Locally targeted delivery of a micron-size radiation therapy source using temperature-sensitive hydrogel.
OBJECTIVE
To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle.


METHODS
Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111.


RESULTS
RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively).


CONCLUSIONS
RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the kidneys. Preliminary data of RT-GEL as a delivery modality of a radiation source to a local tumor are promising.
Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa. Electronic address: yusung-kim@uiowa.edu.
Yusung
Y
Kim
Department of Orthopaedic Surgery, The University of Iowa, Iowa City, Iowa.
Dong Rim
DR
Seol
Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa.
Sucheta
S
Mohapatra
Department of Radiology, The University of Iowa, Iowa City, Iowa.
John J
JJ
Sunderland
Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa; Department of Radiology, The University of Iowa, Iowa City, Iowa.
Michael K
MK
Schultz
Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa; Department of Surgery, The University of Iowa, Iowa City, Iowa.
Frederick E
FE
Domann
Department of Biomedical Engineering, The University of Iowa, Iowa City, Iowa.
Tae-Hong
TH
Lim
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007205:Indium Radioisotopes / Q000737:chemistry; D007267:Injections; D008325:Mammary Neoplasms, Experimental / Q000532:radiotherapy*; D051379:Mice; D023421:Models, Animal; D009368:Neoplasm Transplantation; D011108:Polymers / Q000737:chemistry; D011312:Pressure; D011878:Radiotherapy / Q000295:instrumentation* / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D020100:Hydrogels; D007205:Indium Radioisotopes; D011108:Polymers