Microspheres for Liver Radiomicrospheres Therapy and Planning

Authors

Alejandro Amor-Coarasa, Florida International UniversityFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biomedical Engineering

First Advisor's Name

Anthony J. McGoron

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Joongho Moon

Third Advisor's Name

Wei-Chiang Lin

Fourth Advisor's Name

Yen-Chih Huang

Fifth Advisor's Name

Seza A. Gulec

Keywords

Liver, cancer, lung, perfusion, PET, SPECT, microspheres, 68Ga, radiomicrospheres, 99mTc, 90Y

Date of Defense

6-28-2013

Abstract

Liver cancer accounts for nearly 10% of all cancers in the US. Intrahepatic Arterial Radiomicrosphere Therapy (RMT), also known as Selective Internal Radiation Treatment (SIRT), is one of the evolving treatment modalities. Successful patient clinical outcomes require suitable treatment planning followed by delivery of the microspheres for therapy. The production and in vitro evaluation of various polymers (PGCD, CHS and CHSg) microspheres for a RMT and RMT planning are described. Microparticles with a 30±10 µm size distribution were prepared by emulsion method. The in vitro half-life of the particles was determined in PBS buffer and porcine plasma and their potential application (treatment or treatment planning) established. Further, the fast degrading microspheres (≤ 48 hours in vitro half-life) were labeled with ⁶⁸Ga and/or ^99mTc as they are suitable for the imaging component of treatment planning, which is the primary emphasis of this dissertation. Labeling kinetics demonstrated that ⁶⁸Ga-PGCD, ⁶⁸Ga-CHSg and ⁶⁸Ga-NOTA-CHSg can be labeled with more than 95% yield in 15 minutes; ^99mTc-PGCD and ^99mTc-CHSg can also be labeled with high yield within 15-30 minutes. In vitro stability after four hours was more than 90% in saline and PBS buffer for all of them. Experiments in reconstituted hemoglobin lysate were also performed. Two successful imaging (RMT planning) agents were found: ^99mTc-CHSg and ⁶⁸Ga-NOTA-CHSg. For the ^99mTc-PGCD a successful perfusion image was obtained after 10 minutes, however the in vivo degradation was very fast (half-life), releasing the ^99mTc from the lungs. Slow degrading CHS microparticles (> 21 days half-life) were modified with p-SCN-b-DOTA and labeled with ⁹⁰Y for production of ⁹⁰Y-DOTA-CHS. Radiochemical purity was evaluated in vitro and in vivo showing more than 90% stability after 72 and 24 hours respectively. All agents were compared to their respective gold standards (^99mTc-MAA for ⁶⁸Ga-NOTA-CHSg and ^99mTc-CHSg; ⁹⁰Y-SirTEX for ⁹⁰Y-DOTA-CHS) showing superior in vivo stability. RMT and RMT planning agents (Therapy, PET and SPECT imaging) were designed and successfully evaluated in vitro and in vivo.

Identifier

FI13080524

Recommended Citation

Amor-Coarasa, Alejandro, "Microspheres for Liver Radiomicrospheres Therapy and Planning" (2013). FIU Electronic Theses and Dissertations. 948.
https://digitalcommons.fiu.edu/etd/948