Characterization of the distribution, retention, and efficacy of internal radiation of 188Re-lipid nanocapsules in an immunocompromised human glioblastoma model.

Internal radiation strategies hold great promise for glioblastoma (GB) therapy. We previously developed a nanovectorized radiotherapy that consists of lipid nanocapsules loaded with a lipophilic complex of Rhenium-188 (LNC188Re-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise. The efficacy of LNC188Re-SSS treatment was optimized through the induction of a T-cell immune response in this model, as it is highly immunogenic. However, this is not representative of the human situation where T-cell suppression is usually encountered in GB patients. Thus, in this study, we investigated the efficacy of LNC188Re-SSS in a human GB model implanted in T-cell deficient nude mice. We also analyzed the distribution and tissue retention of LNC188Re-SSS. We observed that intratumoral infusion of LNCs by CED led to their complete distribution throughout the tumor and peritumoral space without leakage into the contralateral hemisphere except when large volumes were used. Seventy percent of the 188Re-SSS activity was present in the tumor region 24 h after LNC188Re-SSS injection and no toxicity was observed in the healthy brain. Double fractionated internal radiotherapy with LNC188Re-SSS triggered survival responses in the immunocompromised human GB model with a cure rate of 50 %, which was not observed with external radiotherapy. In conclusion, LNC188Re-SSS can induce long-term survival in an immunosuppressive environment, highlighting its potential for GB therapy.

New starch-based radiotracer for lung perfusion scintigraphy.

PURPOSE: In order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical. METHODS: Microparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures. RESULTS: Particle-size analysis, electron microscopy, and confocal microscopy were performed for microparticle characterisation, and gave a typical size distribution ranging from 7 to 63 microm, with a homogenous population of spherical or oval-shaped microparticles. Radiochemical purity exceeded 95%, and was stable for at least 8 h. When challenged with histidine and human plasma, labelling was also stable. Dynamic scintigraphic acquisitions and biodistribution studies conducted on healthy Wistar rats showed a tracer accumulation with more than 80% of the ID in the lungs after 15 min. CONCLUSIONS: With clinically significant characteristics such as a lung half-life of 3 h, a lung-to-vascular ratio of 900, and a lung-to-liver ratio of 90, starch-based microparticles exhibit all the qualities for an effective new lung perfusion agent.

Dual time point [18F]FLT-PET for differentiating proliferating tissues vs non-proliferating tissues.

PURPOSE: For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]FLT-PET for discriminating benign from malignant tissues. METHODS: Before any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [18F]FLT injection. Semiquantitative analyses of [18F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey's posttests were used to compare SUVmax of each site at the three time points. RESULTS: There was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35). CONCLUSION: [18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

For avid glucose tumors, the SUV peak is the most reliable parameter for [(18)F]FDG-PET/CT quantification, regardless of acquisition time.

BACKGROUND: This study is an assessment of the impact of acquisition times on SUV with [(18)F]FDG-PET/CT on healthy livers (reference organ with stable uptake over time) and on tumors. METHODS: One hundred six [(18)F]FDG-PET/CT were acquired in list mode over a single-bed position (livers (n = 48) or on tumors (n = 58)). Six independent datasets of different durations were reconstructed (from 1.5 to 10 min). SUVmax (hottest voxel), SUVpeak (maximum average SUV within a 1-cm(3) spherical volume), and SUVaverage were measured within a 3-cm-diameter volume of interest (VOI) in the right lobe of the liver. For [(18)F]FDG avid tumors (SUVmax ≥ 5), the SUVmax, SUVpeak, and SUV41% (isocontour threshold method) were computed. RESULTS: For tumors, SUVpeak values did not vary with acquisition time. SUVmax displayed significant differences between 1.5- and 5-10-min reconstruction times. SUV41% was the most time-dependent parameter. For the liver, the SUVaverage was the sole parameter that did not vary over time. CONCLUSIONS: For [(18)F]FDG avid tumors, with short acquisition times, i.e., with new generations of PET systems, the SUVpeak may be more robust than the SUVmax. The SUVaverage over a 3-cm-diameter VOI in the right lobe of the liver appears to be a good method for a robust and reproducible assessment of the hepatic metabolism.

Calibration test of PET scanners in a multi-centre clinical trial on breast cancer therapy monitoring using 18F-FLT.

UNLABELLED: A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results. MATERIAL AND METHODS: 11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated. RESULTS: There was no significant difference for dose calibrator measurements (median of difference -0.04%; min = -4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference -0.69%; min = -9.97%; max = +9.60%). CONCLUSION: No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.

American consensus recommendations for gastric scintigraphy: curve fitting with only a few points remains an easy and accurate method to obtain reliable and reproducible gastric emptying estimates.

BACKGROUND: In 2008, American consensus recommendations for performing gastric emptying (GE) scintigraphy were published. It was recommended that data are acquired only at 0, 1, 2, and 4 h and that the results are expressed as percentages of meal retention. Until now, it was established that the GE time-activity curves should have many points (every 10, 15, or 20 min) to reflect the GE process accurately and to be optimally adjusted by a mathematical model. In this study, we have evaluated the curve fitting using only a few points as proposed by the consensus protocol. MATERIALS AND METHODS: GE scintigraphy tests of 224 patients were retrospectively analyzed. Two curve fittings were done for each patient, either using data acquired every 20 min or using data acquired every hour. A comparison of these two methods was made based on the values of the computed GE parameters. RESULTS: We observed strong correlations between the two methods (r=0.81-0.99, P<0.05). Using the Bland-Altman analysis, more than 95% of the differences were included in the mean difference 95% confidence interval. The mean differences were weak with a relatively small SD and Cohen's k coefficients ranging from 0.84 to 0.93, indicating an excellent agreement between the two methods. CONCLUSION: Our results showed the feasibility and accuracy of curve fitting using only a few points. The curve fitting is easy to perform and allows the computation of reliable and reproducible parameters that reflect the whole GE process.

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 (LNC(188)Re-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 LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. METHODOLOGY/PRINCIPAL FINDINGS: Animals were treated with an injection of LNC(188)Re-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 (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-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 LNC(188)Re-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 LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment.