Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole

Wui Jin Koh, Janet S. Rasey, Margaret L. Evans, John R. Grierson, Thomas K. Lewellen, Michael M. Graham, Kenneth Krohn, Thomas W. Griffin

Research output: Contribution to journalArticle

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Abstract

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of ?1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.

Original languageEnglish (US)
Pages (from-to)199-212
Number of pages14
JournalInternational journal of radiation oncology, biology, physics
Volume22
Issue number1
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

hypoxia
tumors
Positron-Emission Tomography
positrons
Radiotherapy
radiation therapy
Neoplasms
tomography
dosimeters
drugs
Injections
injection
Fluorine
thresholds
fluoromisonidazole
Hypoxia
Tumor Burden
Pharmaceutical Preparations
Neck
Pharmacokinetics

Keywords

  • Positron emission transaxial tomography
  • Predictor of response
  • Tumor hypoxia
  • [F-18]fluoromisonidazole

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Koh, W. J., Rasey, J. S., Evans, M. L., Grierson, J. R., Lewellen, T. K., Graham, M. M., ... Griffin, T. W. (1992). Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. International journal of radiation oncology, biology, physics, 22(1), 199-212. https://doi.org/10.1016/0360-3016(92)91001-4

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. / Koh, Wui Jin; Rasey, Janet S.; Evans, Margaret L.; Grierson, John R.; Lewellen, Thomas K.; Graham, Michael M.; Krohn, Kenneth; Griffin, Thomas W.

In: International journal of radiation oncology, biology, physics, Vol. 22, No. 1, 1992, p. 199-212.

Research output: Contribution to journalArticle

Koh, WJ, Rasey, JS, Evans, ML, Grierson, JR, Lewellen, TK, Graham, MM, Krohn, K & Griffin, TW 1992, 'Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole', International journal of radiation oncology, biology, physics, vol. 22, no. 1, pp. 199-212. https://doi.org/10.1016/0360-3016(92)91001-4
Koh, Wui Jin ; Rasey, Janet S. ; Evans, Margaret L. ; Grierson, John R. ; Lewellen, Thomas K. ; Graham, Michael M. ; Krohn, Kenneth ; Griffin, Thomas W. / Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. In: International journal of radiation oncology, biology, physics. 1992 ; Vol. 22, No. 1. pp. 199-212.
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