Abstract
(4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a flourine-18 labeled glutamate analog that enables the noninvasive in vivo imaging of cellular redox status. [18F]FSPG is transported across the cell membrane by the cystine/glutamate antiporter, system xc−, whose expression is upregulated in multiple cancer types. The requirement of cystine for the biosynthesis of glutathione, a major antioxidant, connects [18F]FSPG tissue retention to the intracellular redox response via system xc− activity. We herein describe the use of [18F]FSPG positron emission tomography (PET) to image the tumor antioxidant response and highlight key methodological considerations.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Faubert B, Solmonson A, DeBerardinis RJ (2020) Metabolic reprogramming and cancer progression. Science 368(6487). https://doi.org/10.1126/science.aaw5473
Liu JY, Xia XJ, Huang P (2020) xCT: a critical molecule that links cancer metabolism to redox signaling. Mol Ther 28(11):2358–2366. https://doi.org/10.1016/j.ymthe.2020.08.021
Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, Sadato N, Yamamoto K, Okada K (2002) 11C-acetate PET imaging of prostate cancer. J Nucl Med 43(2):181–186
Qu W, Oya S, Lieberman BP, Ploessl K, Wang L, Wise DR, Divgi CR, Chodosh LA, Thompson CB, Kung HF (2012) Preparation and characterization of L-[5-11C]-glutamine for metabolic imaging of tumors. J Nucl Med 53(1):98–105. https://doi.org/10.2967/jnumed.111.093831
Farsad M, Schiavina R, Castellucci P, Nanni C, Corti B, Martorana G, Canini R, Grigioni W, Boschi S, Marengo M, Pettinato C, Salizzoni E, Monetti N, Franchi R, Fanti S (2005) Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis. J Nucl Med 46(10):1642–1649
Koglin N, Mueller A, Berndt M, Schmitt-Willich H, Toschi L, Stephens AW, Gekeler V, Friebe M, Dinkelborg LM (2011) Specific PET imaging of xC- transporter activity using a (1)(8)F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clin Cancer Res 17(18):6000–6011. https://doi.org/10.1158/1078-0432.CCR-11-0687
McCormick PN, Greenwood HE, Glaser M, Maddocks ODK, Gendron T, Sander K, Gowrishankar G, Hoehne A, Zhang T, Shuhendler AJ, Lewis DY, Berndt M, Koglin N, Lythgoe MF, Gambhir SS, Arstad E, Witney TH (2019) Assessment of tumor redox status through (S)-4-(3-[F-18] fluoropropyl)-L-glutamic acid PET imaging of system x(c)(-) activity. Cancer Res 79(4):853–863. https://doi.org/10.1158/0008-5472.Can-18-2634
Greenwood HE, McCormick PN, Gendron T, Glaser M, Pereira R, Maddocks ODK, Sander K, Zhang T, Koglin N, Lythgoe MF, Arstad E, Hochhauser D, Witney TH (2019) Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clin Cancer Res 25(8):2471–2482. https://doi.org/10.1158/1078-0432.CCR-18-3423
Park SY, Na SJ, Kumar M, Mosci C, Wardak M, Koglin N, Bullich S, Mueller A, Berndt M, Stephens AW, Cho YM, Ahn H, Chae SY, Kim HO, Moon DH, Gambhir SS, Mittra ES (2020) Clinical evaluation of (4S)-4-(3-[(18)F]Fluoropropyl)-L-glutamate ((18)F-FSPG) for PET/CT imaging in patients with newly diagnosed and recurrent prostate cancer. Clin Cancer Res 26(20):5380–5387. https://doi.org/10.1158/1078-0432.CCR-20-0644
Kavanaugh G, Williams J, Morris AS, Nickels ML, Walker R, Koglin N, Stephens AW, Washington MK, Geevarghese SK, Liu Q, Ayers D, Shyr Y, Manning HC (2016) Utility of [(18)F]FSPG PET to image hepatocellular carcinoma: first clinical evaluation in a US population. Mol Imaging Biol 18(6):924–934. https://doi.org/10.1007/s11307-016-1007-0
Magarik MA, Walker RC, Gilbert J, Manning HC, Massion PP (2018) Intracardiac metastases detected by 18F-FSPG PET/CT. Clin Nucl Med 43(1):28–30. https://doi.org/10.1097/RLU.0000000000001883
Mittra ES, Koglin N, Mosci C, Kumar M, Hoehne A, Keu KV, Iagaru AH, Mueller A, Berndt M, Bullich S, Friebe M, Schmitt-Willich H, Gekeler V, Fels LM, Bacher-Stier C, Moon DH, Chin FT, Stephens AW, Dinkelborg LM, Gambhir SS (2016) Pilot preclinical and clinical evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT imaging of intracranial malignancies. PLoS One 11(2):e0148628. https://doi.org/10.1371/journal.pone.0148628
Edwards R, Greenwood H, Witney T (2020) Robust and facile automated radiosynthesis of [18F]FSPG on the GE FASTlab. https://doi.org/10.26434/chemrxiv.13434143.v2
Witney TH, Lewis DY (2019) Imaging cancer metabolism with positron emission tomography (PET). Methods Mol Biol 1928:29–44. https://doi.org/10.1007/978-1-4939-9027-6_2
Greenwood HE, Nyitrai Z, Mocsai G, Hobor S, Witney TH (2020) High-throughput PET/CT imaging using a multiple-mouse imaging system. J Nucl Med 61(2):292–297. https://doi.org/10.2967/jnumed.119.228692
Gengenbacher N, Singhal M, Augustin HG (2017) Preclinical mouse solid tumour models: status quo, challenges and perspectives. Nat Rev Cancer 17(12):751–765. https://doi.org/10.1038/nrc.2017.92
Golubeva Y, Rogers K (2009) Collection and preparation of rodent tissue samples for histopathological and molecular studies in carcinogenesis. Methods Mol Biol 511:3–60. https://doi.org/10.1007/978-1-59745-447-6_1
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Timmermand, O.V., Witney, T.H. (2024). Imaging the Tumor Antioxidant Response with [18F]FSPG PET. In: Witney, T.H., Shuhendler, A.J. (eds) Positron Emission Tomography. Methods in Molecular Biology, vol 2729. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3499-8_14
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3499-8_14
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3498-1
Online ISBN: 978-1-0716-3499-8
eBook Packages: Springer Protocols