, and 17 days, respectively. Following RIT, RBC and/or platelet transfusions were given to 31 patients (50.8 %). Serious febrile neutropenia was observed in 13 cases (17.3 %) after R-CHOP and in 3 patients (4.9%) following RIT. RIT's severe non-hematologic toxicity consisted of grade 4 gastrointestinal in 1 patient (1.6 %) and grade 4 infection in 3 (4.9%). No patient had mucositis after RIT. In the follow-up, 2 patients (2.6%) developed myelodysplastic syndrome 5 and 20 months after RIT. Using the 1999 International Workshop for Response Criteria for NHL (Cheson 1999), the overall response rate (ORR) after 6 × R-CHOP14 was 94.6% (71/75); 52 patients (69.3%) achieved CR/CRu and 19 (25.3%) had a partial response (PR). Among the 4 remaining patients, one had stable disease and 2 had PD; no assessment was obtained in the other. In an intention-to-treat analysis, CR/CRu rate after 6 × R-CHOP14 followed by RIT was 72.0% (N=54). Seven patients (9.3%) remained in PR and 8 (10.7%) progressed (2 patients previously in PR with PET-positive findings, 3 previously in CRu, including 1 PET-positive, and 3 in PD before RIT and then ineligible for RIT). No response assessment was obtained in the 6 others ineligible for RIT. At a median follow-up of 24 months (range, 1–46), 18 patients experienced lymphoma progression and/or a related death, yielding an estimated 2-year event-free-survival (EFS) of 73.3% (60.7-82.5%) and an estimated 2-year overall survival (OS) of 83.2% (71.4-90.4%). For the 61 patients who received 6 courses of R-CHOP followed by RIT consolidation, ORR was 91.8% (56/61); 50 patients (81.9%) achieved CR/CRu. Eight of 16 patients (50.0%) who had less than a CR/CRu with R-CHOP converted to CR/CRu after RIT. According to a PET analysis (Cheson 2007; N=55), 12 of the 24 patients (50.0%) who were not PET-negative after R-CHOP improved their metabolic response after RIT, resulting in a CR rate of 72.7%. Among these 61 patients, 12 experienced progression and/or a related death, yielding an estimated 2-year EFS of 78.7% (65.1–87.4%) and an estimated 2–year OS of 90.1% (77.7–95.8%). Conclusions: This phase II study clearly shows that fractionated RIT with 90Y-epratuzumab as a consolidation therapy after 6 × R-CHOP-14 is feasible and tolerable in elderly untreated DLBCL patients with advanced disease. RIT markedly improved response status observed after 6 × R-CHOP14. EFS data achieved with R-CHOP plus RIT compare favourably with those achieved with R-CHOP alone in the same patient population. Disclosures: Wegener: Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

247 Background: In case of non resectable HCC, radioembolization and sorafenib (S) are therapeutic options respectively for intermediate and advanced stages. In some other cancers, there is an increase of efficacy when external beam radiotherapy is done concomitantly with systemic chemotherapy or targeted therapies. So we wondered if there could be a synergistic or an additive activity when S is combined with a radionuclide. Methods: Hepatoma cell lines N1S1 (murine HCC), HepG2 (human hepatoblastoma) and HepaRG (human HCC) were treated with increasing concentrations of rhenium-188 (188Re) or S. On each cell line, we have studied the cellular toxicities of S and 188Re using Tetrazolium dye test, extra-cellular medium LDH level and morphologic analysis. This was done for different dosage of S and 188Re. We measured the lethal concentration killing 25% of cells (LC25) with the results of the Tetrazolium dye test. Secondly, we looked for synergy or additivity on cellular toxicity of these two compounds according to cell lines by combined treatment. Synergy or additivity was estimated with the combination index (CI) method (synergy if CI lower than 1, additivity if CI = 1, antagonism if CI upper to 1) based on the Tetrazolium dye test’s results. Results: Monotherapy dose-dependent toxicities were observed for all three cell lines with 188Re and for the N1S1 and HepG2 cell lines only with S. Combined treatment with 188Re and S showed synergy on HepaRG and N1S1 cell lines and additivity on the HepG2 cell line. Conclusions: The additive, and even synergistic, interest of a combined treatment with 188Re and S is demonstrated in vitro (for the first time to our knowledge) on hepatoma cell lines. This results, in particular for the HepaRG cell line (human HCC), could be explained by the down-regulation of the hepatic drug transporters which are responsible for the Sorafenib efflux in case of simultaneous DNA damages due to a radionuclide exposition. This promising approach now needs to be confirmed in vivo. [Table: see text]

e14573 Background: Portal vein tumoral thrombosis is a pejorative and a frequent complication of hepatoculluar carcinoma (HCC). PVT shows as the primary tumour, an arterial hypervascularization; hi...

Abstract 855 Aim: Despite its often indolent clinical course, follicular lymphoma (FL) is a heterogeneous disease. Current criteria for early identification of patients with a poor prognosis are suboptimal - the FLIPI and F2 index are insufficient prognostic markers for individual patients and the limitations of post-treatment conventional response criteria have long been acknowledged. FL shows increased FDG uptake, but unlike DLBCL, minimal data exist about the role of PET-CT in response assessment. We have used the prospective conventional response assessment and 42 month patient follow-up in the PRIMA (Primary Rituximab and Maintenance, Salles et al., ASCO 2010, Abstr#8004) study as a platform for analysis of the utility of PET-CT in FL. Methods: The PRIMA database was interrogated and investigators surveyed to identify PET-CT scans performed during staging and induction response assessment. Single modality PET-only scans were not eligible for inclusion. Local PET interpretation (positive + or negative -) was used to explore associations with patient outcomes. The primary endpoint was PFS from PRIMA registration. Results: 277 PET-CT scans on 160 patients from 40 centres were identified. Baseline patient characteristics did not differ from the overall PRIMA patient population. Positive PET-CT scans were recorded in 119/120 (99%) at diagnosis, 11/33 (33%) interim restaging scans and 32/124 (26%) post induction treatment (R-CHOP or R-CVP). There was significant correlation between PET-CT result and conventional response assessment at the end of immunochemotherapy (p With a median follow-up of 42 months, a significantly inferior actuarial 3yr PFS was observed in post-treatment PET+ vs. PET- patients (Figure 1): 32% (95% CI 17–48%) vs. 74% (95% CI 63–82%) (log rank p Using proportional hazard regression analysis, both conventional response (overall p=0.0002) and PET+ status (HR 2.8 p=0.0007) were significant predictors of inferior PFS. However, the predictive power of conventional response assessment was limited to non-responders: SD/PD vs. CR/CRu (HR 6.5, p When only patients randomised for the maintenance element of the PRIMA study were considered, post-treatment PET+ (15/59) remained predictive of 3yr PFS (27 vs. 69%, HR 3.1, p=0.005) in the observation arm, but post-treatment PET+ (9/47) was not significantly associated with an adverse outcome in patients receiving rituximab maintenance (3-year PFS 56 vs. 81%, HR 2.2, p= 0.18). In a multivariate Cox model including responding patients the following factors were negative predictors of PFS: post-treatment PET+ (HR 3.1 p Conclusion: This PRIMA sub-study demonstrates that post-treatment PET-CT is a powerful predictor of PFS that complements conventional response evaluation after first line immunochemotherapy for FL. Patients who are PET- can expect a prolonged PFS whether in conventional CR or PR, but for those remaining PET+, with a median 19 month PFS, the disease cannot be characterized as indolent. Future clinical trials should evaluate an FDG PET-CT response adapted approach focused on improving outcomes for this group. Disclosures: Seymour: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shpilberg:Roche: Consultancy, Honoraria.