Demonstration of tumor-selective retention of fluorinated nitroimidazole probes by /sup 19/F magnetic resonance spectroscopy in vivo
We have evaluated two fluorinated misonidazole analogues, Ro 07-0741 and CCI-103F, as potential probes for the non-invasive identification of hypoxic tumor cells by /sup 19/F magnetic resonance spectroscopy (MRS) in vivo. The equipment used was a 1.9 T Oxford Research Systems TMR-32 spectrometer, fitted with a 15 mm diameter surface coil. Signal was readily detectable, with similar intensity from EMT6 tumor, liver, and brain at early times (1-2 hr) after i.v. injection in BALB/c mice, indicative of an initial uniform biodistribution of parent probes. At later times (5-10 hr) there was a progressive reduction in signal intensity from brain and liver, but tumor levels remained constant or declined more slowly. This is illustrated by tumor/brain ratios at 6-7 hr of 2.9 (Ro 07-0741) and 4.2 (CCI-103F). In 4/5 mice analyzed at 20-24 hr after Ro 07-0741, and 1/2 following CCI-103F, tumor signal remained detectable. This occurred in the absence of parent probe as measured by HPLC, suggesting the involvement of a product of nitroreductive bioactivation. Studies with KHT and RIF-1 tumors in C3H/He mice showed a similar trend but retention in RIF-1 was less dramatic, and this was consistent with the known hypoxic fractions and comparative in vivo nitroreductase activities. These promising results support the continuing development of /sup 19/F nitroimidazole probes for non-invasive identification of hypoxic cells in vivo.
- Research Organization:
- St George's Hospital Medical School, London (England)
- OSTI ID:
- 6252892
- Journal Information:
- Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 16:4; ISSN IOBPD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560152* -- Radiation Effects on Animals-- Animals
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
COMPARATIVE EVALUATIONS
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELEMENTS
ENZYMES
EXPERIMENTAL NEOPLASMS
FLUORINE 19
FLUORINE ISOTOPES
GLANDS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAGNETIC RESONANCE
MAMMALS
MAMMARY GLANDS
MEASURING INSTRUMENTS
MICE
MISONIDAZOLE
NEOPLASMS
NERVOUS SYSTEM
NMR SPECTROMETERS
NONMETALS
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN
RADIOSENSITIZERS
RESONANCE
RETENTION
RODENTS
SARCOMAS
SEPARATION PROCESSES
SPECTROMETERS
STABLE ISOTOPES
TUMOR CELLS
VERTEBRATES