Hepatic tumor radioembolization in a rat model using radioactive rhenium (186Re/188Re) glass microspheres.
OBJECTIVE
The aim of this study was to fully characterize newly developed radioactive rhenium glass microspheres in vivo by determining their biodistribution, stability, antitumor effect, and toxicity after hepatic arterial injection in a syngeneic rat hepatoma model. The dose response of the tumors to increasing amounts of radioactive 186Re and 188Re microspheres was also determined.


METHODS
Rhenium glass microspheres were made radioactive by neutron activation and then injected into the hepatic artery of Sprague-Dawley rats containing 1-week-old Novikoff hepatomas. The biodistribution of the radioactivity and tumor growth were determined 1 h and 14 days after injection.


RESULTS
Examination of the biodistribution indicated a time-dependent, up to 7-fold increase in Novikoff hepatoma uptake as compared to healthy liver tissue uptake. After 14 days, the average T:L ratio was 1.97. Tumor growth in the rats receiving radioactive microspheres was significantly lower than in the group receiving nonradioactive microspheres (142% vs. 4824%, p = 0.048). Immediately after injection, 0.065% of the injected radioactivity was measured in the thyroid; it decreased to background levels within 24 h.


CONCLUSIONS
Radioactive rhenium microspheres are effective in diminishing tumor growth without altering hepatic enzyme levels. The microspheres are safe with respect to their radiation dose to healthy tissue and radiation release in vivo and can be directly imaged in the body with a gamma camera. Furthermore, rhenium microspheres have an advantage over pure beta-emitting microspheres in terms of preparation and neutron-activation time. In sum, this novel radiopharmaceutical may provide an innovative and cost-effective approach for the treatment of nonresectable liver cancer.
Häfeli
U O
UO
Department of Radiation Oncology, The Cleveland Clinic Foundation, OH 44195, USA.
Casillas
S
S
Dietz
D W
DW
Pauer
G J
GJ
Rybicki
L A
LA
Conzone
S D
SD
Day
D E
DE
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D004621:Embolization, Therapeutic / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008863:Microspheres; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium