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A Curable Composition and Method for Implantation

Modern radiotherapy delivery techniques can control both tumor infiltration and the bulky tumor by irradiating tumors with higher doses of radiation and greater spatial selectivity thus sparing surrounding normal tissues from radiation damage. In order to control tumor infiltration, the treatment beam needs to be accurately positioned with respect to the tumor. In recent years, image-guided radiotherapy (IGRT) has been integrated into the majority of radiotherapy treatment delivery machines.

Recent advancements in IGRT have allowed for the increase in radiation dose delivery to malignant tumors leading to better tumor control than ever before. However, the downside of dose escalation is the potential increase in toxicity to adjacent organs at risk. Due to the increase in IGRT treatments, various techniques have been explored to assist in tracking the location of tumors and surrounding critical structures. The most commonly used technique involves implantation of fiducial markers as surrogates of the target volumes with the linear accelerator built-in kilovoltage or megavoltage imaging systems. However, computed tomography (CT) images are limited in terms of detail and show only information about the bony anatomical structures. The use of MRI for the guidance of radiotherapy has revolutionized diagnostics imaging due to excellent soft tissue contrast.

Tissue characteristics can be imaged by determining the concentration of hydrogen (H1) protons within the tissue and weighting . Therefore, the MR image is an image of H1 protons. When tissues that contain hydrogen (i.e., protons) are subjected to a magnetic field, some of the proton nuclei spins align in the same direction as the magnetic field. The MR-Linac (MRL) combines two advanced technologies to precisely locate tumors in real-time, and adapt the shape of the X-ray beams in real time to conform to the shape of the tumor.  However, the location of tumors, as well as normal tissues and organs at risk inside the body, change frequently. Therefore, there is still a risk of the tumor shifting location, which increases the probability of delivering unnecessary radiation dose to adjacent healthy tissues or organs.

Precise adaptive radiotherapy guided by real-time MRI images could prove a significant advance in radiation oncology in general if the daily location of tumors and its proximity to surrounding critical structures can be accurately determined. To overcome this challenge, a minimally invasive MRI-visible marker system would significantly improve the efficiency of MRI-guided radiotherapy. Therefore, a key requirement for an MRI-visible marker system is to have a different MRI signal intensity to that of normal tissues. This will enable the markers to be clearly distinguished from normal tissues and also, enable them to be used for tumor tracking and daily pre-treatment quality assurance procedures.

In view of the forgoing, this invention is developed to provide a biocompatible curable composition which includes metallic nanoparticles and is cured in situ upon contact with moisture to provide a fiducial marker which is visible by an imaging modality and useful in radiation therapy.

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