Molecular Insight Pharmaceuticals, Inc. Presents Human Data on Detection of Metastatic Prostate Cancer

The data will be highlighted at a scientific poster presentation on February 3, 2012 at the ASCO-2012 Genitourinary Cancers Symposium in San Francisco, CA. 99mTc-MIP-1404 and 99mTc-MIP-1405, internally developed at Molecular Insight, are technetium-99m-labeled small molecules that target prostate specific membrane antigen (PSMA), a protein expressed at high levels in primary and metastatic prostate cancer. The data demonstrated that 99mTc-MIP-1404 and 99mTc-MIP-1405 rapidly detected both bone and lymph node lesions in 6 metastatic prostate cancer patients and in some cases demonstrated a greater number of metastatic lesions in bone than bone scans, the standard of care for imaging skeletal metastases. Neither compound localized in the normal prostate gland, and both cleared from the blood rapidly, allowing rapid visualization of disease.

Study Background: PSMA is a well-established molecular target for developing radiopharmaceuticals for imaging and therapy of metastatic prostate cancers. 99mTc-MIP-1404 and 99mTc-MIP-1405 are small molecule inhibitors of PSMA that exhibit high affinity for the extracellular domain of this protein. Preclinical studies demonstrated that 99mTc-MIP-1404 and 99mTc-MIP-1405 bind to PSMA with high affinity and localize in tumors rapidly. This study, reporting the first human data obtained from images of six men with metastatic prostate cancer and also six healthy male subjects, was designed to assess the pharmacokinetics and tumor localizing characteristics of 99mTc-MIP-1404 and 99mTc-MIP-1405.

Study Results: Under an exploratory IND, using a cross-over design, the pharmacokinetics, and tumor imaging characteristics of 99mTc-MIP-1404 and 99mTc-MIP-1405 were compared in 6 healthy volunteers and 6 men with a history of prostate cancer and radiographic evidence of metastatic disease. Whole body images were obtained at 10 minute, 1, 2, 4 and 24-hour time intervals and demonstrated rapid and persistent uptake of both compounds in the salivary, lacrimal, and parotid glands. Liver and kidney uptake was also evident, with greater uptake and retention with 99mTc-MIP-1404. Both agents cleared the blood in a biphasic manner, with 99mTc-MIP-1404 demonstrating significantly lower urinary activity (7%) compared to 99mTc-MIP-1405 (26%). In men with metastatic prostate cancer, both compounds rapidly localized to lesions in lymph nodes and bone as early as 1 hour post injection. SPECT/CT images at 4 and 24 hours demonstrated excellent lesion contrast with target-to-background ratios up to 28:1. Good correlation was seen with bone scans in most patients, though, in general, more lesions were visualized with 99mTc-MIP-1404 and 99mTc-MIP-1405 than bone scan, the standard of care for imaging bone metastases.

Study Conclusions: 99mTc-MIP 1404 and 99m Tc-MIP 1405 rapidly detected soft tissue lesions in prostate cancer patients in both enlarged and sub-centimeter lymph nodes, and in some cases identified a greater number of skeletal lesions than bone scan. Since 99m Tc-MIP-1404 has minimal activity in the bladder, further work is planned to correlate imaging findings with histopathology in patients with newly diagnosed and metastatic prostate cancer.

Dr. John W. Babich, President and Chief Scientific Officer of Molecular Insight, noted, "99mTc-MIP-1404 represents a novel approach to SPECT-imaging of prostate cancer by directly imaging disease using a small molecule that specifically binds to the external domain of PSMA. When combined with commonly available SPECT imaging, 99mTc-MIP-1404 has the potential of replacing current detection methods -- bone scans, CT or MRI scans -- that can't provide the same level of detail when staging men with prostate cancer, following the progression of the disease, or monitoring response to treatment. 99mTc-MIP-1404 may also have the potential of aiding in the planning of radiation therapy through improved disease visualization and ensuring that normal tissues are spared the damage that can occur with the use of external beam radiotherapy. Molecular Insight plans to focus development to provide a more sophisticated means of decision-making for the urologist, radiation therapist, and medical oncologist and to facilitate better and improved long-term patient outcomes."