Biodegradable Fiducial Markers for Bimodal Near-Infrared Fluorescence- and X-ray-Based Imaging

Abstract

This study aimed to evaluate, for the first time, implantable, biodegradable fiducial markers (FMs), which were designed for bimodal, near-infrared fluorescence-based (NIRF) and X-ray-based imaging. The developed FMs had poly­(l-lactide-co-caprolactone)-based core–shell structures made of radiopaque (core) and fluorescent (shell) composites with a poly­(l-lactide-co-caprolactone) matrix. The approved for human use contrast agents were utilized as fillers. Indocyanine green was applied to the shell material, whereas in the core materials, iohexol and barium sulfate were compared. Moreover, the possibility of tailoring the stability of the properties of the core materials by the addition of hydroxyapatite (HAp) was examined. The performed in situ (porcine tissue) and in vivo experiment (rat model) confirmed that the developed FMs possessed pronounced contrasting properties in NIRF and X-ray imaging. The presence of HAp improved the radiopacity of FMs at the initial state. It was also proved that, in iohexol-containing FMs, the presence of HAp slightly decreased the stability of contrasting properties, while in BaSO4-containing ones, changes were less pronounced. A comprehensive material analysis explaining the differences in the stability of the contrasting properties was also presented. The tissue response around the FMs with composite cores was comparable to that of the FMs with a pristine polymeric core. The developed composite FMs did not cause serious adverse effects on the surrounding tissues even when irradiated in vivo. The developed FMs ensured good visibility for NIRF image-supported tumor surgery and the following X-ray image-guided radiotherapy. Moreover, this study replenishes a scanty report regarding similar biodegradable composite materials with a high potential for application.

Indocyanine green and iohexol loaded hydroxyapatite in poly(L‐lactide‐co‐caprolactone)‐based composite for bimodal near‐infrared fluorescence‐ and X‐ray‐based imaging

“…In this study, we proposed a novel composite for fiducial marker fabrication, which is compatible with both NIRF‐ and X‐ray‐based imaging which was compared with reference materials reported previously 11 . The composite, PHXG, is composed of 10 wt% of iohexol, 20 wt% of HAp in P[LAcoCL] matrix and a NIR dye, ICG, which content was tested in the range of 0.0001–0.01 wt%.…”

“…Apart from the ability to emit the fluorescence in the NIR range, the developed material absorbs the X‐ray radiation – it is radiopaque. In our recent work, 11 long‐term X‐ray‐based contrasting properties of PX and PXH composites were assessed in vitro and in vivo. We reported that in the presence of HAp, the release of iohexol was accelerated, which was determined indirectly by measuring changes in intensity of reconstructed images.…”

“…On the other hand, copolymers of L‐lactide and ‐caprolactone possess much higher elasticity than both homopolymers, which is favorable for soft tissue applications 22,23 . Moreover, poly(L‐lactide‐co‐caprolactone) (P[LAcoCL]) with a molar ratio of 70:30 have already been tested for FMs application due to its adequate mechanical properties and degradation profile 10,11,24 …”

“…These artifacts affect the treatment planning and calculation of dose distributions; whereas in case of polymer‐ based FMs these artifacts can be minimized 8,9 . Therefore, the newly developed FMs should have low stiffness, optimized radiopacity and be biodegradable to solve the aforementioned problems and avoid surgical intervention for the removal thereof 1,4,10,11 . Such properties may be provided by polymer‐based composite materials, which are gaining enormous interest due to the wide possibilities of adaptation of their functional properties.…”

Development of novel polymeric nanoagents and their potential in cancer diagnosis and therapy runing title: Polymeric nanoagents for cancer theranostics

“…Further, ICG@ PSMA nanoagents exhibit strong NIR fluorescence as well as reduced systemic toxicity for cervical cancer cells (Chen et al, 2021). Also, ICG can be encapsulated into other synthetic polymers to perform NIR imaging, including PLGA (Choi et al, 2021), polyethylene glycol (PEG) (Wang et al, 2022b), polymeric nanomicelles (PNMs) (Hsu et al, 2020), poly (allylamine hydrochloride) (PAH) (Bahmani et al, 2014), poly caprolactone (PCL) (Chien et al, 2018;Gorecka et al, 2022).…”