Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

Sonja Schelhaas, Kathrin Heinzmann, Vikram R Bollineni, Gerbrand M Kramer, Yan Liu, John C Waterton, Eric O Aboagye, Anthony F Shields, Dmitry Soloviev, Andreas H Jacobs

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.

Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalTheranostics
Volume7
Issue number1
DOIs
Publication statusPublished - 2017

Cite this

Schelhaas, S., Heinzmann, K., Bollineni, V. R., Kramer, G. M., Liu, Y., Waterton, J. C., ... Jacobs, A. H. (2017). Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review. Theranostics, 7(1), 40-50. https://doi.org/10.7150/thno.16676
Schelhaas, Sonja ; Heinzmann, Kathrin ; Bollineni, Vikram R ; Kramer, Gerbrand M ; Liu, Yan ; Waterton, John C ; Aboagye, Eric O ; Shields, Anthony F ; Soloviev, Dmitry ; Jacobs, Andreas H. / Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review. In: Theranostics. 2017 ; Vol. 7, No. 1. pp. 40-50.
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Schelhaas, S, Heinzmann, K, Bollineni, VR, Kramer, GM, Liu, Y, Waterton, JC, Aboagye, EO, Shields, AF, Soloviev, D & Jacobs, AH 2017, 'Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review' Theranostics, vol. 7, no. 1, pp. 40-50. https://doi.org/10.7150/thno.16676

Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review. / Schelhaas, Sonja; Heinzmann, Kathrin; Bollineni, Vikram R; Kramer, Gerbrand M; Liu, Yan; Waterton, John C; Aboagye, Eric O; Shields, Anthony F; Soloviev, Dmitry; Jacobs, Andreas H.

In: Theranostics, Vol. 7, No. 1, 2017, p. 40-50.

Research output: Contribution to journalReview articleAcademicpeer-review

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T1 - Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

AU - Schelhaas, Sonja

AU - Heinzmann, Kathrin

AU - Bollineni, Vikram R

AU - Kramer, Gerbrand M

AU - Liu, Yan

AU - Waterton, John C

AU - Aboagye, Eric O

AU - Shields, Anthony F

AU - Soloviev, Dmitry

AU - Jacobs, Andreas H

PY - 2017

Y1 - 2017

N2 - The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.

AB - The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.

KW - Animals

KW - Dideoxynucleosides/administration & dosage

KW - Drug Evaluation, Preclinical

KW - Drug Monitoring/methods

KW - Neoplasms/diagnostic imaging

KW - Positron Emission Tomography Computed Tomography/methods

U2 - 10.7150/thno.16676

DO - 10.7150/thno.16676

M3 - Review article

VL - 7

SP - 40

EP - 50

JO - Theranostics

JF - Theranostics

SN - 1838-7640

IS - 1

ER -