Evaluating infusion methods and simplified quantification of synaptic density in vivo with [11C]UCB-J and [18F]SynVesT-1 PET

J Cereb Blood Flow Metab. 2023 Dec;43(12):2120-2129. doi: 10.1177/0271678X231200423. Epub 2023 Sep 5.

Abstract

For some positron emission tomography studies, radiotracer is administered as bolus plus continuous infusion (B/I) to achieve a state of equilibrium. This approach can reduce scanning time and simplify data analysis; however, the method must be validated and optimized for each tracer. This study aimed to validate a B/I method for in vivo quantification of synaptic density using radiotracers which target the synaptic vesicle glycoprotein 2 A: [11C]UCB-J and [18F]SynVesT-1. Observed mean standardized uptake values (SUV) in target tissue relative to that in plasma (CT/CP) or a reference tissue (SUVR-1) were calculated for 30-minute intervals across 120 or 150-minute dynamic scans and compared against one-tissue compartment (1TC) model estimates of volume of distribution (VT) and binding potential (BPND), respectively. We were unable to reliably achieve a state of equilibrium with [11C]UCB-J, and all 30-minute windows yielded overly large bias and/or variability for CT/CP and SUVR-1. With [18F]SynVesT-1, a 30-minute scan 90-120 minutes post-injection yielded CT/CP and SUVR-1 values that estimated their respective kinetic parameter with sufficient accuracy and precision (within 7±6%) . This B/I approach allows a clinically feasible scan at equilibrium with potentially better accuracy than a static scan SUVR following a bolus injection.

Keywords: Positron emission tomography (PET); bolus-infusion; equilibrium; modeling; synaptic vesicle protein 2 A (SV2A).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain / metabolism
  • Positron-Emission Tomography / methods
  • Pyridines / metabolism
  • Pyrrolidines*
  • Pyrrolidinones*
  • Radiopharmaceuticals / metabolism

Substances

  • SynVesT-1
  • Pyrrolidinones
  • Pyrrolidines
  • Pyridines
  • Radiopharmaceuticals