Injectable Biodegradable Multimodal Mammography Marker

Abstract

Introducing temporary markers for imaging studies is an idea, which in the proper clinical settings can be advantageous for patient compliance and in selected cases where a permanent marker is nondesirable. Hence, we developed injectable marker formulation using a biodegradable “pasty polymer” of poly­(ricinoleic acid-co-sebacic acid) (PSA:RA) containing iodixanol and iron oxide as contrast agents that can serve as a visual marker for the region suspected to have tumor growth. The goal of this work is to noninvasively evaluate the visibility, shape, and degradation of the injectable PSA:RA formulation using magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US). Prescreening of the marker formulation was performed under MRI and CT scanning using agar gel phantom models with poly­(l-lactide-co-ε-caprolactone) (PCL:LA) solid inserts (clips) that contained varying combinations of the contrast agents. The contrast agent combination with the PCL:LA clip that had the best visibility in both MRI and CT was selected and additionally tested as in PSA:RA formulation. Further, we evaluated the PSA:RA marker placement in bovine liver and poultry muscles. The PSA:RA formulation is predictable with good MRI, CT, and US visibility and shows no in vivo systemic toxicity symptoms when implanted subcutaneously in mice. Further, the advantage of PSA:RA formulation is its undefined shape and ease of injecting through a small gauge needle, making it possible to reach into the regions of the body.

Characterization and Evaluation of Injectable Biodegradable Polymer Multimodality Radiologic Markers in an In Vivo Murine Model

“…Each of the three polymers used in this study contained 20% Lipiodol and 0.2% w/w iron oxide based on prior studies documenting the adequate conspicuity of these concentrations on CT and MR, respectively. 10 The three polymer compounds were composed of Polymer A–PLGA 50:50, Polymer B–PLGA 75:25, and Polymer C–PCL. The polymers were formed into a rod shape of an adequate 1 mm diameter to fit into a biopsy syringe, similar to other commercially available markers used in clinical practice.…”

“… 9 Recently, a biodegradable implant has been designed and formulated incorporating clinically approved, commonly used contrast agents visible at both CT (computer tomography) and MR (magnetic resonance). 10 In a preliminary in vitro and a short-term in vivo study, the visibility, shape, and degradation of these biodegradable implants containing Lipiodol (an X-ray contrast medium) were evaluated by CT, and it was concluded that this Lipiodol-containing poly(ricinoleic acid- co -sebacic acid) polymer is visible on CT, enabling polymer degradation to be potentially monitored noninvasively. 10 Visualization of this material on both ultrasound and MR has been characterized for this product to determine the optimal polymer composition for conspicuity and biodegradability in vitro and ex vivo for up to 2 weeks.…”

“… 10 In a preliminary in vitro and a short-term in vivo study, the visibility, shape, and degradation of these biodegradable implants containing Lipiodol (an X-ray contrast medium) were evaluated by CT, and it was concluded that this Lipiodol-containing poly(ricinoleic acid- co -sebacic acid) polymer is visible on CT, enabling polymer degradation to be potentially monitored noninvasively. 10 Visualization of this material on both ultrasound and MR has been characterized for this product to determine the optimal polymer composition for conspicuity and biodegradability in vitro and ex vivo for up to 2 weeks. 10 It was further noted that alteration of the polymer formulation could affect the duration of visualization of these potentially degradable products.…”

“… 10 Visualization of this material on both ultrasound and MR has been characterized for this product to determine the optimal polymer composition for conspicuity and biodegradability in vitro and ex vivo for up to 2 weeks. 10 It was further noted that alteration of the polymer formulation could affect the duration of visualization of these potentially degradable products. Nevertheless, longer-term studies over a time frame of weeks to months needed for clinical markers have yet to be achieved.…”

“…One early example is a product that incorporates a water-soluble polyethylene glycol-based hydrogel polymer, which is readily identified by ultrasound detection but poorly visualized on other modalities . Recently, a biodegradable implant has been designed and formulated incorporating clinically approved, commonly used contrast agents visible at both CT (computer tomography) and MR (magnetic resonance) . In a preliminary in vitro and a short-term in vivo study, the visibility, shape, and degradation of these biodegradable implants containing Lipiodol (an X-ray contrast medium) were evaluated by CT, and it was concluded that this Lipiodol-containing poly­(ricinoleic acid- co -sebacic acid) polymer is visible on CT, enabling polymer degradation to be potentially monitored noninvasively .…”