Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer

E E Verwer; C M L Zegers; W van Elmpt; R Wierts; A D Windhorst; F M Mottaghy; P Lambin; R Boellaard

doi:10.1186/s40658-016-0167-y

Pharmacokinetic modeling of a novel hypoxia PET tracer [¹⁸F]HX4 in patients with non-small cell lung cancer

EJNMMI Phys. 2016 Dec;3(1):30. doi: 10.1186/s40658-016-0167-y. Epub 2016 Dec 12.

Authors

E E Verwer^{1

2}, C M L Zegers³, W van Elmpt³, R Wierts⁴, A D Windhorst¹, F M Mottaghy^{4

5}, P Lambin³, R Boellaard^{6

7}

Affiliations

¹ Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
² Department of Nuclear Medicine & Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
³ Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
⁴ Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
⁵ Department of Nuclear Medicine, University Hospital RWTH Aachen, Aachen, Germany.
⁶ Department of Radiology & Nuclear Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. r.boellaard@vumc.nl.
⁷ Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands. r.boellaard@vumc.nl.

Abstract

Background: [¹⁸F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [¹⁸F]HX4 kinetics and assesses the performance of simplified methods for quantification of [¹⁸F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426 ± 72 MBq [¹⁸F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions.

Results: Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+V_B). Simplified measures correlated well with V_T estimates (tumor-to-blood ratio (TBr) R ² = 0.96, tumor-to-muscle ratio R ² = 0.94, standardized uptake value R ² = 0.89).

Conclusions: [¹⁸F]HX4 shows reversible kinetics in tumor tissue: 2T4k+V_B. TBr based on static imaging at 2 or 4 h can be used for quantification of [¹⁸F]HX4 uptake.

Keywords: 18F-3-Fluoro-2-(4-((2-Nitro-1H-Imidazol-1-yl)Methyl)-1H-1,2,3-Triazol-1-yl)Propan-1-ol ([18F]HX4); Hypoxia; Image-derived input function (IDIF); Molecular imaging; Non-small cell lung cancer (NSCLC); Positron emission tomography (PET); Standardized uptake value (SUV); Tracer kinetic modeling; Tumor-to-blood ratio.