Development of a minimally invasive simultaneous estimation method for quantifying translocator protein binding with [18F]FEPPA positron emission tomography

Praveen Dassanayake; Udunna C Anazodo; Linshan Liu; Lucas Narciso; Maryssa Iacobelli; Justin Hicks; Pablo Rusjan; Elizabeth Finger; Keith St Lawrence

doi:10.1186/s13550-023-00950-1

Development of a minimally invasive simultaneous estimation method for quantifying translocator protein binding with [¹⁸F]FEPPA positron emission tomography

EJNMMI Res. 2023 Jan 12;13(1):1. doi: 10.1186/s13550-023-00950-1.

Authors

Praveen Dassanayake^{1

2}, Udunna C Anazodo^{3

4

5}, Linshan Liu⁴, Lucas Narciso^{3

4}, Maryssa Iacobelli⁴, Justin Hicks^{3

4}, Pablo Rusjan^{6

7}, Elizabeth Finger^{4

8}, Keith St Lawrence^{3

4}

Affiliations

¹ Department of Medical Biophysics, University of Western Ontario, London, ON, Canada. pdassana@uwo.ca.
² Lawson Health Research Institute, 268 Grosvenor St, London, ON, N6A 4V2, Canada. pdassana@uwo.ca.
³ Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.
⁴ Lawson Health Research Institute, 268 Grosvenor St, London, ON, N6A 4V2, Canada.
⁵ Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
⁶ Douglas Research Centre, Human Neuroscience Division, Montréal, QC, Canada.
⁷ Department of Psychiatry, McGill University, Montréal, QC, Canada.
⁸ Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.

Abstract

Background: The purpose of this study was to assess the feasibility of using a minimally invasive simultaneous estimation method (SIME) to quantify the binding of the 18-kDa translocator protein tracer [¹⁸F]FEPPA. Arterial sampling was avoided by extracting an image-derived input function (IDIF) that was metabolite-corrected using venous blood samples. The possibility of reducing scan duration to 90 min from the recommended 2-3 h was investigated by assuming a uniform non-displaceable distribution volume (V_ND) to simplify the SIME fitting.

Results: SIME was applied to retrospective data from healthy volunteers and was comprised of both high-affinity binders (HABs) and mixed-affinity binders (MABs). Estimates of global V_ND and regional total distribution volume (V_T) from SIME were not significantly different from values obtained using a two-tissue compartment model (2CTM). Regional V_T estimates were greater for HABs compared to MABs for both the 2TCM and SIME, while the SIME estimates had lower inter-subject variability (41 ± 17% reduction). Binding potential (BP_ND) values calculated from regional V_T and brain-wide V_ND estimates were also greater for HABs, and reducing the scan time from 120 to 90 min had no significant effect on BP_ND. The feasibility of using venous metabolite correction was evaluated in a large animal model involving a simultaneous collection of arterial and venous samples. Strong linear correlations were found between venous and arterial measurements of the blood-to-plasma ratio and the remaining [¹⁸F]FEPPA fraction. Lastly, estimates of BP_ND and the specific distribution volume (i.e., V_S = V_T - V_ND) from a separate group of healthy volunteers (90 min scan time, venous-scaled IDIFs) agreed with estimates from the retrospective data for both genotypes.

Conclusions: The results of this study demonstrate that accurate estimates of regional V_T, BP_ND and V_S can be obtained by applying SIME to [¹⁸F]FEPPA data. Furthermore, the application of SIME enabled the scan time to be reduced to 90 min, and the approach worked well with IDIFs that were scaled and metabolite-corrected using venous blood samples.

Keywords: Image-derived input function; Kinetic modeling; PET/MR; Positron emission tomography; Simultaneous estimation method; Translocator protein (TSPO) imaging.

Grants and funding

R3592A14/Alzheimer Society