Src/Abl tumor kinase inhibition has clinically-proven efficacy against common solid types of cancer after standard therapy has failed, benefitting a subgroup of patients - potentially millions of people worldwide. With a wave of new Src/Abl therapeutics in development, oncologists urgently need new Src/Abl -targeted assays that can tell them which patients will benefit;guide dosing strategy;and help them understand tumor response to Src/Abl therapy at the molecular level. If no suitable assays are found, Src/Abl solid tumor therapy may be abandoned for low overall response-rates, and the benefits to potentially millions of patients with progressive solid cancer who would have responded to Src/Abl -targeted therapy will be lost. The Investigators propose a new approach to Src/Abl diagnostics: a non-invasive scan that can evaluate how well a Src/Abl-targeted small molecule targets tumors inside patients. The Investigators predict that detection of Src/Abl tumor-targeting, through medical imaging, will predict which patients will benefit from Src/Abl-targeted therapy and provide new insights for planning how to prescribe Src/Abl-therapy. The Investigators have developed 18F-SKI-249380, a first-of-its-kind dasatinib-tracer, as a Src/Abl-targeted imaging agent for positron emission tomography (PET) scanning. The Investigators need to learn how the Src/Abl-targeted tracer behaves in humans, and the radiation dose it delivers, as a prerequisite to rational design of successful clinical trials with 18F-SKI-249380 PET. Solution: A first-in-human pilot trial, using microgram tracer-dose of 18F-SKI-249380, with minimal risk of patient toxicity, PET imaging and blood assays to obtain first-in-human data on dosimetry, metabolism, biodistribution, and excretion. The funding sought covers direct costs of the planned first in-human trial. The Investigators are a motivated team with distinguished qualifications for successful clinical development of dasatinib-tracer PET imaging: the inventor of 18F-SKI-249380;experienced attending staff in the Memorial Sloan Kettering Cancer Center (MSKCC) PET/Nuclear Medicine Service, Radiochemistry- Cyclotron Core, Medical Physics Department, and Oncology Services, including principal &co-investigators of MSKCC solid tumor trials with dasatinib and other Src/Abl therapeutics. The team's collective experience and longstanding collaborations offer a track-record of success in translational development of new PET tracers for oncologic imaging.
New cancer-fighting drugs, Src/Abl inhibitors, benefit a select subgroup of patients with common solid cancers, like lung, breast and prostate cancer, even after standard treatments fail;with a benefit rate that potentially means help to millions of peope worldwide. No available clinical tests can predict who will benefit or how Src/Abl inhibitors can best be prescribed, seriously hindering ongoing early phase solid- tumor therapy trials. To address this unmet clinical need, the Investigators are conducting the first in- human trial of a non-invasive positron emission tomography (PET) imaging study that evaluates how well Src/Abl inhibitors target tumors inside patients, which should provide oncologists urgently needed guidance in patient selection and dosing strategy in Src/Abl-targeted therapy.
| Dunphy, Mark P S; Harding, James J; Venneti, Sriram et al. (2018) In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine. Radiology 287:667-675 |
| Dunphy, Mark; Pandit-Taskar, Neeta; Fox, Josef J et al. (2017) The Precision of Hepatic Arterial Infusion Scintigraphy as a Quantitative Biomarker of Tumor Microvasculature. AJR Am J Roentgenol 209:182-186 |
