AUTHOR=Salvi de Souza Giordana , Mossel Pascalle , Somsen Joost F. , Providência Laura , Bartels Anna L. , Willemsen Antoon T. M. , Dierckx Rudi A. J. O. , Furini Cristiane R. G. , Lammertsma Adriaan A. , Tsoumpas Charalampos , Luurtsema Gert 

TITLE=Evaluating image-derived input functions for cerebral [18F]MC225 PET studies

JOURNAL=Frontiers in Nuclear Medicine

VOLUME=Volume 5 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/nuclear-medicine/articles/10.3389/fnume.2025.1597902

DOI=10.3389/fnume.2025.1597902

ISSN=2673-8880

ABSTRACT=Kinetic modelling of brain PET data is crucial for estimating quantitative biological parameters, traditionally requiring arterial sampling. This study evaluated whether arterial samples could be omitted to estimate the image-derived input function (IDIF) using a long axial field-of-view PET scanner. The use of internal carotid arteries (ICA) for IDIF estimation, along with venous samples for plasma-to-whole blood ratios and plasma parent fractions, was also assessed. Six healthy volunteers underwent [18F]MC225 scans with manual arterial sampling. IDIFs were derived from the aortic arch (IDIFAA) and calibrated using manual arterial samples (IDIFAA_CAL). ICA-derived IDIF was also calibrated (IDIFCA_CAL) and compared to IDIFAA_CAL. In a separate group of six volunteers, venous and arterial samples were collected to evaluate plasma-to-whole blood ratios, plasma parent fractions, and IDIF calibration (IDIFCA_CAL_VEN). Volume of distribution (VT) of different brain regions was estimated for all IDIFs techniques, corrected for plasma-to-whole blood ratio and plasma parent fraction (IDIFAA,P, IDIFAA_CAL,P, IDIFICA_CAL,P and IDIFICA_CAL_VEN_P). Our findings revealed discrepancies between IDIFAA and arterial samples, highlighting the importance of calibration. The differences between IDIFAA,P and IDIFAA_CAL,P were 9.2% for area under the curve and 4.0% for brain VT. IDIFICA_CAL,P showed strong agreement with IDIFA_CAL,P, with 1.2% VT difference. Venous sampling showed consistent agreement with arterial sampling for plasma parameters but was unreliable for IDIF calibration, leading to 39% VT differences. This study emphasises that arterial samples are still required for IDIF calibration and reliable VT estimation for [18F]MC225 PET tracer. ICA-derived IDIF, when calibrated, provides reliable VT estimates. Venous sampling is a potential alternative for estimating plasma parameters, but it is unsuitable for IDIF calibration.Trial RegistryNCT05618119 (clinicaltrials.gov/study/NCT05618119).