title: Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Bharathi Raja
authors.initials: BR
authors.lastname: Rajaganapathy
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Janicki
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Peter
authors.initials: P
authors.lastname: Levanovich
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jason
authors.initials: J
authors.lastname: Hafron
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: chancellormb@gmail.com.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sarah
authors.initials: S
authors.lastname: Krueger
authors.affiliation: Departments of Urology and Radiation Oncology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan; Lipella Pharmaceuticals, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Brian
authors.initials: B
authors.lastname: Marples
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D003556:Cystitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007322:Instillation, Drug; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D010386:Pelvic Neoplasms / Q000532:radiotherapy; D020011:Protective Agents; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000473:pathology / Q000528:radiation effects*; D019459:Urothelium / Q000473:pathology / Q000528:radiation effects
chemical_list: D007166:Immunosuppressive Agents; D020011:Protective Agents; D016559:Tacrolimus
keywords: abnormalities; animal; cystitis; models; radiation-induced; tacrolimus; urinary bladder
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