First Human Trial of Src/Abl-Targeted PET Tumor Imaging with F-18 SKI-249380

Sloan-Kettering Inst Can Research, New York NY

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): 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.