Optimization of Sentinel Lymph Node Imaging Methodology Using Anionic Liposome and Hyaluronidase.
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ABSTRACT:
SUBMITTER: Sakurai Y
PROVIDER: S-EPMC8465215 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE:Radioscintigraphic imaging during sentinel lymph node (SLN) mapping could potentially improve localization; however, parallel-hole collimators have certain limitations. In this study, we explored the use of coded aperture (CA) collimators. PROCEDURES:Equations were derived for the six major dependent variables of CA collimators (i.e., masks) as a function of the ten major independent variables, and an optimized mask was fabricated. After validation, dual-modality CA and near-infrared (NIR) fluorescence SLN mapping were performed in pigs. RESULTS:Mask optimization required the judicious balance of competing dependent variables, resulting in sensitivity of 0.35%, XY resolution of 2.0 mm, and Z resolution of 4.2 mm at an 11.5-cm field of view. The findings in pigs suggested that NIR fluorescence imaging and CA radioscintigraphy could be complementary, but present difficult technical challenges. CONCLUSIONS:This study lays the foundation for using CA collimation for SLN mapping, and also exposes several problems that require further investigation.
| S-EPMC3156935 | biostudies-literature
Project description:BackgroundSentinel lymph node (SLN) procedure is now a widely accepted method of LN staging in selected invasive breast cancers (unifocal, size </= 2 cm, clinically N0, without previous treatment). Complete axillary clearance is no longer needed if the SLN is negative. However, the oncological safety of this procedure remains to be addressed in randomized clinical trials. One main pitfall is the failure to visualize SLN, resulting in incorrect tumor staging, leading to suboptimal treatment or axillary recurrence. Operative gamma cameras have therefore been developed to optimize the SLN visualization and the quality control of surgery.Case presentationA 44-year-old female patient with a 14-mm infiltrative ductal carcinoma underwent the SLN procedure. An operative gamma camera was used during and after the surgery. The conventional lymphoscintigraphy showed only one SLN, which was also detected by the operative gamma camera, then removed and measured (9.6 kBq). It was analyzed by frozen sections, showing no cancer cells. During this analysis, the exploration of the axillary area with the operative gamma camera enabled the identification of a second SLN with low activity (0.5 kBq) that conventional lymphoscintigraphy, surgical probe and blue staining had failed to visualize. Histological examination revealed a macrometastasis. Axillary clearance was then performed, followed by a postoperative image proving that no SLN remained. Therefore, the use of the operative gamma camera prevented an under-estimation of staging which would have resulted in a suboptimal treatment for this patient.ConclusionThis case report illustrates that an efficient operative gamma camera may be able to decrease the risk of false negative rate of the SLN procedure, and could be an additional tool to control the quality of the surgery.Trial registrationClinicalTrials.gov Identifier: NCT00357487.
| S-EPMC2203998 | biostudies-literature
Project description:Sentinel lymph node (SLN) mapping is a critical procedure for SLN biopsy and its diagnosis as tumor metastasis in clinical practice. However, SLN mapping agents used in the clinic frequently cause side effects and complications in the patients. Here, we report the development of a near-infrared (NIR) emitting polymeric nanogel with hydrodynamic diameter of ~28 nm - which is the optimal size for SLN uptake - for noninvasive fluorescence mapping of SLN in a mouse. This polymeric nanogel was obtained by coupling Cy7, an NIR dye, to the self-assembled nanogel from disulfide-linked dextran-deoxycholic acid conjugate with the dextran of 10 kDa, denoted as Dex-Cy7. Fluorescence imaging analysis showed that Dex-Cy7 nanogels had an enhanced photostability when compared to Cy7 alone. After intradermal injection of Dex-Cy7 nanogel into the front paw of a mouse, the nanogels were able to migrate into the mouse's axillary lymph node, exhibiting longer retention time and higher fluorescence intensity in the node when compared to Cy7 alone. An immunohistofluorescence assay revealed that the nanogels were localized in the central region of lymph node and that the uptake was largely by the macrophages. In vitro and in vivo toxicity results indicated that the dextran-based nanogels were of low cytotoxicity at a polymer concentration up to 1,000 μg/mL and harmless to normal liver and kidney organs in mice at an intravenous dose of 1.25 mg/kg. The results of this study suggest that NIR-emitting polymeric nanogels based on bioreducible dextran-deoxycholic acid conjugates show high potential as fluorescence nanoprobes for safe and noninvasive SLN mapping.
| S-EPMC4260688 | biostudies-literature
Project description: Not available
| S-EPMC8355834 | biostudies-literature
Project description:Purpose: Sentinel lymph node biopsy (SLNB) has emerged as the preferred standard procedure in patients with breast cancer, melanoma and other types of cancer. Herein, we developed a method to intra-operatively map SLNs and differentiate tumor metastases within SLNs at the same time, with the aim to provide more accurate and real-time intraoperative guidance. Experimental Design: Hyaluronic acid (HA), a ligand of lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, is employed as a SLN mapping agent after being conjugated with a near-infrared fluorophore (Cy5.5). Different sized HAs (5, 10 and 20K) were tested in normal mice and mice with localized inflammation to optimize LN retention time and signal to background ratio. Cetuximab, an antibody against epidermal growth factor receptor (EGFR), and trastuzumab, an antibody against human epidermal growth factor receptor 2 (HER2), were labeled with near-infrared fluorophore (IRDye800) for detecting metastatic tumors. LN metastasis model was developed by hock injection of firefly luciferase engineered human head neck squamous carcinoma cancer UM-SCC-22B cells or human ovarian cancer SKOV-3 cells. The metastases within LNs were confirmed by bioluminescence imaging (BLI). IRDye800-Antibodies were intravenously administered 24 h before local administration of Cy5.5-HA. Optical imaging was then performed to identify nodal metastases. Results: Binding of HA with LYVE-1 was confirmed by ELISA and fluorescence staining. HA with a size of 10K was chosen based on the favorable migration and retention profile. After sequential administration of IRDye800-antibodies intravenously and Cy5.5-HA locally to a mouse model with LN metastases and fluorescence optical imaging, partially metastasized LNs were successfully distinguished from un-metastasized LNs and fully tumor occupied LNs, based on the different signal patterns. Conclusions: Fluorophore conjugated HA is a potential lymphatic mapping agent for SLNB. Dual-tracer imaging with the combination of lymphatic mapping agents and tumor targeting agents can identify tumor metastases within SLNs, thus may provide accurate and real-time intra-operative guidance to spare the time spent waiting for a biopsy result.
| S-EPMC5196893 | biostudies-literature
Project description:ObjectivesNear-infrared fluorescence imaging has the potential to improve sentinel lymph node mapping in vulvar cancer, which was assessed in the current study. Furthermore, dose optimization of indocyanine green adsorbed to human serum albumin was performed.Study designNine vulvar cancer patients underwent the standard sentinel lymph node procedure using (99m)technetium-nancolloid and patent blue. In addition, intraoperative imaging was performed after peritumoral injection of 1.6 mL of 500, 750, or 1000 ?M of indocyanine green adsorbed to human serum albumin.ResultsNear-infrared fluorescence sentinel lymph node mapping was successful in all patients. A total of 14 sentinel lymph nodes (average, 1.6; range, 1-4) were detected: 14 radioactive (100%), 11 blue (79%), and 14 near-infrared fluorescent (100%).ConclusionThis study demonstrates feasibility and accuracy of sentinel lymph node mapping using indocyanine green adsorbed to human serum albumin. Considering safety, cost, and pharmacy preferences, an indocyanine green adsorbed to human serum albumin concentration of 500 ?M appears optimal for sentinel lymph node mapping in vulvar cancer.
| S-EPMC3246078 | biostudies-literature
Project description:SignificanceSentinel lymph node (SLN) biopsy is an important method for metastasis staging in, e.g., patients with malignant melanoma. Tools enabling prompt histopathological analysis are expected to facilitate diagnostics; optical technologies are explored for this purpose.AimThe objective of this exploratory study was to investigate the potential of adopting multiphoton laser scanning microscopy (MPM) together with fluorescence lifetime analysis (FLIM) for the examination of lymph node (LN) tissue ex vivo.ApproachFive LN tissue samples (three metastasis positive and two negative) were acquired from a biobank comprising tissues from melanoma patients. Tissues were deparaffinized and subjected to MPM-FLIM using an experimental MPM set-up equipped with a time correlated single photon counting module enabling FLIM.ResultsThe data confirm that morphological features similar to conventional histology were observed. In addition, FLIM analysis revealed elevated morphological contrast, particularly for discriminating between metastatic cells, lymphocytes, and erythrocytes.ConclusionsTaken together, the results from this investigation show promise for adopting MPM-FLIM in the context of SLN diagnostics and encourage further translational studies on fresh tissue samples.
| S-EPMC7070082 | biostudies-literature
Project description:PurposeTo determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection.Materials and methodsThe animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m (99mTc)-labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99mTc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99mTc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test.ResultsIn vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L±0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6×10(3) counts·sec(-1)·μW(-1) per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P=.005 to P=.042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation.ConclusionThe multireporter probe 99mTc-labeled Cy7 tilmanocept exhibits in vitro and in vivo receptor-binding properties for successful receptor-targeted SLN mapping with nuclear and optical imaging.
| S-EPMC3447170 | biostudies-literature
Project description:The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose.
| S-EPMC8508039 | biostudies-literature
Project description: Not available
| S-EPMC9978891 | biostudies-literature