InCell-RT overcomes treatment resistance
and kills cancer cells without causing damage
to non-dividing healthy tissues
Central to InCell-RT technology is a nanometer-scale radiation source known as an Auger electron (EA) emission, which is derived from the radioisotope 125Iodine (125I). What makes EA emissions fundamentally different than other types of radiation used to treat cancer is the incredibly small range over which these emissions travel and have biologic effects (i.e., <10 nanometers). For perspective, the diameter of a DNA double helix is approximately 2 nanometers and the diameter of a typical cell is approximately 20,000 nanometers. Therefore, InCell-RT does not significantly damage cells until the 125I-derived EA emissions are localized to DNA.
Targeting of EA emissions to the DNA is accomplished by covalently attaching the 125I atom directly to uridine deoxyribonucleoside (125I-UDR) to create a molecule that is virtually identical to thymidine, one of the four fundamental components of DNA. Cells cannot distinguish between thymidine and the 125I-UDR radiotherapeutic compound, so they will take up 125I-UDR and incorporate it directly into their replicating DNA prior to cell division.
Incorporation of this "Trojan Horse" into the DNA localizes the EA emissions within range of the target, physically producing multiple, complex, double-stranded breaks in the double-helix that destroys the DNA.This DNA destruction is fundamentally different than the DNA damage caused by radiation therapy and chemotherapy, as it cannot be repaired by the cell’s DNA repair mechanisms. Therefore, DNA destruction irreversibly leads to cell death and treatment resistance cannot occur.
Organs and tissues in the body consist of highly specialized cells that typically do not undergo frequent cell division. Thus, cancer cells and the tumor-associated blood vessel cells are the predominant, if not exclusive, dividing cells in many LACs. When locally infused, 125I-UDR can selectively destroy these dividing cancer cells without causing significant damage to the underlying healthy tissue because DNA incorporation of 125I-UDR during cell division is required to kill cells. Local administration also minimizes the risk of undesirable effects to normal dividing cells outside of the treatment field (e.g., bone marrow, gastrointestinal tract, and mucosa), as 125I-UDR is metabolized and rapidly eliminated from the blood.
For certain LAC indications,125I-UDR can be administered via standard catheters. For other LAC indications, proprietary micro-catheter arrays are being developed to locally deliver 125I-UDR directly to cancer cells. These proprietary micro-catheter arrays are spatially deployed across tissues and provide convection-enhanced delivery (CED) of the 125I-UDR infusion fluid. CED is a process in which treatment fluid is infused directly into the interstitial space of tissue (i.e., the space between cells) at a rate that is high enough to overcome the innate ability of tissue to absorb extracellular fluid, but low enough to avoid excess fluid volume in the tissue (i.e., edema). Long-term, convection-enhanced delivery provides the optimal strategy to saturate large volumes of tumor-infiltrated tissue and ensures that all cancer cells within the treatment field undergo DNA replication in the presence of 125I-UDR.
LACs invade tissues adjacent to the original tumor
LACs respond poorly to conventional therapy
LACs often develop increased resistance to further therapy