Injectable Colloidal Gold for Use in Intrafractional 2D Image‐Guided Radiation Therapy

Abstract

In the western world, approximately 50% of all cancer patients receive radiotherapy alone or in combination with surgery or chemotherapy. Image-guided radiotherapy (IGRT) has in recent years been introduced to enhance precision of the delivery of radiation dose to tumor tissue. Fiducial markers are often inserted inside the tumor to improve IGRT precision and to enable monitoring of the tumor position during radiation therapy. In the present article, a liquid fi ducial tissue marker is presented, which can be injected into tumor tissue using thin and fl exible needles. The liquid fi ducial has high radioopacity, which allows for marker-based image guidance in 2D and 3D X-ray imaging during radiation therapy. This is achieved by surface-engineering gold nanoparticles to be highly compatible with a carbohydrate-based gelation matrix. The new fi ducial marker is investigated in mice where they are highly biocompatible and stable after implantation. To investigate the clinical potential, a study is conducted in a canine cancer patient with spontaneous developed solid tumor in which the marker is successfully injected and used to align and image-guide radiation treatment of the canine patient. It is concluded that the new fi ducial marker has highly interesting properties that warrant investigations in cancer patients.

Application of nanotechnology to cancer radiotherapy

“…It provided enhanced image contrast for both CT and 2D X-ray imaging and was not affected by the external irradiation. No side effects were found in neither the mice model nor the canine patient (Jolck et al 2015). In a mice model with intracerebral malignant gliomas, gold nanoparticles, 11 nm in size, were injected intravenously and IGRT was initiated by micro-CT.…”

“…Area of interest indicated with a red box . b – d Nanogel visualized from different angles (Jolck et al 2015) …”

Injectable iodine-125 labeled tissue marker for radioactive localization of non-palpable breast lesions

“…SAIB is generally-recognized-as-safe (GRAS) by the FDA and when diluted with ethanol (20% v/v), the viscosity is dramatically reduced (to 0.1 Pa·s [14]). This enables injection through hypodermic needles (≥27G) at ambient temperature [14][15][16][17]. Deposition in soft tissue results in ethanol efflux and the formation of a highly viscous, gel-like implant due to a non-solvent induced phase separation (NIPS) [14,17].…”

“…This enables injection through hypodermic needles (≥27G) at ambient temperature [14][15][16][17]. Deposition in soft tissue results in ethanol efflux and the formation of a highly viscous, gel-like implant due to a non-solvent induced phase separation (NIPS) [14,17]. SAIB formulations have among other applications been exploited recently in the development of radiopaque fiducial markers, as a matrix for hosting well-defined gold nanoparticles as well as a highly iodinated SAIB-derivative (BioXmark ® ) [17][18][19][20].…”

“…Deposition in soft tissue results in ethanol efflux and the formation of a highly viscous, gel-like implant due to a non-solvent induced phase separation (NIPS) [14,17]. SAIB formulations have among other applications been exploited recently in the development of radiopaque fiducial markers, as a matrix for hosting well-defined gold nanoparticles as well as a highly iodinated SAIB-derivative (BioXmark ® ) [17][18][19][20]. BioXmark ® was recently CE-marked and approved for clinical use as soft tissue marker for surgical procedures including radiotherapy in the EU.…”