PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice

The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications

HER1-Targeted 86Y-Panitumumab Possesses Superior Targeting Characteristics than 86Y-Cetuximab for PET Imaging of Human Malignant Mesothelioma Tumors Xenografts

Malignant mesothelioma (MM), a rare form of cancer is often associated with previous exposure to fibrous minerals, such as asbestos. Asbestos exposure increases HER1-activity and expression in pre-clinical models. Additionally, HER1 over-expression is observed in the majority of MM cases. In this study, the utility of HER1-targeted chimeric IgG(1), cetuximab, and a human IgG(2), panitumumab, radiolabeled with (86)Y, were evaluated for PET imaging to detect MM non-invasively in vivo, and to select an antibody candidate for radioimmunotherapy (RIT).Radioimmunoconjugates (RICs) of cetuximab and panitumumab were prepared by conjugation with CHX-A''-DTPA followed by radiolabeling with (86)Y. The HER1 expression of NCI-H226, NCI-H2052, NCI-H2452 and MSTO-211H human mesothelioma cells was characterized by flow cytometry. In vivo biodistribution, pharmacokinetic analysis, and PET imaging were performed in tumor bearing athymic mice.In vivo studies demonstrated high HER1 tumor uptake of both RICs. Significant reduction in tumor uptake was observed in mice co-injected with excess mAb (0.1 mg), demonstrating that uptake in the tumor was receptor specific. Significant differences were observed in the in vivo characteristics of the RICs. The blood clearance T(½)α of (86)Y-cetuximab (0.9-1.1 h) was faster than (86)Y-panitumumab (2.6-3.1 h). Also, the tumor area under the curve (AUC) to liver AUC ratios of (86)Y-panitumumab were 1.5 to 2.5 times greater than (86)Y-cetuximab as observed by the differences in PET tumor to background ratios, which could be critical when imaging orthotopic tumors and concerns regarding radiation doses to normal organs such as the liver.This study demonstrates the more favorable HER1-targeting characteristics of (86)Y-panitumumab than (86)Y-cetuximab for non-invasive assessment of the HER1 status of MM by PET imaging. Due to lower liver uptake, panitumumab based immunoconjugates may fare better in therapy than corresponding cetuximab based immunoconjugates

Rupture de l'anneau pelvien due à un traumatisme à basse énergie

Rupture de l'anneau pelvien due à un traumatisme à basse énergi

Is intraoperative opioids avoidance a utopia? A matched case-control study in laparoscopic hysterectomy.

peer reviewe

Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy.

BACKGROUND: Opioid-sparing strategies are recommended, and Opioid-Free Anaesthesia (OFA) is proposed in the literature. But few data exist about the feasibility of OFA in the routine practice. From a larger series of 21,463 patients receiving OFA, this work investigates the postoperative pain and related outcomes in patients undergoing laparoscopic hysterectomy. MATERIALS AND METHODS: This matched retrospective study concerned 521 patients scheduled for a laparoscopic hysterectomy between 2010 and 2015 (118 receiving OFA and 403 receiving anaesthesia with opioids, AO). Primary outcome was pain in the Post-Anaesthetic Care Unit (PACU). RESULTS: Among the 521 included patients, 403 received sufentanil (mean±SD: 0.1±0.05 mcg/kg), the only synthetic opioid used to balance anaesthesia. Concerning the 118 patients receiving OFA, most of them received an association of clonidine (97%) and ketamine (95%). Most of the patients in both groups received non-steroidal anti-inflammatory drugs. No difference in pain scores was observed between AO and OFA (median [IQR], respectively: 4 [0-5] vs. 4.5 [0-6], P=0.74). A difference in the perioperative morphine equivalent use was observed (mean±SD: 0.18±0.06 mg/kg vs. 0.09±0.06 mg/kg, P<0.001). No difference was observed regarding the nausea/vomiting incidences, use of anti-emetics, sedation scores, or time spent at the PACU. CONCLUSION: Coming from an extensive daily practice, these data show that OFA is feasible and not associated with higher pain scores or longer PACU stay, suggesting the absence of specific immediate complications

Evaluation of the impact of deep neuromuscular blockade on surgical conditions for laryngeal microsurgery with High Frequency Jet Ventilation. A comparison with no block during intravenous general anesthesia with topical lidocaine.

Laryngeal transoral surgery classically requires a neuromuscular block (NMB) to facilitate tracheal intubation and to improve surgical conditions. However, the short duration of most procedures and the potential complications of residual NMB lead to consider a no block approach. The hypothesis that intravenous anesthesia (remifentanil and propofol infusions) without NMB but including glottis topical lidocaine anesthesia would allow clinically acceptable laryngeal exposure and good surgical conditions was tested in the specific context of procedures undergone with High Frequency Jet Ventilation (HFJV). A prospective randomized clinical comparison. 66 consenting patients were planned to receive 0.6 mg·kg rocuronium or saline at random. The outcome measurements included the time and conditions to complete suspended laryngoscopy, and the surgical conditions rated by the surgeon. Any vocal cord movement or coughing was recorded. Data were compared using a Wilcoxon rank-sum test for numerical variables and chi-square test for categorical ones. Treatment failure was defined as an impossible laryngoscopy or a grade 4 surgical field occurring at any time during surgery and was compared to its null theoretical value by a general z-test. An interim analysis after completion of 50% patients was performed using Pocock boundaries at 0.0294 significance levels. A significant failure rate occurred in the non paralysed group (27%, p < 0.001). No coughing and no vocal cords movement occurred in the NMB group. Poorer surgical conditions were obtained without NMB (p = 0.011). Inducing a deep NMB ensured improved conditions during direct laryngeal microsurgery with HFJV