Theranostics 2020; 10(19):8677-8690. doi:10.7150/thno.47298 This issue Cite

Research Paper

Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline

Suraiya Dubash1, Marianna Inglese1, Francesco Mauri1, Kasia Kozlowski1, Pritesh Trivedi1, Mubarik Arshad1,2, Amarnath Challapalli1, Tara Barwick1,2, Adil Al-Nahhas2, Rex Stanbridge3, Conrad Lewanski3, Matthew Berry4, Frances Bowen4, Eric O. Aboagye1✉

1. Department of Surgery and Cancer, Imperial College London, United Kingdom.
2. Department of Radiology/Nuclear Medicine, Imperial College Healthcare NHS Trust, London, United Kingdom.
3. Department of Surgery and Cancer, Imperial College Healthcare NHS Trust, London, United Kingdom.
4. Department of Medicine and Integrated Care, Imperial College Healthcare NHS Trust, London, United Kingdom.

Citation:
Dubash S, Inglese M, Mauri F, Kozlowski K, Trivedi P, Arshad M, Challapalli A, Barwick T, Al-Nahhas A, Stanbridge R, Lewanski C, Berry M, Bowen F, Aboagye EO. Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline. Theranostics 2020; 10(19):8677-8690. doi:10.7150/thno.47298. https://www.thno.org/v10p8677.htm
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Abstract

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Purpose: The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited. We investigated such heterogeneity in Non-Small Cell Lung Cancer (NSCLC) with [18F]fluoromethyl-(1,2-2H4) choline ([18F]D4-FCH) and positron emission tomography/computed tomography (PET/CT).

Experimental design: [18F]D4-FCH (300.5±72.9MBq [147.60-363.6MBq]) was administered intravenously to 17 newly diagnosed NSCLC patients. PET/CT scans were acquired concurrently with radioactive blood sampling to permit mathematical modelling of blood-tissue transcellular rate constants. Comparisons were made with biopsy-derived choline kinase-α (CHKα) expression and diagnostic [18F]fluorodeoxyglucose ([18F]FDG) scans.

Results: Oxidation of [18F]D4-FCH to [18F]D4-fluorobetaine was suppressed (48.58±0.31% parent at 60 min) likely due to the deuterium isotope effect embodied within the design of the radiotracer. Early (5 min) and late (60 min) images showed specific uptake of tracer in all 51 lesions (tumors, lymph nodes and metastases) from 17 patients analyzed. [18F]D4-FCH-derived uptake (SUV60max) in index primary lesions (n=17) ranged between 2.87-10.13; lower than that of [18F]FDG PET [6.89-22.64]. Mathematical modelling demonstrated net irreversible uptake of [18F]D4-FCH at steady-state, and parametric mapping of the entire tumor showed large intratumorally heterogeneity in radiotracer retention, which is likely to have influenced correlations with biopsy-derived CHKα expression.

Conclusions: [18F]D4-FCH is detectable in NSCLC with large intratumorally heterogeneity, which could be exploited in the future for targeting localized therapy.

Keywords: [18F] Fluoromethyl-(1, 2-2H4)-choline, Positron Emission Tomography, heterogeneity choline metabolism, choline kinase alpha, lung cancer.


Citation styles

APA
Dubash, S., Inglese, M., Mauri, F., Kozlowski, K., Trivedi, P., Arshad, M., Challapalli, A., Barwick, T., Al-Nahhas, A., Stanbridge, R., Lewanski, C., Berry, M., Bowen, F., Aboagye, E.O. (2020). Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline. Theranostics, 10(19), 8677-8690. https://doi.org/10.7150/thno.47298.

ACS
Dubash, S.; Inglese, M.; Mauri, F.; Kozlowski, K.; Trivedi, P.; Arshad, M.; Challapalli, A.; Barwick, T.; Al-Nahhas, A.; Stanbridge, R.; Lewanski, C.; Berry, M.; Bowen, F.; Aboagye, E.O. Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline. Theranostics 2020, 10 (19), 8677-8690. DOI: 10.7150/thno.47298.

NLM
Dubash S, Inglese M, Mauri F, Kozlowski K, Trivedi P, Arshad M, Challapalli A, Barwick T, Al-Nahhas A, Stanbridge R, Lewanski C, Berry M, Bowen F, Aboagye EO. Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline. Theranostics 2020; 10(19):8677-8690. doi:10.7150/thno.47298. https://www.thno.org/v10p8677.htm

CSE
Dubash S, Inglese M, Mauri F, Kozlowski K, Trivedi P, Arshad M, Challapalli A, Barwick T, Al-Nahhas A, Stanbridge R, Lewanski C, Berry M, Bowen F, Aboagye EO. 2020. Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [18F]fluoromethyl-(1,2-2H4)-choline. Theranostics. 10(19):8677-8690.

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