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PET Used to Measure Efficacy of an Angiogenesis Inhibitor

PET Used to Measure Efficacy of an Angiogenesis Inhibitor

TORONTO —Results from a phase I study suggest that endostatin, an
inhibitor of angiogenesis, shows clear utility in treating cancer, but that
this effect does not continue to increase with larger doses. Moreover, in assessing efficacy, reduction of tumor size does not
provide the most useful immediate measure of the drug’s clinical benefit.

Nizar Mullani, speaking on behalf of his research team at The University of
Texas M.D. Anderson Cancer Center and Medical School, presented the findings at
the 48th Annual Meeting of the Society of Nuclear Medicine (abstract 1242).

Endostatin acts by inhibiting the replication of endothelial cells, which
form the walls of capillaries. Since tumors must form their own capillary
supply, drugs that inhibit endothelial cell division exert anticancer activity
indirectly, by preventing formation of new capillaries, thus starving the tumor
of nutrients.

Mr. Mullani and his colleagues examined the effects of intravenous
endostatin, administered daily to 18 cancer patients in doses ranging from 30
to 300 mg/m².

Positron emission tomography (PET) scans were done at baseline and after 28
and 56 days on endostatin. In these scans, fluorine-18-labeled
fluorodeoxyglucose (FDG) was used to estimate tumor metabolic rate, while
oxygen-15-labeled water served as the probe for imaging tumor blood flow. In
addition, tumor size was measured by CT scan at the 28-day time point.

Figure 1 shows PET scans of a liver tumor. The enhanced metabolism
associated with the cancer is clearly visible in the FDG panel. In this
example, the tumor does not show any increased blood flow, compared with the
rest of the liver. Any such changes would be visible, as shown by the increase
in brightness associated with higher blood flow in the spleen (seen to the
right of the liver).

Figure 2 summarizes the data for tumor blood flow and metabolic rate at 28
and 56 days post-treatment, and tumor size at 28 days post-treatment.

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