Publications

BibTex format

@article{Dubash:2020:10.7150/thno.47298,
author = {Dubash, S and Inglese, M and Mauri, F and Kozlowski, K and Trivedi, P and Arshad, M and Challapalli, A and Barwick, T and Al-Nahhas, A and Stanbridge, R and Lewanski, C and Berry, M and Bowen, F and Aboagye, EO},
doi = {10.7150/thno.47298},
journal = {Theranostics},
pages = {8677--8690},
title = {Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [F-18]fluoromethyl-(1,2-H-2(4))-choline},
url = {http://dx.doi.org/10.7150/thno.47298},
volume = {10},
year = {2020}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Dubash,S
AU  - Inglese,M
AU  - Mauri,F
AU  - Kozlowski,K
AU  - Trivedi,P
AU  - Arshad,M
AU  - Challapalli,A
AU  - Barwick,T
AU  - Al-Nahhas,A
AU  - Stanbridge,R
AU  - Lewanski,C
AU  - Berry,M
AU  - Bowen,F
AU  - Aboagye,EO
DO  - 10.7150/thno.47298
EP  - 8690
PY  - 2020///
SN  - 1838-7640
SP  - 8677
TI  - Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [F-18]fluoromethyl-(1,2-H-2(4))-choline
T2  - Theranostics
UR  - http://dx.doi.org/10.7150/thno.47298
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000548566600003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.thno.org/v10p8677.htm
UR  - http://hdl.handle.net/10044/1/81446
VL  - 10
ER  -

Download

ProfessorEricAboagye

Contact

Assistant

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)