The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Abstract

This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood-brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.

Keywords: CNS tumors; PET; central nervous system; drug development; molecular biology; molecular imaging; oncology; positron emission tomography; targeted therapy; theranostics.

Figure 1

Contrast-enhanced Magnetic Resonance Imaging (MRI) (top row) and multiple PET tracers for diagnostic imaging (bottom row) in glioblastoma. (a) [¹⁸F]-2-fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), (b) O-(2-[¹⁸F]-fluoroethyl)-L-tyrosine ([¹⁸F]FET), (c) [¹⁸F]Fluorocholine, (d) 1-(2-Nitro-imidazolyl)-3-[¹⁸F]fluoro-2-propanol ([¹⁸F]FMISO), (e) 3′-deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT). Adapted from [24]. This research was originally published in Glioblastoma [internet]. Bolcaen, J.; Acou, M.; Descamps, B.; Kersemans, K.; Deblaere, K.; Vanhove, C.; Goethals, I. PET for therapy response assessment in glioblastoma. In Glioblastoma [Internet]; De Vleeschouwer, S., Ed.; Codon Publications: Brisbane, AU, 2017.

Figure 2

Response of high-grade glioma to local therapy with a cumulated 2.2-GBq dose of [⁹⁰Y]Y-DOTA-TOC given in three cycles (from left to right: study before therapy, control study 3 months after second dose, control study 3 months after third dose, and control study 23 months after third dose). (A–F) T1-weighted enhanced MR images show diminishing contrast agent in tissue surrounding resection cavity throughout therapy. (A–J) [⁶⁸Ga]Ga-DOTA-TOC PET images representing somatostatin receptor status show increased tracer uptake around resection cavity before therapy (G) and normalization in control studies (A–J). Adapted from [103]. This research was originally published in JNM. Heute D, Kostron H, von Guggenberg E, Ingorokva S, Gabriel M, Dobrozemsky G, et al. Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC. J Nucl Med. 2010;51(3):397-400. © SNMMI.

Figure 3

MRI and PET-MRI fusion images of patients with diffuse midline glioma (DMG). (A–G) Top row: [⁸⁹Zr]Zr-bevacizumab PET (144 hrs post-injection) fused with T1-Gadolinium (Gd) weighted MRI per patient; middle row: T1-Gd weighted MRI; lower row: T2-weighted/Fluid-attenuated inversion recovery (FLAIR) MR-images. Five tumors show a variable uptake of [⁸⁹Zr]Zr-bevacizumab (white arrows), with both PET negative and positive areas within each tumor. Two primary tumors are completely PET negative (C and E), while the T2 weighted images show tumor infiltration in the whole pons of both patients. In the middle row, the red arrows represent the areas of contrast enhancement within the tumor. In four out of five primary tumors, the PET-positive area corresponds with the contrast-enhancing area on MRI of the tumors (A,B,F and G). In C, the tumor shows an MRI contrast-enhancing area, while there is no ⁸⁹Zr-bevacizumab uptake. Figure D shows a PET-positive tumor, while no Gd-enhancement is observed on MRI. Adapted from [137]. This research was originally published in JNM. Jansen MH, Veldhuijzen van Zanten SEM, van Vuurden DG, Huisman MC, Vugts DJ, Hoekstra OS, et al. Molecular Drug Imaging: (89)Zr-Bevacizumab PET in Children with Diffuse Intrinsic Pontine Glioma. J Nucl Med. 2017;58(5):711-6. © SNMMI.