title: Noninvasive blood-free full quantification of positron emission tomography radioligand binding.
abstract: Full quantification of a positron emission tomography (PET) radioligand binding to its target is preferred because it requires the fewest assumptions, but generally involves measuring the concentration of free radioligand in the arterial plasma by collecting blood samples from the subject's radial artery during the scan, and performing metabolite analysis. This invasive, costly procedure deters subjects' participation, and requires specialized staff and equipment. Simultaneous estimation (SIME) can fully quantify binding using only PET data from multiple brain regions and one individual anchor value, which is based on a single arterial blood sample. Drawing this sample can still be challenging in clinical settings, particularly when using simultaneous PET/magnetic resonance scanners. Here we propose a methodology for full quantification of binding that does not require any blood samples. The methodology substitutes the SIME blood-based anchor with a value predicted using multiple linear regression of noninvasive, easy-to-collect variables related to the radioligand blood concentration, and individual metabolism, such as injected dose, body mass index, or body surface area. As a study case, we show here the methodology in comparison to analysis with full arterial-line blood sampling in a cohort of 23 available scans with [(11)C]CUMI-101, a partial agonist of the serotonin 5-HT1A receptors.
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute and Columbia University, New York, New York, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zanderigo
authors.affiliation: 1] Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York, USA [2] Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, New York, USA [3] Department of Biostatistics, Columbia University, Mailman School of Public Health, New York, New York, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: Department of Psychiatry and Radiology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D015992:Body Mass Index; D001830:Body Surface Area; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D016014:Linear Models; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011869:Radioligand Assay / Q000379:methods*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014227:Triazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: C529131:2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5-(2H,4H)-dione; D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D044263:Receptors, Serotonin, 5-HT1; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines