Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer.

Previous studies have found that use of hexaminolevulinate (HAL) and blue light cystoscopy (BLC) during treatment of bladder cancer had a positive impact on overall survival after later cystectomy, indicating a potential treatment effect beyond improved diagnostic accuracy. The aim of our study was to determine whether HAL and BL mimicking clinically relevant doses in an orthotopic rat model could have therapeutic effect by inducing modulation of a tumor-specific immune response. We also assessed whether administration with a checkpoint inhibitor could potentiate any effects observed.

Novel high relaxivity colloidal particles based on the specific phase organisation of amphiphilic gadolinium chelates with cholesterol.

To obtain high T(1)-relaxivity colloidal particles with a simultaneously high loading of amphiphilic Gd-chelates, a novel drug dosage form based on the phase organisation of amphiphilic gadolinium chelates with cholesterol was developed. In order to find a formulation, which exhibit both high T(1)-relaxivity and gives small particles a D-optimal mixture design (experimental design) was applied. Gadolinium 1,4,7-tris(carboxymethyl)-10-(2-hydroxyhexadecyl)-1,4,7,10-tetraazacyclododecane (Gd-HHD-DO3A) and cholesterol at approximately equimolar ratio proved to form thermodynamic stable disc-like colloidal particles as seen by cryo-electron micrographs.

Liposomes as carriers of amphiphilic gadolinium chelates: the effect of membrane composition on incorporation efficacy and in vitro relaxivity.

The effects of membrane composition (phospholipid type and amount of cholesterol), liposome size, drug/lipid ratio (loading) and nature of the amphiphilic gadolinium (Gd) chelate on the incorporation efficacy and magnetic resonance (MR) contrast efficacy (longitudinal (T1) relaxivity) were investigated using a fractional factorial design. A highly lipophilic Gd-chelate was required to ensure complete liposome incorporation. High T1-relaxivity was obtained by using liposomes composed of cholesterol and phospholipids with short acyl chain lengths (dimyristoyl phosphatidyl choline (DMPC) and dimyristoyl phosphatidyl glycerol (DMPG).