In Vivo and Ex Vivo Sentinel Node Mapping Does Not Identify the Same Lymph Nodes in Colon Cancer

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.

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Highly Sensitive Identification of Lymphatic and Hematogenous Metastasis Routes of Novel Radiolabeled Exosomes Using Non-invasive PET Imaging

10.1101/2020.03.17.995860 ◽

2020 ◽

Author(s):

Kyung Oh Jung ◽

Young-Hwa Kim ◽

Seock-Jin Chung ◽

Keon Wook Kang ◽

Siyeon Rhee ◽

...

Keyword(s):

Lymph Nodes ◽

Optical Imaging ◽

Pet Imaging ◽

Ex Vivo ◽

The Body ◽

Hematogenous Metastasis ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Gamma Counter

Clinically, there has been significant interest in the use of exosomes for diagnostic applications as promising biomarkers and therapeutic applications as therapeutic vehicles. However, knowledge of in vivo physiological biodistribution of exosomes was difficult to assess until now. Physiological distribution of exosomes in the body must be elucidated for clinical application. In this study, we aimed to develop reliable and novel methods to monitor biodistribution of exosomes using in vivo PET and optical imaging.MethodsExosomes were isolated from cultured medium of 4T1, mouse breast cancer cells. Exosomes were labeled with Cy7 and 64Cu (or 68Ga). In mice, radio/fluorescent dye-labeled exosomes were injected through the lymphatic routes (footpad injection) and hematogenous metastatic routes (tail vein injection). Fluorescence and PET images were obtained and quantified. Radio-activity of ex vivo organs was measured by gamma counter.ResultsPET signals from exosomes in the lymphatic metastatic route were observed in the draining lymph nodes, which are not distinguishable with optical imaging. Immunohistochemistry revealed greater uptake of exosomes in brachial and axillary lymph nodes than inguinal lymph node. After administration through the hematogenous metastasis pathway, accumulation of exosomes was clearly observed in PET images in the lungs, liver, and spleen, showing results similar to ex vivo gamma counter data.ConclusionExosomes from tumor cells were successfully labeled with 64Cu (or 68Ga) and visualized by PET imaging. These results suggest that this cell type-independent, quick, and easy exosome labeling method using PET isotopes could provide valuable information for further application of exosomes in the clinic.

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A DROP-IN Beta Probe for Robot-Assisted 68Ga-PSMA Radioguided Surgery: First Ex Vivo Technology Evaluation Using Prostate Cancer Specimens

10.21203/rs.3.rs-36999/v1 ◽

2020 ◽

Author(s):

Francesco Collamati ◽

Matthias van OOsterom ◽

Micol De Simoni ◽

Riccardo Faccini ◽

Marta Fischetti ◽

...

Keyword(s):

Prostate Cancer ◽

Lymph Nodes ◽

Ex Vivo ◽

Gamma Probe ◽

Beta Particle ◽

Radioguided Surgery ◽

Robot Assisted ◽

Psma Pet ◽

Positive Lymph Nodes

Abstract Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET-isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET-tracers during robot-assisted tumor-receptor-targeted. In this study, we’ve engineered and validated the performance of a novel DROP-IN beta-particle (DROP-INb) detector.Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INb probe prototype, with merged a scintillating detector with a housing optimized for a 12 mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INb probe prototype was tested in a robotic setting. In the ex vivo setting, the probe – positioned by the robot- was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located <1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INb probe (S/B>3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INb detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

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