PET biomarkers and probes for treatment response assessment in glioblastoma: a work in progress
Several pharmacological approaches are used for glioblastoma (GBM) treatment, each hinging on the triggering of different biochemical or functional processes; the development of specific and sensitive PET procedures for monitoring their efficacy proceeds with the identification of such new treatments. This paper presents an overview of the available “tumour biomarker”–“PET probe” pairs (i.e. the combination of a tumour target and a selective PET radiopharmaceutical) for monitoring the different treatments for GBM tested in human subjects.
A bibliographic search for papers on PET imaging for assessing treatment response in GBM was performed in PubMed and Web of science databases using the following string: (PET or positron) and (glioblastoma) and (treatment) and (monitoring); papers dealing with studies in human subjects published over the last 10 years were reviewed. Further papers were extracted from the bibliography of the reviewed papers.
In this review, we highlight through a detailed table that in spite of the current use in GBM patients of a large variety of PET radiopharmaceuticals, very few papers have specifically addressed the issue of the optimization and use of imaging biomarker–probe pairs for the assessment of treatment response in GBM. While new PET probes are being developed for assessing old and new GBM biomarkers, very few clinical trials have been performed to this end.
Whereas it appears that the use of old and new PET radiopharmaceuticals can advance the non-invasive assessment of treatment response in GBM, the optimal match of biomarker–probe pairs although highly needed is still being sought in particular with the active development of new highly specific treatments characterized by novel antitumoral targeting strategies.
KeywordsBiomarkers Response assessment PET imaging Molecular targets Radiotracers
Dr. Salvatore was supported by a Fellowship from the Doctorate School in Molecular and Translational Medicine of University of Milan, Italy. This work was partly supported in part by FP7-funded INSERT project (HEALTH-2012- INNOVATION-1, GA305311). The authors specify that no commercial companies participated or contributed to manuscript preparation.
DS: literature search and writing. ALD: literature analysis, review and writing. CM: writing and review. CD: content planning and review. LO: content planning, review, editing, and final revision.
Compliance with ethical standards
Conflict of interest
The authors whose names are listed immediately below certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript: Daniela Salvatore, Alessia Lo Dico, Cristina Martelli, Cecilia Diceglie and Luisa Ottobrini
Statement on the welfare of animals/human
This article does not contain any new study with human or animal subjects performed by any of the authors. Only previously published results have been reported.
This article does not contain any new study with human participants or animals performed by any of the authors. Only previously published results have been reported.
- 5.Hattingen E, Pilatus U (2016) Brain tumor imaging. Springer, BerlinGoogle Scholar
- 14.Lohmann P, Lerche C, Bauer EK, Steger J, Stoffels G, Blau T, Dunkl V, Kocher M, Viswanathan S, Filss CP, Stegmayr C, Ruge MI, Neumaier B, Shah NJ, Fink GR, Langen KJ, Galldiks N (2018) Predicting IDH genotype in gliomas using FET PET radiomics. Sci Rep 8(1):13328. https://doi.org/10.1038/s41598-018-31806-7 (PMID: 30190592 Free PMC Article) Google Scholar
- 15.Papp L, Pötsch N, Grahovac M, Schmidbauer V, Woehrer A, Preusser M, Mitterhauser M, Kiesel B, Wadsak W, Beyer T, Hacker M, Traub-Weidinger T (2018) Glioma survival prediction with combined analysis of in vivo 11C-MET PET features, ex vivo features, and patient features by supervised machine learning. J Nucl Med 59(6):892–899. https://doi.org/10.2967/jnumed.117.202267 (Epub 2017 Nov 24 PMID: 29175980) Google Scholar
- 16.Lohmann P, Kocher M, Steger J, Galldiks N (2018) Radiomics derived from amino-acid PET and conventional MRI in patients with high-grade gliomas. Q J Nucl Med Mol Imaging 62(3):272–280Google Scholar
- 37.Mertens K, Acou M, Van Hauwe J, De Ruyck I, Van den Broecke C, Kalala JO, D’Asseler Y, Goethals I (2013) Less validation of 18F-FDG PET at conventional and delayed intervals for the discrimination of high-grade from low-grade gliomas: a stereotactic PET and MRI study. Clin Nucl Med 38(7):495–500Google Scholar
- 39.Kobayashi K, Ohnishi A, Promsuk J et al (2008) Enhanced tumor growth elicited by l-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery 62:493–504. https://doi.org/10.1227/01.neu.0000316018.51292.19 Google Scholar
- 44.Galldiks N, Dunkl V, Ceccon G, Tscherpel C, Stoffels G, Law I, Henriksen OM, Muhic A, Poulsen HS, Steger J, Bauer EK, Lohmann P, Schmidt M, Shah NJ, Fink GR, Langen KJ (2018) Early treatment response evaluation using FET PET compared to MRI in glioblastoma patients at first progression treated with bevacizumab plus lomustine. Eur J Nucl Med Mol Imaging 45(13):2377–2386. https://doi.org/10.1007/s00259-018-4082-4 (Epub 2018 Jul 7 PubMed PMID: 29982845) Google Scholar
- 47.Hutterer M, Nowosielski M, Putzer D, Waitz D, Tinkhauser G, Kostron H et al (2011) O-(2-18F-fluoroethyl)-l-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma. J Nucl Med Off Publ Soc Nucl Med 52:856–864. https://doi.org/10.2967/jnumed.110.086645 Google Scholar
- 48.Galldiks N, Rapp M, Stoffels G et al (2013) Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MR. Eur J Nucl Med Mol Imaging 40:22. https://doi.org/10.1007/s00259-012-2251. (Publisher Name Springer-Verlag Print ISSN1619-7070) Google Scholar
- 57.Jacobs AH, Thomas A, Kracht LW et al (2005) 18F-fluoro-l-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors. J Nucl Med 46:1948–1958Google Scholar
- 60.Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A, Turkheimer F, Hinz R (2013) [11C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging 40(9):1406–1419. https://doi.org/10.1007/s00259-013-2447-2 (PubMed PMID: 23715902; PubMed Central PMCID: PMC3738844) Google Scholar
- 70.Dercle L, Seban R-D, Lazarovici J et al (2018) 18 F-FDG PET and CT scans detect new imaging patterns of response and progression in patients with hodgkin lymphoma treated by anti-programmed death 1 immune checkpoint inhibitor. J Nucl Med 59:15–24. https://doi.org/10.2967/jnumed.117.193011 Google Scholar