Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation

Bharathi Raja Rajaganapathy, Joseph J. Janicki, Peter Levanovich, Pradeep Tyagi, Jason Hafron, Michael B. Chancellor, Sarah Krueger, Brian Marples

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Purpose We primarily determined whether the small animal radiation research platform could create a rat radiation cystitis model via targeted bladder irradiation (phase I). The response to treating early phase radiation cystitis in rats with transurethral catheter instillation of liposomal tacrolimus was also examined (phase II). Materials and Methods In phase I 16 adult female Sprague Dawley® rats were used. Metabolic urination patterns were analyzed before and after exposure to 20, 30 or 40 Gy radiation. In phase II irradiated rats were randomly assigned to receive a single instillation of saline or liposomal tacrolimus. Results The 40 Gy radiation dose induced statistically significant reductions in the intermicturition interval compared to the lower radiation doses. By approximately 20 minutes 40 Gy radiation caused a significant decrease in the mean intermicturition interval (p <0.0001). Histological analysis revealed degenerative epithelial changes and urothelial swelling with evidence of pseudocarcinomatous epithelial hyperplasia. Therefore, 40 Gy were chosen for the phase II efficacy study. There was no measurable change in total voided urine volume after irradiation, or after liposomal tacrolimus or saline instillation. Liposomal tacrolimus significantly increased the post-irradiation intermicturition interval by approximately 30 minutes back to baseline (p <0.001). Conclusions The radiation cystitis rat model showed a dose dependent decrease in the intermicturition interval without inducing short-term skin or gastrointestinal damage. This study demonstrates that liposomal tacrolimus may be a promising new intravesical therapy for the rare, serious condition of radiation cystitis.

Original languageEnglish (US)
Pages (from-to)578-584
Number of pages7
JournalJournal of Urology
Volume194
Issue number2
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • abnormalities
  • animal
  • cystitis
  • models
  • radiation-induced
  • tacrolimus
  • urinary bladder

ASJC Scopus subject areas

  • Urology

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    Rajaganapathy, B. R., Janicki, J. J., Levanovich, P., Tyagi, P., Hafron, J., Chancellor, M. B., Krueger, S., & Marples, B. (2015). Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation. Journal of Urology, 194(2), 578-584. https://doi.org/10.1016/j.juro.2015.03.108