Measuring Distribution of An I-125 Labeled Elastin-Like Polypeptide (ELP) Nanoparticle Within Mice Tumors for Consideration as a Novel Technique of Delivering Brachytherapy
H Song1*, J Milligan1, K Lafata1, G Kelly1, A Chilkoti1, J Cai2, F Yin1, (1) Duke University, Durham, NC, (2) Hong Kong Polytechnic University, Hong Kong, China
Presentations
PO-GePV-M-210 (Sunday, 7/25/2021) [Eastern Time (GMT-4)]
Purpose: An elastin-like polypeptide (ELP) nanoparticle labeled with I-131 has been demonstrated to deliver curative radiation doses to xenografted tumors in mice. The ELP conjugate is soluble below body temperature and undergoes a thermally triggered phase transition to become an insoluble coacervate at body temperature, establishing a stable radioactive intratumoral depot. This work is to quantify activity distribution for the purpose of calculating radiation dose distribution.
Methods: Human pancreatic adenocarcinoma cells (BxPc3-luc2) were subcutaneously injected in 5 male nu/nu mice. When tumors grew to about 500 mm3, each mouse was injected with 300 uCi of ELP labeled with the X-ray emitter I-125 (instead of beta emitter I-131) for SPECT imaging. With ELP stabilized within tumor at 24 hours, the mice were sacrificed. The excised tumor was fixed in agarose in a plastic holder that was designed to allow for biopsy at two known locations. The tumor was then imaged with micro-SPECT/CT. After SPECT/CT imaging, small biopsy punches were taken. The absolute radioactivity of each biopsy sample was measured in a gamma counter and was used to convert the SPECT image intensity to absolute distribution of I-125 within the tumor.
Results: SPECT images show that ELP distribution within the tumor is inhomogeneous and an-isotropic. The intensity decays quickly with distance from the injection depot but not monotonously. Local hot spots were observed outside of the injection depot. For quantitative analysis, inconsistencies between SPECT intensity and radioactivity measured at the two biopsy points were observed, preventing reliable conversion of SPECT intensity to radioactivity.
Conclusion: If ELP intratumoral delivery is engineered for improved homogeneity within tumors, especially within larger tumors, ELPs have the potential to become a novel technique for delivering brachytherapy to the whole tumor volume. Inhomogeneous patterns of ELP diffusion in inhomogeneous tissue poses challenges to quantify its distribution.
Funding Support, Disclosures, and Conflict of Interest: Partially supported by NIH grant 1R21CA218940-01
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