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Radiotherapeutic Platform

OVERVIEW

PLUS THERAPEUTICS plans to develop, manufacture, and commercialize nanoliposome-encapsulated BMEDA-chelated radioisotope drugs to treat various types of cancer. Our initial focus is on developing BMEDA-chelated Rhenium-186 NanoLiposome (186RNL) for the treatment of recurrent glioblastoma – a rare, incurable, and fatal disease.

Rhenium Radionuclide

Rhenium-186 (186Re) (half-life 90 hours) is a reactor produced isotope with great potential for medical therapy. It is in the same chemical family as Technetium-99m (99mTc), a radioactive tracer that is the most commonly used isotope for diagnostic scintigraphic imaging in nuclear medicine. Like 99mTc, rhenium is not taken up by bone and is readily cleared by the kidneys.

While 186Re emits therapeutic beta particles, every 10th isotope decay also produces a gamma photon. The average 186Re beta particle path length in tissue of 2 millimeters is ideal for treatment of solid tumors. Additionally, the emitted gamma photons have similar photon energy to those emitted by 99mTc, allowing for imaging of the isotope within the body on standard nuclear imaging equipment available in routine medical practice. Therefore, the 186Re isotope has great potential in Convection Enhanced Delivery (CED) applications of local therapy of solid tumors. However, a carrier is needed to deliver the isotope to the brain and maintain its localization at the desired site, as otherwise it would quickly disperse and be carried away from the site of injection by the circulatory system.

Rhenium, discovered in 1925, is a silvery-gray, heavy, transition metal and one of the rarest elements in the Earth’s crust.

NanoLiposomes

Nanotechnology describes the use of atoms, molecules, or compounds to create extremely small materials and structures, having a size of 100 to 1 nanometers, with special properties that can be applied across many disciplines including electronics, energy, environment, and medicine.  

In medicine, these materials and structures are often used for site-specific drug delivery and take the form various organic and inorganic nanoparticles.  Nanoparticle morphology, both size and shape, affects how cells in the body “see” these nanoparticles and ultimately influences their toxicity, distribution, and targeting ability.

Of the various nanotechnology drug delivery systems, NanoLiposomes have been extensively explored and undergone significant technical advances since they were first developed in 1965.  Today, many are regulatory-approved and clinically- and commercially-proven across multiple medical areas including, but not limited to, cancer treatment, fungal infections, and pain management.

NanoLiposomes are small, complex, spontaneously-forming drug carriers comprised of a precise formulation of naturally occurring phospholipids and cholesterol — nearly identiclal to the lipid membranes of normal human cells. This means that there are natural degradation pathways in the human body for these lipid nanoparticles.

NanoLiposome properties such as size and structure, electrical charge, lipid composition, and surface modification are each critical to the ability of the product to provide reproducible drug delivery required by regulatory authorities and relied upon by physicians and patients.  Although larger liposomes can be manufactured, the most useful size range for drug carrier applications is 80-100 nanometers.  NanoLiposomes of this size have the ability to facilitate retention at the site of injection.

186RNL (Rhenium-186 NanoLiposome)

NanoLiposomes in the 100 nanometer size range have been the most investigated carrier for convection-enhanced delivery (CED) of drugs  to the brain.  These studies include the use of CED-delivery of NanoLiposomes carrying chemotherapeutic agents directly to brain tumor, including drugs such as irinotecan and topotecan.  

If NanoLiposomes are to be utilized as a carrier for radioisotopes, a method for the efficient loading of NanoLiposomes with the radioisotopes is needed.  Such a method has been developed for the labeling of NanoLiposomes with radiotherapeutic Rhenium radionuclides to very high levels of specific activity.  This novel approach uses a specially developed molecule known as BMEDA-2 to chelate with Rhenium-186 and carry it into the interior of a NanoLiposome where it is irreversibly trapped.

What is 186RNL?

What interested us in 186RNL?

What makes 186RNL attractive?

PATENTS

PLUS THERAPEUTICS actively and continually assesses its patenting and enforcement strategy for new product candidates and technologies in both developed and emerging countries to ensure continued innovation and market access and to protect the investments made in research, development, manufacturing, and commercialization.  We also regularly perform systematic reviews of our existing patents to verify a patent’s therapeutic value and to evaluate if a patent should be abandoned or maintained.

Issued

TitleCountryPatent NumberFiling Date
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameUnited States7,718,1606/17/05
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameAustralia20032415985/22/03
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameCanada2,490,9595/22/03
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameFrance15368435/22/03
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameGermany60335469.65/22/03
Radiolabeled Compounds and Liposomes and Methods of Making and Using the SameUnited Kingdom15368435/22/03