BibTex format
@article{Inglese:2026:10.1109/TRPMS.2026.3713623,
author = {Inglese, M and Islam, S and McLeavy, L and Mauri, F and Barwick, TM and Waldman, AD and O'Neill, K and Williams, M and Aboagye, EO and Toschi, N},
doi = {10.1109/TRPMS.2026.3713623},
journal = {IEEE Transactions on Radiation and Plasma Medical Sciences},
title = {Oligoclonal metabolic phenotypes of intracranial metastatic disease determined by unsupervised temporal clustering of FPIA PET data},
url = {http://dx.doi.org/10.1109/TRPMS.2026.3713623},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Intracranial metastatic disease (IMD) from diverse extracranial primaries can exhibit <sup>18</sup>F-fluoropivalate (FPIA)-detectable short-chain fatty acid transcellular flux, although substantial biological heterogeneity is expected across tumour types and lesions. However, regional metabolic variations within individual brain metastases have not been well characterized, especially given the challenges of obtaining spatially distinct biopsies in vivo. In this study, we applied an unsupervised time-series clustering approach to dynamic <sup>18</sup>F-fluoropivalate positron emission tomography data to interrogate intra-tumoural short-chain fatty acid transcellular flux heterogeneity. Three distinct metabolic subpopulations (here termed imaging-defined oligoclones - IDOs) were identified within treatment-naïve brain metastases (from lung, breast, melanoma, and colorectal primaries), each defined by a unique fluoropivalate uptake and retention kinetic profile. These clusters exhibited non-overlapping spatial distributions and showed distinct imaging phenotypes, as evidenced by divergent associations with overall survival and with the fluoropivalate net influx rate constant Ki. Notably, the metabolic IDOs were intermingled throughout lesions rather than confined to tumour core or periphery. In patients who underwent stereotactic radiosurgery and were rescanned 4–8 weeks later, we observed a remodeling of the metabolic clusters, including the loss of the rapid-uptake cluster post-treatment and a predominance of the slow-retention cluster, coincident with a uniform decrease in cellularity across all clusters. Our spatiotemporal clustering analysis identified intra-tumoural metabolic subpopulations in brain metastases with distinct kinetic behaviours and exploratory associations with outcome. These findings introduce a non-invasive imaging-based framework for characterizing metabolic heterogeneity in brain metastases and suggest that su
AU - Inglese,M
AU - Islam,S
AU - McLeavy,L
AU - Mauri,F
AU - Barwick,TM
AU - Waldman,AD
AU - O'Neill,K
AU - Williams,M
AU - Aboagye,EO
AU - Toschi,N
DO - 10.1109/TRPMS.2026.3713623
PY - 2026///
TI - Oligoclonal metabolic phenotypes of intracranial metastatic disease determined by unsupervised temporal clustering of FPIA PET data
T2 - IEEE Transactions on Radiation and Plasma Medical Sciences
UR - http://dx.doi.org/10.1109/TRPMS.2026.3713623
ER -