Etienne Garin

Predictive Value of 18F-FDG PET and Somatostatin Receptor Scintigraphy in Patients with Metastatic Endocrine Tumors

The treatment of metastatic neuroendocrine tumors depends on the aggressiveness of the disease. We wanted to know whether 18F-FDG PET and somatostatin receptor scintigraphy (SRS) can predict early disease progression and patient survival. Methods: 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 18F-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. Results: 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 18F-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 18F-FDG PET–positive patients had early progressive disease (14/15, vs. 2/23 18F-FDG PET–negative patients), and most SRS-negative patients had early progressive disease (9/11, vs. 7/27 SRS-positive patients); 18F-FDG PET gave excellent negative and positive predictive values of 91% and 93%; 18F-FDG PET results correlated with progression-free survival (P < 0.001) and overall survival (P < 0.001) even when only low-grade tumors were considered. SRS was associated with progression-free survival (P < 0.001) and overall survival (P < 0.03). At multivariate analysis, only 18F-FDG PET was predictive of progression-free survival. Conclusion: 18F-FDG PET exhibits excellent predictive values for early tumor progression. 18F-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.

Dosimetry Based on 99mTc-Macroaggregated Albumin SPECT/CT Accurately Predicts Tumor Response and Survival in Hepatocellular Carcinoma Patients Treated with 90Y-Loaded Glass Microspheres: Preliminary Results

Radioembolization of liver cancers using 90Y-loaded microspheres is experiencing more widespread use. However, few data are available concerning the doses delivered to the tumors and the healthy liver. This retrospective study was conducted to calculate the tumor dosimetry (planned tumor dose [Tplan D]) and nontumor dosimetry in patients treated by 90Y-loaded glass microspheres and determine whether tumor dosimetry could predict response and survival. Methods: Thirty-six patients with hepatocellular carcinoma (HCC), including 16 with portal vein thrombosis (PVT), were treated with 90Y-loaded glass microspheres. The Tplan D and the dose delivered to the injected healthy liver were calculated using a quantitative analysis of the 99mTc-macroaggregated albumin (99mTc-MAA) SPECT/CT exam. Responses were assessed after 3 mo, using the criteria of the European Association for the Study of the Liver. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier tests. Results: The response rate was 69% for the overall population and 75% for the PVT patients. The dose delivered to the tumor was the only parameter associated with response with multivariate analysis (P = 0.019). A threshold Tplan D value of 205 Gy was predictive of response, with a sensitivity of 100% and an accuracy of 91%. Quantitative 99mTc-MAA SPECT/CT allowed us to increase the injected activity for 4 patients with large lesions. PFS was only 5.2 mo and OS 9 mo when using a Tplan D of less than 205 Gy versus 14 mo (P = 0.0003) and 18 mo (P = 0.0322), respectively, with a Tplan D of 205 Gy or more. Conclusion: Quantitative 99mTc-MAA SPECT/CT is predictive of response, PFS, and OS. Dosimetry based on 99mTc-MAA SPECT/CT can be used for the selection of patients and for an adaptation of treatment planning, especially in selected patients (particularly in the case of large tumors). These results also confirm the efficacy and safety of 90Y-loaded microspheres in treating HCC, even in the presence of PVT (and especially when 99mTc-MAA uptake is seen inside the PVT).

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

PurposeAlthough 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.MethodsWe studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using 18F-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.ResultsThe 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.ConclusionThese 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.

Clinical Feasibility of Fast 3-Dimensional Dosimetry of the Liver for Treatment Planning of Hepatocellular Carcinoma with 90Y-Microspheres

Several treatment strategies are used for selective internal radiation therapy with 90Y-microspheres. The diversity of approaches does not favor the standardization of the prescribed activity calculation. To this aim, a fast 3-dimensional (3D) dosimetry method was developed for 90Y-microsphere treatment planning and was clinically evaluated retrospectively. Methods: Our 3D approach is based on voxel S values (VSVs) and has been implemented in the software tool VoxelDose. VSVs were previously calculated at a fine voxel size. The time-integrated activity (TIA) map is derived from pretherapeutic 99mTc-macroaggregated-albumin SPECT/CT. The fine VSV map is resampled at the voxel size of the TIA map. Then, the TIA map is convolved with the resampled VSV map to construct the 3D dose map. Data for 10 patients with 12 tumor sites treated by 90Y-microspheres for hepatocellular carcinoma were collected retrospectively. 3D dose maps were computed for each patient, and tumoral liver and nontumoral liver (TL and NTL, respectively) were delineated, allowing the computation of descriptive statistics (i.e., mean absorbed dose, minimum absorbed dose, and maximum absorbed dose) and dose–volume histograms. Mean absorbed doses in TL and NTL from VoxelDose were compared with those calculated with the standard partition model. Results: The estimated processing time for a complete 3D dosimetry calculation is on the order of 15 min, including 10 s for the dose calculation (i.e., VSV resampling and convolution). An additional 45 min was needed for the semiautomatic and manual segmentation of TL and NTL. The mean absorbed dose (±SD) was 422 ± 263 Gy for TL and 50.1 ± 36.0 Gy for NTL. The comparison between VoxelDose and partition model shows a mean relative difference of 1.5% for TL and 4.4% for NTL. Results show a wide spread of voxel-dose values around mean absorbed dose. The minimum absorbed dose within TL ranges from 32 to 267 Gy (n = 12). The fraction of NTL volume irradiated with at least 80 Gy ranges from 4% to 70% (n = 10), and the absorbed dose from which 25% of NTL was the least irradiated ranges from 14 to 178 Gy. Conclusion: This article demonstrates the feasibility of a fast 3D dosimetry method for 90Y-microspheres and highlights the potential value of a 3D treatment planning strategy.

Comparison of Tc-99m-labelled antileukocyte fragment Fab' and Tc-99m-HMPAO leukocyte scintigraphy in the diagnosis of bone and joint infections: a prospective study.

Between January and July 1998, we conducted a prospective study to compare Tc-99m-labelled antigranulocyte monoclonal antibody fragment Fab′ (LEUKOSCAN®) scintigraphy versus Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HMPAO)-labelled leukocyte scintigraphy (HMPAO-LS) for the diagnosis of unselected patients with bone and joint infection. Twenty-three patients (16 men and 7 women; mean age, 67 years) with suspected bone infection were explored successively with bone scintigraphy, HMPAO-LS and LEUKOSCAN® scintigraphy. Thirty-two foci were studied (diabetic foot = 11, prosthetic material = 8, joint disease = 4, others = diagnosed in 18 cases, eight on the basis of bacteriological and histological examination of surgical or puncture specimens, with or without radiographic signs, and 10 on the basis of clinical course and radiographic findings. Overall sensitivity, specificity and accuracy were 86%, 72% and 78%, respectively, for LEUKOSCAN® scintigraphy (12 true positives (TP), 13 true negatives (TN), 5 false positives (FP), 2 false negatives (FN)), 93%, 100% and 96%, respectively, for HMPAO-LS (13TP, 18TN, 0FP, 1FN), and 100%, 17% and 53.3%, respectively, for bone scintigraphy. In this small series, LEUKOSCAN® scintigraphy was found to be less specific for the diagnosis of osteomyelitis than HMPAO-LS. In addition, the interpretation of LEUKOSCAN® scintigraphy is more difficult than HMPAO-LS for the diagnosis of bone infection in the diabetic foot, and would appear to be less discriminating for differentiating soft tissue infection from osteitis in the case of plantar perforating ulcers.

188Re-SSS lipiodol: radiolabelling and biodistribution following injection into the hepatic artery of rats bearing hepatoma.

BackgroundAlthough intra-arterial radiation therapy with 131I-lipiodol is a useful therapeutic approach to the treatment of hepatocellular carcinoma, various disadvantages limit its use. AimTo describe the development of a method for the labelling of lipiodol with 188Re-SSS (188Re (S2CPh)(S3CPh)2 complex) and to investigate its biodistribution after injection into the hepatic artery of rats with hepatoma. Methods188Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with 188Re, in cold lipiodol. The radiochemical purity (RCP) of labelling was checked immediately. The 188Re-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. ResultsLabelling of 188Re-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 188Re-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). ConclusionsUsing the method described here, 188Re-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 188Re-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.

Adjuvant Intraarterial Injection of 131I-Labeled Lipiodol After Resection of Hepatocellular Carcinoma : Progress Report of a Case-Control Study with a 5-Year Minimal Follow-up

Recurrences after resection of hepatocellular carcinoma are frequent. A single postoperative injection of 131I-labeled lipiodol in the hepatic artery was shown in 1999 by Lau and colleagues to be an effective adjuvant treatment, and those results were strengthened by our experience with a case-control study, reported in 2003. The goal of this paper is to update the 2003 results for a minimal follow-up of 5 y. Methods: Between January 1999 and September 2001, 38 patients were given an adjuvant postoperative intraarterial injection of 131I-lipiodol and were matched (for Okuda group and tumor size) with 38 patients who had undergone resection between January 1997 and January 1999 without postoperative treatment. The 2 groups were similar. Results: There were 28 recurrences in the control group and 22 in the 131I-lipiodol group (not statistically significant), and the mean time of recurrence was 21 and 26.5 mo, respectively, after surgery (statistically significant). The number of recurrences was lower in the first 2 y in the 131I-lipiodol group (statistically significant). Disease-free survival was better (P < 0.03) in the 131I-lipiodol group than in the control group (2-, 3-, and 5-y rates [±95% confidence interval] of 77% ± 7%, 63% ± 8%, and 42% ± 8.5%, respectively, for the 131I-lipiodol group vs. 47% ± 8%, 34% ± 8%, and 27% ± 8%, respectively, for the control group). Overall survival did not differ between the 2 groups (P = 0.09), even though there was a trend toward better survival in the 131I-lipiodol group (2-, 3-, and 5-y rates of 76% ± 7%, 68% ± 7.5%, and 51% ± 9%, respectively, vs. 68% ± 7.5%, 53% ± 8%, and 39% ± 8%, respectively, in the control group). Conclusion: With a longer follow-up, the results of this retrospective case-control study still favor a single postoperative injection of 131I-lipiodol. These retrospective findings point out the need for a large-scale, prospective, randomized study.

Lipid nanocapsules loaded with rhenium-188 reduce tumor progression in a rat hepatocellular carcinoma model.

Background Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC188Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC188Re-SSS in a chemically induced hepatocellular carcinoma rat model. Methodology/Principal Findings Animals were treated with an injection of LNC188Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and 188Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC188Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC188Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. Conclusions/Significance Overall, these results demonstrate that internal radiation with LNC188Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.

Utility of Quantitative 99mTc-MAA SPECT/CT for 90yttrium-Labelled Microsphere Treatment Planning: Calculating Vascularized Hepatic Volume and Dosimetric Approach

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 <6% for volumes ≥16 cm3) 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.