The effect of mannosylation of liposome-encapsulated indocyanine green on imaging of sentinel lymph node

Abstract

The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50% fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with d-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system.     

Apport de la TEMP/TDM pour la détection du ganglion sentinelle dans les cancers du col utérin et de l’endomètre

The sentinel lymph node procedure is still under evaluation for the management of cervical and endometrial carcinomas. The aim of our study was to determine the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) for preoperative sentinel lymph node mapping in uterine cancers. Sixty-eight patients with cervical (n = 42) or endometrial carcinoma (n = 26) underwent preoperative lymphoscintigraphy for sentinel node mapping. Sentinel node detection rate with conventional planar imaging was similar to that of SPECT/CT (87.1 versus 91.8 %) in the whole cohort. However, SPECT/CT detected a higher number of sentinel nodes in more than one third of patients, affected by either cervical or endometrial carcinoma. The rate of non or insufficiently contributive procedures (lack of uptake or unilateral uptake) in endometrial carcinomas was 47 % with conventional planar imaging, and 30 % with SPECT/CT. Sensitivity of both procedures for the detection of metastatic nodes was 81.8 %, compared to 100 % for the intraoperative combined detection (gamma probe sonde and blue dye). The impact of SPECT/CT for the sentinel lymph node detection in cervical and endometrial carcinomas needs further evaluation. Nevertheless, SPECT/CT may provide additional information when conventional planar imaging detects only unilateral uptake, may improve identification of atypical localizations, and facilitate surgical approach.     

Le ganglion sentinelle dans les cancers de la cavité orale : impact clinique et apport de l’imagerie hybride

ObjectivesWe report a prospective evaluation of the sentinel lymph node identification and biopsy in oral cavity cancer in order to assess the additional value of the single photon emission computed tomography-computed tomography (SPECT-CT).Patients and methodsThirteen patients with T1 or T2 clinical N0 oral cavity cancer were prospectively included. They first underwent a lymphoscintigraphy with planar imaging. A SPECT-CT was performed secondly. Finally, excised sentinel lymph nodes were screened according to a specific histological processing.ResultsThe scintigraphic detection rate was 100%, both with planar and SPECT/CT imaging. Dynamic and early images were predictive of the lymph node drainage territory for 11 patients (85%). An impact of SPECT/CT in 83% of cases was achieved with additional quantitative information in 58% cases and qualitative information in 58% cases. A greater sensibility was also pointed out for level 1 sentinel lymph nodes, close to the injection site. Once, an occult metastasis was revealed by the histological analysis of the sentinel lymph nodes.ConclusionRadioisotopic sentinel lymph node technique for oral cavity cancers allowed determining neck node status for all patients. Ninety-two percent of them were spared from a radical neck dissection or radiotherapy. Preoperative detection of sentinel lymph node is optimised in most cases by hybrid imaging procedure. Anatomical data provided by hybrid imaging are useful for surgery.     

Immunotherapeutic effects of chitin in comparison with chitosan against Leishmania major infection

Chitin and chitosan microparticles (MPs) are important immune system stimulators. The aim of this study was to evaluate the protective effects of these compounds in comparison with each other against Leishmania infection in BALB/c mice infected with Leishmania major (L. major).Female BALB/c mice were injected subcutaneously with 2 × 10⁵ promastigotes. Chitin and/or chitosan MPs (< 40 μm) were subcutaneously injected in the BALB/c mice with two-day intervals until two weeks. Mice in all groups were sacrificed at 12 weeks post-infection. Enumeration of viable parasites was performed using limiting dilution assay. Furthermore, the animals (5 mice/group) were sacrificed two weeks post-infection. The lymph node cells were isolated and the effects of the chitinous MPs on the proliferation and production of cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were determined. The mean sizes of lesions were significantly smaller in chitin (0.6 ± 0.12 mm) and chitosan treated groups (1.2 ± 0.8 mm) than in the control group (6.2 ± 1.7 mm) (P < 0.05). The parasite load in the lymph nodes of the treated mice was significantly lower than that in the lymph nodes of controls (1.31 × 10⁶ vs 8.24 × 10⁷ parasite/lymph node [P = 0.032] and 7.49 × 10⁶ vs 8.24 × 10⁷ parasite/lymph node [P = 0.05] for chitin and chitosan MPs treatment, respectively). We found that chitinous MPs induced cell proliferation and that chitin but not chitosan increased TNF-α and IL-10 production. Chitin appears that it has more effect than chitosan against leishmaniasis. The current study revealed that chitinous MPs had significant activity against L. major and could be considered as new therapeutic modality in leishmaniasis.     

Novel cancer-targeting SPECT/NIRF dual-modality imaging probe 99mTc-PC-1007: Synthesis and biological evaluation

Synthesis, characterization, in vitro and in vivo biological evaluation of a heptamethine cyanine based dual-mode single-photon emission computed tomography (SPECT)/near infrared fluorescence (NIRF) imaging probe ^99mTc-PC-1007 is described. ^99mTc-PC-1007 exhibited preferential accumulation in human breast cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of ^99mTc-PC-1007 was performed in a breast cancer xenograft model. The probe uptake ratio of tumor to control (spinal cord) was calculated to be 4.02 ± 0.56 at 6 h post injection (pi) and 8.50 ± 1.41 at 20 h pi (P < 0.0001). Pharmacokinetic parameters such as blood clearance and organ distribution were assessed.     

First report of pulmonary large cell neuroendocrine carcinoma treated with stereotactic body radiation therapy

IntroductionPulmonary large-cell neuroendocrine carcinoma (LCNEC) is a very rare disease, comprising approximately 3% of lung cancers. Even for Stage I disease, recurrence after resection is common, with a poor five-year overall survival. We present the first report of stereotactic body radiotherapy (SBRT) for pulmonary LCNEC.MethodsA 54-year-old woman with a left upper lobe pulmonary nodule underwent a wedge resection with thoracoscopic mediastinal lymph node dissection, revealing a 2.3 cm pT1b N0 LCNEC. Approximately one year later, surveillance imaging demonstrated a new left upper lobe PET-avid nodule, resulting in completion left upper lobectomy revealing LCNEC, with 0/6 involved lymph nodes and negative staging studies. The patient subsequently chose surveillance over adjuvant chemotherapy; unfortunately 23 months later imaging revealed an enlarging 0.7 cm nodule adjacent to the previous resection site, despite the patient remaining in good health (KPS = 90). Subsequent restaging demonstrated no evidence of metastatic disease. Due to the morbidity of a third operation in this region, and based on the safety of SBRT for Stage I non small-cell lung cancer, the consensus decision from our thoracic oncology team was to proceed with SBRT as preferred management for presumptive second recurrence of LCNEC. The patient shortly thereafter underwent SBRT (50 Gy in 10 Gy/fraction) to this new nodule, 41 months following initial LCNEC diagnosis.ResultsFour months following SBRT, the patient remains in excellent clinical condition (KPS 90), with no evidence of disease spread on surveillance studies. The nodule itself demonstrated no evidence of growth following SBRT.ConclusionsThis first report of SBRT for pulmonary LCNEC demonstrates that SBRT is a feasible modality for this rare disease. A multidisciplinary thoracic oncology approach involving medical oncology, thoracic surgery, radiation oncology and pulmonology is strongly recommended to ensure proper patient selection for receipt of SBRT.     

Proteomic analysis of laser-microdissected paraffin-embedded tissues: (1) Stage-related protein candidates upon non-metastatic lung adenocarcinoma

We used formalin-fixed paraffin-embedded (FFPE) materials for biomarker discovery in cases of lung cancer using proteomic analysis. We conducted a retrospective global proteomic study in order to characterize protein expression reflecting clinical stages of individual patients with stage I lung adenocarcinoma without lymph node involvement (n = 7). In addition, we studied more advanced stage IIIA with spread to lymph nodes (n = 6), because the degree of lymph node involvement is the most important factor for staging. FFPE sections of cancerous lesions resected surgically from patients with well-characterized clinical history were subjected to laser microdissection (LMD) followed by Liquid Tissue? solubilization and digestion trypsin. Spectral counting was used to measure the amounts of proteins identified by shotgun liquid chromatography (LC)/tandem mass spectrometry (MS/MS). More than 500 proteins were identified from IA and IIIA cases, and non-parametric statistics showed that 81 proteins correlated significantly with stage IA or IIIA. A subset of those proteins were verified by multiple-reaction monitoring mass spectrometric quantitation (MRM assay), described in other paper in this issue. These results demonstrated the technical feasibility of a global proteomic study using clinically well documented FFPE sections, and its possible utility for detailed retrospective disease analyses in order to improve therapeutic strategy.     

Comparaison de l’IRM de diffusion et de la TEP/TDM au FDG dans le bilan des lymphomes

PurposeDiffusion weighted MRI (DW-MRI) sequences appear as a promising functional technique supplementary to morphologic MRI for oncology purposes. We evaluated the results of DW-MRI for the staging of lymphomas, compared to FDG PET/CT.MethodsTwenty-seven patients with lymphoma referred for FDG PET/CT (initial staging, relapse or treatment evaluation) were prospectively included. They underwent MRI including free breathing DW and T2 weighted imaging. Lymph node areas and organs involvement were listed for each modality and compared using Cohen's kappa (κ) test. MRI performances were evaluated using FDG PET as the gold standard. The results of PET and MRI were compared (with respect to the final staging by the haematologist).ResultsRegarding the lymph nodes, 154 involved areas were detected by MRI out of the 184 detected by PET, that is an excellent concordance (κ = 0.87), sensitivity of 0.84 and specificity of 1. Concordance and sensitivity were inferior for extranodal disease (notably bone lesions) with 27 lesions detected by MRI out of the 40 viewed with PET. Regarding pre-treatment evaluation, two patients were understaged both with PET and MRI (bone marrow involvement); assessment of stage was concordant for both modalities in 18 patients out of 21.ConclusionsPerformance of MRI including DW images was close to that of FDG PET/CT for lymph node areas involvement. Further studies are needed to assess its sensitivity for extranodal lesions, and its accuracy for determining the stage of the disease.     

Design and development of a dedicated portable gamma camera system for intra-operative imaging

PurposeWe developed a high performance portable gamma camera platform dedicated to identification of sentinel lymph nodes (SLNs) and radio-guided surgery for cancer patients. In this work, we present the performance characteristics of SURGEOSIGHT-I, the first version of this platform that can intra-operatively provide high-resolution images of the surveyed areas.MethodsAt the heart of this camera, there is a 43 × 43 array of pixelated sodium-activated cesium iodide (CsI(Na)) scintillation crystal with 1 × 1 mm² pixel size and 5 mm thickness coupled to a Hamamatsu H8500 flat-panel multi-anode (64 channels) photomultiplier tube. The probe is equipped with a hexagonal parallel-hole lead collimator with 1.2 mm holes. The detector, collimator, and the associated front-end electronics are encapsulated in a common housing referred to as head.ResultsOur results show a count rate of ∼41 kcps for 20% count loss. The extrinsic energy resolution was measured as 20.6% at 140 keV. The spatial resolution and the sensitivity of the system on the collimator surface was measured as 2.2 mm and 142 cps/MBq, respectively. In addition, the integral and differential uniformity, after uniformity correction, in useful field-of-view (UFOV) were measured 4.5% and 4.6%, respectively.ConclusionsThis system can be used for a number of clinical applications including SLN biopsy and radiopharmaceutical-guided surgery.     

Effet du traitement par pegfilgrastim sur la fixation de la fluorocholine (18F) par la moelle osseuse

This patient had been treated by radical prostatectomy for adenocarcinoma. Fifteen years later, he was referred to us due to occult biochemical recurrence (PSA = 1.56 ng/mL). Fluoride (18F) PET/CT and then fluorocholine (18F) (FCH) PET/CT were performed. On fluoride (18F) PET/CT, only one focus in the left iliac crest was suspicious but the biopsy of an osteoblastic anomaly had been performed 5 months before, with a negative result. On FCH PET/CT, a diffuse and intense uptake of bone marrow was noted, as well as a focus corresponding to a right external iliac lymph node, which had already been visualised on the previous FCH PET/CT and prompted endoscopic resection of three lymph nodes, which proved to be non-malignant. The osteomedullary uptake was attributed to a very recent treatment by pegfilgrastim, a recombinant human granulocyte colony stimulating factor (G-CSF). It was concluded that the recurrence was electively located in this lymphatic basin and IMRT was performed which led to a fourfold reduction in PSA serum levels. This observation illustrates the risk, never mentioned yet, of false-positive results concerning osteomedullary cancer spread, in case of treatment by G-CSF. It also confirms the role of FCH PET/CT in case of occult recurrence of prostate cancer, including verification of resection of a suspicious lymph node detected on a previous FCH PET/CT, and its capacity to guide IMRT.     

La tomographie par émission de positons au 2-[18F]fluoro-2-désoxy-d-glucose (TEP-FDG) permet d’identifier les stades A et B des leucémies lymphoïdes chroniques (LLC)

PurposeThere is no data in the literature concerning the utility of 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in chronic lymphocytic leukaemia (CLL), except for the diagnosis of Richter's transformations. The purpose of this study was to assess the potential role of FDG-PET in CLL stages A and B.Materials and methodsThirty-five patients (61 ± 9 years; 11 women, 24 men; 8B and 27A) have benefited of a FDG-PET scan at baseline, for example, before an eventual treatment. FDG-PET scans were analyzed visually and the maximum values of the Standardised Uptake Value (SUV_max) were measured in the main lymph nodes areas. The ability of FDG-PET to differentiate stages A and B patients was evaluated by Student's tests and Receiver Operating Characteristics (ROC) analysis.ResultsAll patients with a normal FDG-PET (n = 18) were stages A. The remaining 17 patients (9A and 8B) showed hypermetabolisms in nodal areas above (n = 17) and below (n = 9) the diaphragm, and no visceral involvement. The lymph nodes hypermetabolisms were always bilateral, and of low intensity (≤ mediastinum; 9A), or of higher intensity (≥ liver, 8B). The SUV_max of stage B (n = 8) were significantly higher than those of the 27 stages A, in all lymph nodes areas except in mediastinum. The highest intensity of FDG uptake was observed in axillary area in stages B patients (SUV_max = 2.74 ± 1.03). An axillary SUV_max of 1.33 is the most suitable value for the discrimination between stages A and B patients (ROC; AUC = 0.968; sensitivity 1.00; specificity 0.91).ConclusionLymph nodes hypermetabolisms are constant in the B stage, and more intense than in stage A. These anomalies are always bilateral, unlike what is observed in Richter's transformation. The intensity of axillary lymph nodes FDG uptake can distinguish CLL stages A and B.     

Phantom study quantifying the depth performance of a handheld magnetometer for sentinel lymph node biopsy

PurposeThe use of a magnetic nanoparticle tracer and handheld magnetometer for sentinel lymph node biopsy (SLNB) was recently introduced to overcome drawbacks associated with the use of radioisotope tracers. Unlike the gamma probe, the used magnetometers are not only sensitive to the tracer, but also the diamagnetic human body. This potentially limits the performance of the magnetometer when used clinically.MethodsA phantom, mimicking the magnetic and mechanical properties of the human axilla, was constructed. The depth performance of two current generation magnetometers was evaluated in this phantom. LN-phantoms with tracer uptake ranging from 5 to 500 μg iron were placed at clinically relevant depths of 2.5, 4 and 5.5 cm. Distance-response curves were obtained to quantify the depth performance of the probes.ResultsThe depth performance of both probes was limited. In the absence of diamagnetic material and forces on the probe (ideal conditions) a LN-phantom with high uptake (500 μg iron) could first be detected at 3.75 cm distance. In the phantom, only superficially placed LNs (2.5 cm) with high uptake (500 μg iron) could be detected from the surface. The penetration depth was insufficient to detect LNs with lower uptake, or which were located deeper.ConclusionThe detection distance of the current generation magnetometers is limited, and does not meet the demands formulated by the European Association for Nuclear Medicine for successful transcutaneous SLN localization. Future clinical trials should evaluate whether the limited depth sensitivity is of influence to the clinical outcome of the SLNB procedure.     

Dose to pelvic lymph nodes in image based high dose rate brachytherapy of carcinoma cervix

AimThe aim of this study is to analyse the dosimetry to the pelvic lymph nodes and its correlation to point B using CT based high dose rate brachytherapy of carcinoma cervix.BackgroundConventionally, dose to pelvic lymph nodes from intracavitary brachytherapy was reported by point B and by the reference points of the lymphatic trapezoid.Materials and methods30 consecutive CT based high dose rate applications were reviewed between February and March 2016. The high risk clinical target volume and the organs at risk and the pelvic nodal groups were contoured. DVH parameters for the right and left obturator nodal group, right and left external iliac nodal group and right and left internal iliac nodal group were recorded. Right and left point B doses were also recorded.ResultsOn analysis of the combined dose, it was found that all the DVH parameters were significantly different from point B, except the D100 obturator and D2cc internal iliac lymph node. There was a significant correlation between all DVH parameters and point B, except D2cc, D1cc and D0.1cc of external iliac. The obturator group received the highest dose contribution from brachytherapy. The mean D90 dose received per fraction for the obturator, external iliac and internal iliac nodes was 2.7 Gy, 1.17 Gy and 1.41 Gy, respectively.ConclusionsThere is a significant dose contribution to the pelvic lymph nodal groups during intracavitary brachytherapy. There is a low degree of correlation between point B dose and dosimetric parameters of the individual nodal groups. Hence, it is important to analyse the dose delivered to individual nodal groups during intracavitary brachytherapy, at least in patients with enlarged lymph nodes to calculate the cumulative dose delivered.     

A novel 18F-labeled pyridyl benzofuran derivative for imaging of β-amyloid plaques in Alzheimer’s brains

A potential probe for PET targeting β-amyloid plaques in Alzheimer’s disease (AD) brain, FPYBF-1 (5-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N,N-dimethylpyridin-2-amine), was synthesized and evaluated. In experiments in vitro, FPYBF-1 displayed high affinity for Aβ(1–42) aggregates (K_i = 0.9 nM), and substantial labeling of β-amyloid plaques in sections of postmortem AD brains but not control brains. In experiments in vivo, [¹⁸F]FPYBF-1 displayed good initial uptake (5.16%ID/g at 2 min postinjection) and rapid washout from the brain (2.44%ID/g at 60 min postinjection) in normal mice, and excellent binding to β-amyloid plaques in a murine model of AD. Furthermore, the specific labeling of plaques labeling was observed in autoradiographs of autopsied AD brain sections. [¹⁸F]FPYBF-1 may be a useful probe for imaging β-amyloid plaques in living brain tissue.     

Lymphocytic Thyroiditis is Associated with Increased Number of Benign Cervical Nodes and Fewer Central Neck Compartment Metastatic Lymph Nodes in Patients with Differentiated Thyroid Cancer

Objective: Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection.Methods: From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013.Results: Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT.Conclusion: Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear.Abbreviations:CCND = central compartment node dissectionDTC = differentiated thyroid cancerHT = Hashimoto thyroiditisLT = lymphocytic thyroiditisTgAb = thyroglobulin antibodyTPO = thyroid peroxidase     

Détermination par TEP-TDM au 18FDG du statut ganglionnaire dans les cancers du col utérin – intérêt de la mesure du SUV de la tumeur primitive

Purpose. – To evaluate the value of ¹⁸F-fluoro-2-désoxyglucose (FDG) PET-CT and maximal standardized uptake value (SUV_max) of the primary tumor for lymph node staging in cervical cancer.Materials and methods. – This retrospective study involved a series of 18 consecutive patients who had benefited from PET-CT and MRI at initial staging for a stage IB or higher cervical carcinoma. The SUV_max of each primary tumor was measured retrospectively. All patients had been previously treated by radiochemotherapy. Lymph node status was obtained in 12 of 18 cases.Results. – The sensitivity and specificity for determining lymph node status was 80 and 86%, respectively, for PET-CT, and 80 and 71% for MRI. In 16.6% of cases, PET-CT revealed unknown sus-diaphragmatic lesions. SUV_max of the primary tumor was significantly higher in the N+ than in the N− group (15.6 ± 1.6 vs 8.5 ± 3.9, p < 0.01). The optimal threshold was determined to be 10.8 from ROC analysis.Conclusion. – When staging with FDG PET-CT, SUV_max of a primary cervical cancer seems to be a good predictor of lymph node status. This could lead to an intensification of treatment for patients whose SUV_max is higher than 10.8. A prospective study would allow to assess a potential benefit of treatment intensification for patients with SUV_max higher than 10.8.     

Combined molecular MRI and immuno-spin-trapping for in vivo detection of free radicals in orthotopic mouse GL261 gliomas

Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T₁ relaxation, measured as %T₁ change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T₁ relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model.     

Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands

Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K_i = 5.5 ± 1.1 nM), was labeled with fluorine-18. [¹⁸F]-FTECMO displayed optimal lipophilicity (log D_pH7.4 = 1.6 ± 0.2) and high stability in rat and human plasma as well as sufficient stability in rat liver microsomes. In vitro autoradiography with [¹⁸F]-FTECMO revealed a heterogeneous and displaceable binding in mGluR5-rich brain regions. PET imaging with [¹⁸F]-FTECMO in Wistar rats, however, showed low brain uptake. Uptake of radioactivity into the skull was observed suggesting in vivo defluorination. Thus, although [¹⁸F]-FTECMO is an excellent ligand for the detection of mGluR5 in vitro, its in vivo characteristics are not optimal for the imaging of mGluR5 in rats in vivo.     

Intérêt de l’imagerie hybride TEMP-TDM pour la détection du ganglion sentinelle dans les cancers du sein

IntroductionSingle-Photon Emission Computed Tomography-Computed Tomography (SPECT-CT) is an hybrid technique which associates functional and morphological images. The aim of this study was to assess the role of SPECT-CT lymphoscintigraphy in sentinel node identification in patients with breast cancer.MethodsTwelve months prospective study was undertaken. Lymphoscintigraphy comprising planar and SPECT-CT acquisition was performed in 51 consecutive patients with breast cancer (mean age: 62 ± 11.3, range: 33–83 years). Planar and SPECT-CT images were interpreted separately and the two imaging techniques were compared with respect to their ability to identify sentinel node.ResultsAn add-value of SPECT-CT images was evidenced in 31% of cases: a more accurate anatomic localization in 21% of cases and identification of undeterminate sites of uptake in 10% of cases. Furthermore, SPECT-CT detected intramammary (4% of cases) and retromammary (2% of cases) sentinel nodes missed by planar imaging. SPECT-CT was more sensitive for internal mammary drainage detection (6% of cases). The added value proved higher in obese patients. Finally, functional and anatomical images fusion and three-dimensional overview provided clear and readily usable informations to the surgeon.ConclusionHybrid SPECT-CT imaging improves the preoperative localisation of sentinel nodes in patients with breast cancer, in particular in obese patients. SPECT-CT provides readily usable informations to the surgeon.     

Apport de la TEP/TDM au 18FDG dans la stadification initiale et l’évaluation précoce de la réponse thérapeutique des rhabdomyosarcomes pédiatriques

PurposeThe objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma.Patients and methodsPrior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years).ResultsPET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years).ConclusionThis study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment.