Assessing cancer treatment response using 18F-FSPG PET
Research type
Research Study
Full title
Improving response assessment in cancer by measurement of cellular redox status using 18F-FSPG positron emission tomography
IRAS ID
312860
Contact name
Gary Cook
Contact email
Sponsor organisation
King's College London
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Therapy resistance is one of the biggest challenges facing oncology. Despite a revolution in novel anti-cancer therapies, such as check-point inhibitors and proton beam therapy, durable responses are often not observed due to treatment resistance. A major challenge is the lack of accurate methods to early identification of patients who do not respond to standard-of-care therapy.
This project employs a novel radiotracer, 18F-FSPG, to allow early, non-invasive identification of tumours that fail to respond to standard-of-care treatments. 18F-FSPG is a radiolabelled glutamate analogue that is specifically transported into into cells via 'system xc−', which is over-expressed in multiple tumour types, where it provides the rate-limiting step for glutathione synthesis, the body’s primary antioxidant. Elevated system xc− activity and glutathione biosynthesis are causal factors in resistance to therapy.
In preclinical studies, tumour retention of 18F-FSPG is a sensitive marker of treatment resistance. Baseline scans in treatment-naïve mice accurately predicted therapeutic outcome, with approximately 3-fold high radiotracer uptake in those with chemotherapy-refractive disease. Furthermore, 18F-FSPG uptake reduces following treatment in drug-sensitivetumours. A decrease in 18F-FSPG preceded tumour shrinkage or glycolytic changes using 18F-FDG . Early human trials confirm high 18F-FSPG tumour-to-background images with no safety concerns.
Standard assessment of HNSCC response to chemoradiotherapy is determined through changes in tumour size and glycolytic activity by 18F-FDG PET/CT. However, response is not routinely assessed until 12 weeks after treatment, limiting the window of opportunity for intervention. Similarly, in patients with advanced NSCLC standard CT response assessment to immunotherapy +/- chemotherapy is performed at 9 weekly intervals but is insensitive for detecting response, and assessment is confounded by “pseudoprogression” when a responding tumour may initially increase in size before shrinking later.
We plan to trial 18F-FSPG in head and neck and lung cancer to see if it is a viable early marker of treatment efficacy.
REC name
London - Westminster Research Ethics Committee
REC reference
24/LO/0111
Date of REC Opinion
8 Apr 2024
REC opinion
Further Information Favourable Opinion