dAcquisition setting optimization and quantitative imaging for 124I studies with the Inveon microPET-CT system

International audienceABSTRACT: BACKGROUND: Noninvasive multimodality imaging is essential for preclinical evaluation of the biodistribution and pharmacokinetics of radionuclide therapy and for monitoring tumor response. Imaging with nonstandard positron-emission tomography [PET] isotopes such as 124I is promising in that context but requires accurate activity quantification. The decay scheme of 124I implies an optimization of both acquisition settings and correction processing. The PET scanner investigated in this study was the Inveon PET/CT system dedicated to small animal imaging. METHODS: The noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction). RESULTS: Optimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert. CONCLUSIONS: The optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging

Patient-specific biokinetics evaluation based on multiple SPECT images or hybrid planar/SPECT technique using OEDIPE 3D personalized dosimetry software: development and application

International audienceBackground:With the development of targeted radionuclide therapy, it has become increasingly necessary to develop comprehensive tools to compute 3D personalized dosimetry accounting for patient-specific biokinetics. For that purpose new functionalities were developed in OEDIPE software, to insure compatibility with different sets of patient images (multiple 3D images, multiple planar/SPECT images).Materiel & Method:Two new processes of image analyses were implemented and adapted to multiple time-point 3D images (SPECT/CT or PET/CT), and multiple planar images associated to a single SPECT/CT. Both processes enable recovering time-activity data for each volume of interest (VOI). A biokinetic module was developed to fit time-activity curves (TACs) to the obtained data and to calculate the cumulated activity in the VOIs. To evaluate the robustness of these developments, multiple SPECT/CT and planar images of a JASZCZAK phantom containing I-131 were consecutively acquired at different time-points. Cumulated activity of I-131 was estimated in each sphere using: (i) the SPECT/CT images only, and (ii) the planar series associated to one SPECT/CT out of the six available images, to quantify the influence of the selected time-point at which the SPECT was acquired. Results were compared with the known cumulated activity. To test the clinical applicability of these developments, cumulated activities in lesions and in the lungs of a patient treated for differentiated thyroid cancer were estimated using four planar images and a SPECT/CT scan acquired after I-131 administration. Whole-body retention data combined with SPECT activities were used to generate biokinetic data to compare with.Results:Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient were similar with those derived from the method based on the whole-body retention data combined with SPECT activities.Conclusion:These new features of OEDIPE allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling efficient patient-specific internal dosimetry without the need for external software to estimate the cumulated activities in different VOIs.Keywords:targeted radionuclide therapy (TRT); radiopharmaceutical therapy (RPT); patient-specific biokinetics; 3D personalized internal dosimetry; Monte Carlo-based radiation transport code; OEDIPE dosimetric software; hybrid planar-SPECT dosimetr

Performance Measurements of the microPET FOCUS 120 for Iodine-124 Imaging

This study aimed to evaluate the performance of the microPET FOCUS 120 for 124I in terms of counting rate capability and image quality using the NEMA NU 4-2008 methodology. Scanner sensitivity was measured for 124I for comparison and reached 75 cps/kBq, respectively, with the usual 350-650 keV energy window (EW) and 6 ns time window (TW). The noise equivalent count rate (NECR) index was defined as: NECR = RT2/(RP+RGP) (T = true, P = prompt, GP = γ-prompt). A rat phantom maximum NECR of 48 kcps was obtained for the 250-590 keV EW with 6 ns TW. An almost identical maximum NECR of 43 kcps was recorded for 350-590 and 350-650 keV EW and 6 ns TW. The 2 ns TW reduced the sensitivity and NECR by 40-50% for all EW. The mouse phantom NECR study was limited because of the maximum available activity concentration of 124I. The 250-590 keV EW showed the largest scatter and γ-prompt plus scatter fractions with 25.7% and 43%, respectively, for the rat phantom and 12.2% and 27% for the mouse phantom. With the 350-590 keV EW, these fractions decreased to 20% and 33.5% for the rat phantom and to 10% and 21% for the mouse phantom. The image quality was investigated with the NEMA NU 4-2008 dedicated phantom for four (two analytic and two iterative) 2D or 3D reconstruction methods. The lowest spillover ratios (SOR) for the phantom non-emitting regions were obtained for the 350-590 and 350-650 keV EWs. Recovery coefficients (RC) of the hot rods were the highest for the 350-590 keV EW except for the 1 mm rod. Scatter correction led to a large decrease in RC. The combination of the 350-590 keV EW with 6 ns TW appeared to be a good compromise between counting rate capability and image quality for the FOCUS 120, especially when maximum a posteriori reconstruction was used without scatter correction. Moreover this combination enabled the best quantification with an error as low as 0.36%

Early angiogenesis detected by PET imaging with 64Cu-NODAGA-RGD is predictive of bone critical defect repair

International audienc

Cleaved CD31 as a target for in vivo molecular imaging of inflammation

International audienceAbstract There is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99m Tc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [ 18 F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99m Tc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99m Tc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99m Tc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [ 18 F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99m Tc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99m Tc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes

Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using 111In-tilmanocept

Abstract Background Atherosclerotic plaque phenotypes are classified based on the extent of macrophage infiltration into the lesions, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The mannose receptor (MR) is over-expressed in activated macrophages. Tilmanocept is a tracer that targets MR and is approved in Europe and the USA for the detection of sentinel lymph nodes. In this study, our aim was to evaluate the potential of 111In-labelled tilmanocept for the detection of MR-positive macrophages in atherosclerotic plaques of apolipoprotein E-knockout (ApoE-KO) mouse model. Methods Tilmanocept was labelled with 111In. The labelling stability and biodistribution of the tracer was first evaluated in control mice (n = 10) 1 h post injection (p.i.). For in vivo imaging studies, 111In-tilmanocept was injected into ApoE-KO (n = 8) and control (n = 8) mice intravenously (i.v.). The mice were scanned 90 min p.i. using a dedicated animal SPECT/CT. For testing the specificity of 111In-tilmanocept uptake in plaques, a group of ApoE-KO mice was co-injected with excess amount of non-labelled tilmanocept. For ex vivo imaging studies, the whole aortas (n = 9 from ApoE-KO and n = 4 from control mice) were harvested free from adventitial tissue for Sudan IV staining and autoradiography. Cryosections were prepared for immunohistochemistry (IHC). Results 111In radiolabelling of tilmanocept provided a yield of greater than 99%. After i.v. injection, 111In-tilmanocept accumulated in vivo in MR-expressing organs (i.e. liver and spleen) and showed only low residual blood signal 1 h p.i. MR-binding specificity in receptor-positive organs was demonstrated by a 1.5- to 3-fold reduced uptake of 111In-tilmanocept after co-injection of a blocking dose of non-labelled tilmanocept. Focal signal was detected in atherosclerotic plaques of ApoE-KO mice, whereas no signal was detected in the aortas of control mice. 111In-tilmanocept uptake was detected in atherosclerotic plaques on autoradiography correlating well with Sudan IV-positive areas and associating with subendothelial accumulations of MR-positive macrophages as demonstrated by IHC. Conclusions After i.v. injection, 111In-tilmanocept accumulated in MR-expressing organs and was associated with only low residual blood signal. In addition, 111In-tilmanocept uptake was detected in atherosclerotic plaques of mice containing MR-expressing macrophages suggesting that tilmanocept represents a promising tracer for the non-invasive detection of macrophages in atherosclerotic plaques

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE−/− mice

International audienceAutoradiography of 64 Cu-labelled nanostructured lipid carriers (NLC) and Oil Red O histology (neutral lipids staining) of aortas showed significant particle uptake in atherosclerotic lesions 24 h after injection in ApoE −/− mice atherosclerotic models. Produced by well-controlled and up-scalable high pressure homogenization, NLC could present similar features than lipoproteins, and be used as synthetic mimetics to convey drugs and contrast agents to atherosclerotic lesions

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE-/- mice.

International audienceNanostructured lipid carriers (NLC) might represent an interesting approach for the identification and targeting of rupture-prone atherosclerotic plaques. In this study, we evaluated the biodistribution, targeting ability and safety of 64Cu-fonctionalized NLC in atherosclerotic mice. 64Cu-chelating-NLC (51.8±3.1 nm diameter) with low dispersity index (0.066±0.016) were produced by high pressure homogenization at tens-of-grams scale. 24 h after injection of 64Cu-chelated particles in ApoE-/- mice, focal regions of the aorta showed accumulation of particles on autoradiography that colocalized with Oil Red O lipid mapping. Signal intensity was significantly greater in aortas isolated from ApoE-/- mice compared to wild type (WT) control (8.95 [7.58, 10.16]×108 vs 4.59 [3.11, 5.03]×108 QL/mm2, P < 0.05). Moreover, NLC seemed safe in relevant biocompatibility studies. NLC could constitute an interesting platform with high clinical translation potential for targeted delivery and imaging purposes in atherosclerosis

MERAIODE: A Phase II Redifferentiation Trial with Trametinib and 131 I in Metastatic Radioactive Iodine Refractory RAS Mutated Differentiated thyroid Cancer

International audienceAbstract Purpose: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. Patients and Methods: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion &gt; 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. Results: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients. Conclusions: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients