18F-ISO-1 shows promise for imaging cell proliferation

The first human study of the cell proliferation marker F18-ISO-1 indicated its safety and feasibility and suggested it may be used to stratify patients into high and low Ki-67 proliferative groups. The study was published online Jan. 28 in The Journal of Nuclear Medicine.

Measurements of cell proliferation can be used to predict and determine response to therapy and may inform the development of new agents. F18-FLT, a PET proliferation marker, underestimates the proliferative status of solid tumors. Ki-67 provides a marker for all phases of the cell cycle, but it requires a biopsy specimen or surgical resection, which is not possible for all tumors. Consequently, there is a need for a noninvasive means to measure the proliferative status of solid tumors.

Farrokh Dehdashti, MD, a professor in the radiology department at the Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis, Mo., and colleagues sought to evaluate the safety and feasibility of F18-ISO-1 PET imaging, estimate its dosimetry and correlate the marker with tumor tissue assays of Ki-67.

The researchers enrolled 30 patients newly diagnosed with primary breast cancer, head and neck cancer or lymphoma.

Dehdashti and colleagues used receiver-operator-characteristic analysis to determine a Ki-67 of 35 percent provided the best cutoff to distinguish between tumors with high and low Ki-67. They observed significant correlation between tumor Ki-67 and F18-ISO-1 uptake by tumor-to-muscle activity ratios and maximum standard uptake value.

However, they did not detect significant correlation between Ki-67 and F18-ISO-1 uptake measured by distribution volume ratio or tumor-to-normal tissue ratio, which may be related to the variability of normal-tissue uptake.

The researchers assessed organ activity data for the liver, spleen, pancreas, lung, kidneys, brain, heart, gallbladder, small intestines and urinary bladder. The average accumulation over the 3.5 hour imaging period was highest in the gallbladder, pancreas and liver. The dosimetry estimates a maximum of 550 MBq can be injected and will yield an effective dose of 8.6 mSv.

“The high correlation of tumor-to-muscle ratio with Ki-67 scores indicates that F18-ISO-1 may provide an imaging alternative to biopsy specimens for obtaining this measurement,” Dehdashti et al wrote. “The observation that F18-ISO-1 can stratify patients into groups of high (Ki-67 > 35 percent) and low (Ki-67 < 35 percent) proliferative status is expected to be useful in selecting patients who are likely to respond to chemotherapies that target cycling cancer cells.”