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), Vol. 16:4
- Country of Publication:
- United States
- Language:
- English
Similar Records
A new potent radiosensitizer: 1-(2',3'-dideoxy-. cap alpha. -D-erythro-hex-2'-enopyranosyl)-2-nitroimidazole (RA-263)
Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR{sub 2}* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation
Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
RADIOSENSITIZERS
COMPARATIVE EVALUATIONS
ANOXIA
BRAIN
EXPERIMENTAL NEOPLASMS
FLUORINE 19
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMARY GLANDS
MICE
MISONIDAZOLE
NMR SPECTROMETERS
NUCLEAR MAGNETIC RESONANCE
OXIDOREDUCTASES
OXYGEN
RETENTION
SARCOMAS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BODY
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELEMENTS
ENZYMES
FLUORINE ISOTOPES
GLANDS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
MEASURING INSTRUMENTS
NEOPLASMS
NERVOUS SYSTEM
NONMETALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RESONANCE
RODENTS
SEPARATION PROCESSES
SPECTROMETERS
STABLE ISOTOPES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals
550603 - Medicine- External Radiation in Therapy- (1980-)