Handheld magnetic probe with permanent magnet and Hall sensor for identifying sentinel lymph nodes in breast cancer patients

Abstract The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers—without radioisotopes—in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities

Novel handheld magnetometer probe based on magnetic tunnelling junction sensors for intraoperative sentinel lymph node identification

Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required.A Cousins, G.L. Balalis, S.K. Thompson, D. Forero Morales, A. Mohtar, A.B. Wedding, B. Thierr

Core-shell semiconductor nanocrystals: Effect of composition, size, surface coatings on their optical properties, toxicity, and pharmacokinetics

Quantum dots are semiconducting nanocrystals that exhibit extraordinary optical properties. QD have shown higher photostability compared to standard organic dye type probes. Therefore, they have been heavily explored in the biomedical field. This review will discuss the different approaches to synthesis, solubilise and functionalise QD. Their main biomedical applications in imaging and photodynamic therapy will be highlighted. Finally, QD biodistribution profile and in vivo toxicity will be discussed

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

BACKGROUND: We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m ((99m)Tc) and indocyanine green (ICG). METHODS: We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with (99m)Tc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. RESULTS: Scintigraphic images showed increased accumulation of (99m)Tc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. CONCLUSION: Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients

Background Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. Methods This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. Results Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. Conclusions Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds