Facilitated By

San Antonio Medical Foundation


UT Health San Antonio

The UT Health San Antonio, with missions of teaching, research and healing, is one of the country’s leading health sciences universities.

Principal Investigator(s)
Brenner, Andrew
Research Start Date

Glioblastoma (GBM) is the most common and most aggressive of the primary malignant brain tumor in adults,with a median overall survival of 19.6 months following multi-modality therapy. The main limiting factor indelivering a tumoricidal radiation dose is the toxicity to surrounding brain. Therapeutic radionuclides, due to ashort tissue path and differences in radiobiology, have the potential to extend the therapeutic window for radiationin GBM. However, a carrier is needed to deliver the isotope to the brain and maintain its localization at thedesired site, as otherwise they quickly disperse. Liposomal encapsulation has the potential to facilitateradioisotope retention within the tissue, but a method for the efficient loading of liposomes with the radioisotopeswas needed. This has been an essential limiting factor in the development of this technology, and has now beensuccessfully addressed. To overcome this, we have developed an encapsulation method using a customlipophilic molecule (BMEDA) that carries the rhenium radionuclides into the aqueous compartment of theliposome nanoparticles. The final investigational product is Rhenium nanoliposomes (186RNL).To characterize the retention, tolerability, and activity of 186RNL, we performed intratumoral infusions of 186RNLin rats bearing glioblastoma tumors. Increasing doses as high as 30-fold typical external beam doses consistentlyshowed that animals tolerated all doses without evidence of harm, and were associated with marked survivaldifferences. In addition, many of the rats had no residual tumor. A toxicity study was performed in beagles with186RNL or blank control nanoliposomes and produced no significant changes systemically or in the brains of dogsat 24 hours or 14 Days. In order to further characterize the drug product and address chemistry, manufacturing,and control concerns of FDA, we entered into a collaborative agreement with the NanotechnologyCharacterization Laboratory (NCL) of the National Cancer Institute (NCI). NCL was provided with manufacturingprotocols, reagents, and representative lots manufactured at the UTHSA. No significant difference was observedbetween RNL manufactured at the two sites and with marked stability of final product observed. The drug wascleared by the FDA to proceed to clinical study shortly thereafter. It is our specific hypothesis that 186RNL cansafely be administered to patients with recurrent progressive GBM at much higher radiation doses than can beachieved with current techniques, and that treatment with 186RNL will markedly improve survival in GBM patients.Continued clinical development is warranted. We therefore propose to test the maximum tolerable dose and safetyprofile of 186RNL in patients with recurrent glioma, determine the efficacy of 186RNL in recurrent glioblastoma, andto develop and validate a mathematical model to predict the distribution of 186RNL. The immediate goal of thisAim is to use early time point, patient-specific data, to calibrate a mechanism-based model, thereby allowing forthe accurate prediction of the distribution of 186RNL as a function of time. This model will be developed usingdata established in Aim 1, then used before delivery of 186RNL in the selection of the optimal point of injection inin Aim 2.

Collaborative Project
Clinical Care