Melanoma incidence is growing faster than any other cancer and the American Cancer Society reports that death rates for melanoma have been rising in the United States for the past 30 years. Alarmingly, melanoma is the most common cancer in young adults under 30. One characteristic of metastatic melanoma cells that is recognized as a potential target for new therapies is upregulation of cell surface melanocortin receptor subtype I (MCR1). However, there are no agents currently available that can be used to exploit this identifiable difference between melanoma cells and normal cells. This proposal is focused on development, validation and commercialization of novel class of theranostic [203/212Pb]-labeled peptides that bind with high affinity and specificity to MCR1 for targeted imaging and image-guided therapy of metastatic melanoma. Our innovative approach enlists matched-pair isotopes 203Pb/212Pb to enable unambiguous dosimetry based on 203Pb-SPECT imaging for 212Pb-alpha-particle therapy. Viewpoint Molecular Targeting, LLC has developed a strong business- partnership with Radiomedix that is driving our development and commercialization of diagnostic SPECT radiotracer, [203Pb]DOTA-VMT-MCR1, which will be followed by radiotherapeutic agent, [212Pb]DOTA-VMT- MCR1 in future R&D. Matched pair isotopes 203Pb/212Pb is also attractive due to a relatively long half-life (51 h) of 203Pb, which is favorable for centralized manufacturing of radiotracers for their direct shipment to imaging facilities and a 10 h half-life of 212Pb, which can be commercialized through regional therapy centers. Our overall objective is to develop effective theranostic approach for metastatic melanoma that improve diagnosis and therapy of melanoma and provide improved clinical outcomes with fewer-milder side effects than current therapies. To achieve these objectives, we propose the following specific aims: 1. Scale up and perform IND enabling validation preparations of [203Pb]DOTA-VMT-MCR1 for inclusion in an IND submission to the FDA for first in humans clinical imaging; and 2. Determine the feasibility of centralized manufacturing/distribution of [203Pb]DOTA-VMT-MCR1 for molecular imaging of metastatic melanoma.. Upon successful completion of our Aims, we expect to have validated a manufacturing process for production of ultra-high specific activity [203Pb]DOTA-VMT-MCR1 and to have collected required CMC data for submission of our clinical imaging IND. We further expect to have demonstrated the feasibility of centralized commercial manufacturing and distribution of [203Pb]DOTA-VMT-MCR1. These successes are expected to advance VMT-MCR1 through initial commercial risk-mitigating milestones to a first in humans clinical trial with [203Pb]DOTA-VMT-MCR1 for imaging melanoma of metastatic melanoma patients. These studies are the foundation to advance our [212Pb]DOTA-VMT-MCR1 therapy, which has the potential to circumvent drug resistance that limits the effectiveness of current treatments for metastatic melanoma.
This proposal is aimed to establish the feasibility of a novel radiolabeled 203Pb - labeled peptide conjugate for targeted imaging and future 212Pb-based image guided therapy of metastatic melanoma. No other agents are available that are based on this theranostic approach for metastatic melanoma cancer imaging and therapy.
| Li, Mengshi; Zhang, Xiuli; Quinn, Thomas P et al. (2017) Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer. Appl Radiat Isot 127:52-60 |
