Methods and systems for using therapeutic, diagnostic or prophylactic magnetic agents
Inventors
Shapiro, Benjamin • Emmert-Buck, Michael R.
Assignees
National Institutes of Health NIH • University of Maryland College Park • US Department of Health and Human Services
Publication Number
US-8579787-B2
Publication Date
2013-11-12
Expiration Date
2029-05-19
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Abstract
Systems and methods are disclosed for directing magnetizable particles comprising therapeutic agents to a target volume, or for guiding magnetizable particles comprising therapeutic agents from a first target volume to a second target volume, at a distance using a magnetic field, to enable the treatment of diseased areas including areas deep inside a patient's body. The methods may be used to diagnose or treat diseased areas within a patient, for example tumors of the lungs, intestines, and liver, and is also useful in enhancing the permeability of solid tumors to chemotherapeutic agents.
Core Innovation
The invention provides methods and systems for directing magnetizable particles carrying therapeutic, diagnostic, or prophylactic agents to a target volume within a patient or for moving such particles from a first target volume to a second target volume using externally applied shaped magnetic fields. This is intended to enable treatment of diseased areas, including tumors located deep within the patient's body, such as in the lungs, intestines, and liver, and to enhance the permeability of solid tumors to chemotherapeutic agents.
The problem addressed arises from the limitations of conventional cancer treatments, including surgery, radiation, chemotherapy, and immunotherapy, which have drawbacks such as inaccessibility of tumors, poor delivery of therapeutic agents to malignant tissue, drug resistance, non-specific toxicity, and inability to treat deep or multiple metastatic tumors effectively. Magnetic drug delivery approaches have been tried but fail to target tumors more than about 5 centimeters inside the body because the magnetic fields required would exceed safe levels, and they cannot stably confine magnetizable objects at a distance due to Earnshaw's Theorem.
The invention solves these problems by employing shaped magnetic fields that are controlled in space and time, using arrays of opposing magnets to overcome the limitations of static fields and enable containment and sweeping of magnetizable objects within desired target volumes, even deep inside the body. The methods include regional targeting, which confines particles to clinically relevant anatomical regions to treat multiple metastases simultaneously without requiring knowledge of exact tumor locations, and sweeping, which moves particles within or between target volumes to access poorly vascularized metastases. Feedback systems detect particle locations and dynamically adjust magnetic fields for precise control.
Claims Coverage
The patent claims cover methods for administering magnetizable particles to a patient and applying shaped dynamic magnetic fields formed by external opposing magnets to direct these particles to one or more target volumes within the patient. The claims include various configurations and applications of these methods.
Using shaped dynamic magnetic fields to focus or sweep magnetizable objects to target volumes within a patient
Methods comprising administering magnetizable objects to a patient and externally applying shaped, dynamic magnetic fields formed by external opposing magnets, changeable in time, to focus the particles to a first target volume or to sweep the particles through the first target volume.
Selection of target volumes associated with diseases and tumors
Target volumes can be selected to include cancers, vascular diseases, infections, or non-cancerous diseases, including primary tumors, metastatic tumors, infectious lesions or organisms, blood clots or diseased biological structures, and can encompass organs, organ systems, or specific anatomical regions.
Directing particles between multiple target volumes using magnetic and non-magnetic means
Methods comprising directing magnetizable objects to a first target volume and then to a second target volume, where at least one directing step uses shaped dynamic magnetic fields formed by external opposing magnets, and directing steps can use magnetic means, non-magnetic means (e.g., electrical, thermal, mechanical, chemical, biological), or combinations thereof.
Sweeping magnetizable objects between volumes to access poorly vascularized metastases
Methods for sweeping particles from a first target volume surrounding or linked to metastases into a second target volume containing poorly vascularized metastatic tumors, enabling treatment without precise knowledge of metastases’ location, size, or properties.
Using feedback control and detection for dynamic magnetic field application
Methods further comprising detecting the location of magnetizable objects within the patient and employing feedback controllers to dynamically control one or more externally applied magnetic fields in response to detection.
Magnetizable objects size ranges and labeling
Magnetizable objects having diameters from about 1 nm to 1 mm, comprising ferrofluid components, therapeutic, diagnostic or prophylactic agents, and detectable labels including radioisotopic, paramagnetic, CARS, fluorescence, microscopy, acoustic, impedance spectroscopy, or reflectance spectroscopy labels.
The claims collectively describe innovative methods for magnetically directing therapeutic or diagnostic magnetizable particles through timed and spatially shaped magnetic fields to specified target volumes within patients. These include focusing, sweeping between volumes, use of non-magnetic adjunct directing mechanisms, feedback control based on particle location sensing, and applications to various diseases and anatomical sites.
Stated Advantages
Ability to effectively treat the majority of clinically relevant metastatic tumors confined to specific anatomical regions.
Reducing systemic toxicity and side effects by sparing non-target tissues such as bone marrow and immune system.
Enabling simultaneous treatment of numerous tumors without needing precise tumor location information.
Accessing hard-to-reach metastatic tumors by sweeping magnetizable objects into poorly vascularized areas.
Permitting use of more highly toxic therapeutic agents safely due to better targeting.
Enhancing efficacy of short half-life therapeutic agents by concentrating them quickly at targets.
Reducing treatment expense by requiring smaller amounts of therapeutic agents overall.
Documented Applications
Treatment of cancer tumors including primary and metastatic tumors deep inside the body, such as in the lungs, intestines, and liver.
Diagnosis and treatment of diseases localized to specific anatomical regions, including infections and vascular diseases.
Enhancing permeability of solid tumors to chemotherapeutic agents.
Delivery of therapeutic, diagnostic or prophylactic agents to target volumes containing multiple metastatic tumors that may be undetectable by conventional diagnostic means.
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