NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies

Alexander M. Spence; Mark Muzi; Jeanne M. Link; Finbarr O'Sullivan; Janet F. Eary; John M. Hoffman; Lalitha K. Shankar; Kenneth A. Krohn

doi:10.1007/s11307-009-0215-2

NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[¹⁸F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies

Alexander M. Spence, Mark Muzi, Jeanne M. Link, Finbarr O'Sullivan, Janet F. Eary, John M. Hoffman, Lalitha K. Shankar, Kenneth A. Krohn

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Purpose: 3′-Deoxy-3′-[¹⁸F]fluorothymidine ([¹⁸F]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-d-glucose (FDG). Procedures: Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [¹⁸F]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (K_FLT), blood to tissue transport (K₁), and phosphorylation (k₃). FDG-PET scans were obtained 75-90 min postinjection. Results: K_FLT and k₃, but not K₁ or k₃/k₂+k₃, reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance. Conclusions: K_FLT (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer.

Original language	English (US)
Pages (from-to)	343-355
Number of pages	13
Journal	Molecular Imaging and Biology
Volume	11
Issue number	5
DOIs	https://doi.org/10.1007/s11307-009-0215-2
State	Published - 2009
Externally published	Yes

Keywords

3′-[F]fluoro-3′-deoxythymidine
FLT
Fluorothymidine
Glioma
Positron emission tomography (PET)
Proliferation imaging
Radionecrosis

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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Spence, A. M., Muzi, M., Link, J. M., O'Sullivan, F., Eary, J. F., Hoffman, J. M., Shankar, L. K., & Krohn, K. A. (2009). NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[¹⁸F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies. Molecular Imaging and Biology, 11(5), 343-355. https://doi.org/10.1007/s11307-009-0215-2

NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[¹⁸F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies. / Spence, Alexander M.; Muzi, Mark; Link, Jeanne M. et al.
In: Molecular Imaging and Biology, Vol. 11, No. 5, 2009, p. 343-355.

Research output: Contribution to journal › Article › peer-review

Spence, AM, Muzi, M, Link, JM, O'Sullivan, F, Eary, JF, Hoffman, JM, Shankar, LK & Krohn, KA 2009, 'NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[¹⁸F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies', Molecular Imaging and Biology, vol. 11, no. 5, pp. 343-355. https://doi.org/10.1007/s11307-009-0215-2

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title = "NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: Preliminary efficacy studies",

abstract = "Purpose: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-d-glucose (FDG). Procedures: Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [18F]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (KFLT), blood to tissue transport (K1), and phosphorylation (k3). FDG-PET scans were obtained 75-90 min postinjection. Results: KFLT and k3, but not K1 or k3/k2+k3, reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance. Conclusions: KFLT (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer.",

keywords = "3′-[F]fluoro-3′-deoxythymidine, FLT, Fluorothymidine, Glioma, Positron emission tomography (PET), Proliferation imaging, Radionecrosis",

author = "Spence, {Alexander M.} and Mark Muzi and Link, {Jeanne M.} and Finbarr O'Sullivan and Eary, {Janet F.} and Hoffman, {John M.} and Shankar, {Lalitha K.} and Krohn, {Kenneth A.}",

note = "Funding Information: Acknowledgments. Pam Pham, Michele F. Wanner, Jeffrey Scharnhorst, and Neha Patel are gratefully acknowledged for their indispensable help. Supported by National Cancer Institute Contract N01-CM-37008 and NIH grants CA42045 and S10 RR17229.",

year = "2009",

doi = "10.1007/s11307-009-0215-2",

language = "English (US)",

volume = "11",

pages = "343--355",

journal = "Molecular Imaging and Biology",

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T1 - NCI-Sponsored trial for the evaluation of safety and preliminary efficacy of 3′-Deoxy-3′-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas

T2 - Preliminary efficacy studies

AU - Spence, Alexander M.

AU - Muzi, Mark

AU - Link, Jeanne M.

AU - O'Sullivan, Finbarr

AU - Eary, Janet F.

AU - Hoffman, John M.

AU - Shankar, Lalitha K.

AU - Krohn, Kenneth A.

N1 - Funding Information: Acknowledgments. Pam Pham, Michele F. Wanner, Jeffrey Scharnhorst, and Neha Patel are gratefully acknowledged for their indispensable help. Supported by National Cancer Institute Contract N01-CM-37008 and NIH grants CA42045 and S10 RR17229.

PY - 2009

Y1 - 2009

N2 - Purpose: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-d-glucose (FDG). Procedures: Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [18F]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (KFLT), blood to tissue transport (K1), and phosphorylation (k3). FDG-PET scans were obtained 75-90 min postinjection. Results: KFLT and k3, but not K1 or k3/k2+k3, reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance. Conclusions: KFLT (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer.

AB - Purpose: 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-d-glucose (FDG). Procedures: Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [18F]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (KFLT), blood to tissue transport (K1), and phosphorylation (k3). FDG-PET scans were obtained 75-90 min postinjection. Results: KFLT and k3, but not K1 or k3/k2+k3, reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance. Conclusions: KFLT (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer.

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KW - Fluorothymidine

KW - Glioma

KW - Positron emission tomography (PET)

KW - Proliferation imaging

KW - Radionecrosis

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