technetium-tc-99m-exametazime and iodoazomycin-arabinoside

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

Topics: Animals; Autoradiography; Cell Hypoxia; Cerebrovascular Circulation; Cerebrovascular Disorders; Diffusion; Disease Models, Animal; Magnetic Resonance Imaging; Male; Nitroimidazoles; Rats; Rats, Wistar; Technetium Tc 99m Exametazime

Current routine clinical techniques, including angiography and perfusional single-photon emission tomography, can be used to indicate problems in cerebral vascular supply and areas of cerebral hypoperfusion following a stroke, but cannot distinguish between ischaemic core and penumbra. In order to image specifically the penumbra, a method or indicator should be able to define areas with reduced blood flow, and a degree of metabolic compromise. In this context, the tissue could be regarded as hypoxic rather than ischaemic, and we have therefore chosen to investigate the potential of radio-labelled hypoxic markers in the study of ischaemia. In order to combine a hypoxic marker with a blood flow marker we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and iodine-125 iodoazomycin arabinoside (125I-IAZA), during cerebral ischaemia in the rat middle cerebral artery occlusion model. 99mTc-HMPAO and 125I-IAZA were injected simultaneously 2 h following occlusion of the middle cerebral artery, and 5 h before decapitation. Paired autoradiograms were produced and compared. Three distinct patterns emerged from the autoradiograms: slightly decreased perfusion with no uptake of the hypoxic marker indicating an area of misery perfusion; moderately decreased perfusion with concomitant uptake of iodoazomycin arabinoside, a region of hypoxia; and severely decreased perfusion with no retention of the hypoxic tracer. In conclusion, we present a new use for an imaging agent in the investigation of cerebral hypoxia. This agent, IAZA together with HMPAO, provides a means of separating the penumbra into regions of misery perfusion and hypoxia. The potential impact of this may be important in the clinical investigation of stroke.

Topics: Animals; Brain; Brain Ischemia; Cell Hypoxia; Cerebrovascular Circulation; Iodine Radioisotopes; Male; Nitroimidazoles; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Rats; Rats, Wistar; Technetium Tc 99m Exametazime

Tumor perfusion and oxygenation status have been suggested as factors which may influence treatment outcome in cancer patients. Nuclear medicine assays of tumor perfusion [99mTc-hexamethylpropylenamine oxime (HMPAO)] and tumor hypoxia [123I-iodoazomycin arabinoside (IAZA)] have recently been developed and described. We report on measurements of perfusion and oxygenation status of 27 tumors in 22 patients using these probes. An inverse correlation between tumor uptake of HMPAO and IAZA was measured (p < 0.05), with severe perfusion deficit usually associated with an increased uptake of the hypoxic marker. This trend was observed for limited stage small-cell lung carcinoma, squamous-cell carcinoma of the head and neck, soft-tissue sarcoma, brain metastases from small-cell lung carcinoma and adenocarcinoma of the prostate as a group, but not for glioblastoma multiforme. Whereas each imaging agent can yield information about the physiological status of tumor and normal tissue, the information resulting from their combined use could be important in cancer therapy.

Topics: Brain Neoplasms; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Hypoxia; Female; Glioblastoma; Head and Neck Neoplasms; Humans; Iodine Radioisotopes; Lung Neoplasms; Male; Nitroimidazoles; Organotechnetium Compounds; Oximes; Sarcoma; Soft Tissue Neoplasms; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon