Therapeutic—¹³¹I-MIP-1095
PSMA-targeted Systemic Radiotherapy:
Potential to Change the Outcome in the
Future Management of Prostate Cancer

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Radiation therapy is the medical use of ionizing radiation to treat cancer. There are two forms of radiation therapy: traditional radiotherapy, also known as external beam radiation, and targeted radiotherapy.

Traditional radiotherapy involves the use of focused external radiation beams that are aimed from several angles to intersect at the location of a tumor, providing a more concentrated dose of radiation at that site of disease than in the surrounding healthy tissue. Traditional radiation therapy is often used in combination with surgery, chemotherapy and/or hormone therapy. It is estimated that between 50-60% of cancer patients undergo radiation therapy during the course of their treatment. While effective for treating the primary tumor or local spread, external beam radiation may result in damage to the surrounding healthy tissue, and, importantly, is not appropriate when the cancer has metastasized to distant areas of the body.

The field of molecular medicine is facilitating the development of even more precise therapies through the creation of targeted radiotherapeutics. Molecular Insight is developing targeted therapeutic radiopharmaceuticals for the treatment of prostate cancer. These radiopharmaceuticals, administered systemically to a patient, consist of a homing portion of the molecule that seeks out and attaches to a cancer-restricted protein associated with the disease, enabling the delivery of the radioactive therapeutic portion of the molecule specifically to the diseased cancer cells thereby sparing the surrounding healthy tissue and organs. The ability to specifically deliver radiation to cancer cells anywhere in the body is a significant advance, allowing radiation to be applied to systemic disease.

Targeted therapeutic radiopharmaceuticals can be designed that are capable of delivering a variety of different radioisotopes—further enabling physicians to not only selectively target a tumor but to adjust the intensity of the radiation dose depending on the size and location of the tumor.

¹³¹I-MIP-1095 is Molecular Insight’s targeted radiotherapeutic under development for the treatment of metastatic prostate cancer. This compound is radiolabeled with the therapeutic radionuclide, iodine-131, a beta-particle-emitting radionuclide, capable of destroying tumor cells. Iodine-131 is the active therapeutic component in I-131-sodium iodide for thyroid cancer treatment and Bexxar™ for the treatment of lymphoma.

The anticancer effect of ¹³¹I-MIP-1095 relies on its ability to deliver lethal doses of radiation to prostate cancer cells. Administered by intravenous infusion it circulates throughout the body and localizes to prostate cancer metastases. ¹³¹I-MIP-1095 binds to the extracellular domain of prostate specific membrane antigen (PSMA), a protein that is amplified in >95% of prostate cancer cells. Upon binding PSMA, ¹³¹I-MIP-1095 is subsequently internalized by the prostate cancer cells. ¹³¹I-MIP-1095 is retained within the prostate cancer cell, allowing the intense energy emitted by iodine-131 to be absorbed in the tumor cells causing targeted cell death of prostate cancer. The ability to specifically deliver radiation to prostate cancer cells anywhere in the body is a significant advance, allowing this commonly used therapy (radiation) to be applied to systemic disease.

Preclinical data on this compound have shown high tumor uptake and a favorable tumor to kidney discrimination yielding a lethal radiation dose to the tumor while minimizing normal tissue dose. In human prostate cancer mouse models, ¹³¹I-MIP-1095, administered in single or multiple dose schedules, significantly reduced tumor burden for a prolonged period of time and enhanced survival with no significant signs of toxicity.

Molecular Insight expects to file an Investigational New Drug application for ¹³¹I-MIP-1095 by the end of 2012. The Company also plans to initiate a clinical study in early 2013 to determine the maximum tolerated dose and define dose-limiting toxicities, and to examine the pharmacokinetics, normal organ distribution, radiation dosimetry, and excretion of ¹³¹I-MIP-1095.