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Review
. 2020 May 22;12(5):1322.
doi: 10.3390/cancers12051322.

Hypoxia PET Imaging with [18F]-HX4-A Promising Next-Generation Tracer

Sebastian Sanduleanu  1 , Alexander M A van der Wiel  1 , Relinde I Y Lieverse  1 , Damiënne Marcus  1 , Abdalla Ibrahim  1   2   3   4 , Sergey Primakov  1 , Guangyao Wu  1 , Jan Theys  1 , Ala Yaromina  1 , Ludwig J Dubois  1 , Philippe Lambin  1   2
Affiliations
Review

Hypoxia PET Imaging with [18F]-HX4-A Promising Next-Generation Tracer

Sebastian Sanduleanu et al. Cancers (Basel). .

Abstract

Hypoxia-a common feature of the majority of solid tumors-is a negative prognostic factor, as it is associated with invasion, metastasis and therapy resistance. To date, a variety of methods are available for the assessment of tumor hypoxia, including the use of positron emission tomography (PET). A plethora of hypoxia PET tracers, each with its own strengths and limitations, has been developed and successfully validated, thereby providing useful prognostic or predictive information. The current review focusses on [18F]-HX4, a promising next-generation hypoxia PET tracer. After a brief history of its development, we discuss and compare its characteristics with other hypoxia PET tracers and provide an update on its progression into the clinic. Lastly, we address the potential applications of assessing tumor hypoxia using [18F]-HX4, with a focus on improving patient-tailored therapies.

Keywords: [18F]-HX4; molecular imaging; positron emission tomography (PET); response assessment; theranostics; tumor hypoxia.

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Conflict of interest statement

The authors declare no actual or potential conflicts of interest. P.L. reports—within and outside the submitted work—grants or sponsored research agreements from Varian Medical, Oncoradiomics, ptTheragnostic/DNAmito, and Health Innovation Ventures. He received an advisor/presenter fee and/or reimbursements of travel costs/external grant writing fee and/or in-kind manpower contribution from Oncoradiomics, BHV, Merck, Varian, Elekta, ptTheragnostic, and Convert Pharmaceuticals. P.L. has shares in the company Oncoradiomics SA, Convert Pharmaceuticals, and The Medical Cloud Company SPRL, and is co-inventor of two issues patents with royalties on radiomics (PCT/NL2014/050248, PCT/NL2014/050728) licensed to Oncoradiomics, one issue patent on mtDNA (PCT/EP2014/059089) licensed to ptTheragnostic/DNAmito, three non-patented inventions (software) licensed to ptTheragnostic/DNAmito and Oncoradiomics and Health Innovation Ventures, and three non-issues, non-licensed patents on Deep Learning-Radiomics and LSRT (N2024482, N2024889, N2024889). S.S. reports a grant from NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek), during the conduct of the study.

Figures

Figure 1
Figure 1
The currently most-investigated 2-nitroimidazole PET tracers and their associated logP values.
Figure 2
Figure 2
History of hypoxia PET, with a focus on the third generation PET tracer 18F-HX4.
Figure 3
Figure 3
HX4 tracer accumulation in rats and patients. Units are provided in Becquerel/milliliter (Bq/mL) (a) Representative fused CT and PET image of a rhabdomyosarcoma R1 tumor-bearing rats 4 h after injection of [18F]-HX4. In this rat, tracer accumulation can be observed in the tumor and bladder, indicating selective tumor retention and renal excretion, respectively. Reproduced from Dubois et al., PNAS [6] (b) Representative fused CT and PET image of a head and neck cancer patient (NCT01504815 trial) 4 h after injection of [18F]-HX4 with defined primary gross tumor volume (blue) contour.
See this image and copyright information in PMC

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