Initial clinical trials of carbon-11-labeled 4DST in brain tumors

Objectives As uncontrolled cell proliferation is an integral part of the cancer phenotype and measuring the DNA synthesis rate is still considered the gold standard for characterizing cell proliferation, measurement of the DNA synthesis rate of tumor tissues in vivo is an important goal of tumor diagnosis. Recently, we developed [methyl-¹¹C]4′-thiothymidine ([¹¹C]4DST) as an in vivo DNA synthesis marker. In this first clinical trials, we aimed to determine the safety, and initial brain tumor imaging with [¹¹C]4DST in human subjects.

Methods Five patients with brain tumors underwent dynamic [¹¹C]4DST scans with arterial blood sampling. The [¹¹C]methionine ([¹¹C]MET) PET scan was also performed in the same day. Metabolites in plasma and urine samples were analyzed by HPLC. Breakdown of the blood - brain barrier in tumor tissue was confirmed by Gd-MRI.

Results There were no serious adverse events in all the patients throughout the study period. [¹¹C]4DST showed little uptake in the normal brain, resulting in low background for imaging of brain tumors. [¹¹C]4DST PET demonstrated rapid uptake and retention of radioactivity in aggressive tumor masses, while no signal was seen in clinically stable disease in which [¹¹C]MET uptake was clear. Analysis of plasma samples by HPLC indicated that more than 40% of the radioactivity was present as unchanged [¹¹C]4DST at 30 min post injection. Patlak plots showed a linear increase, indicating irreversible trapping of [¹¹C]4DST in tumor tissues.

Conclusions The initial findings of the present study in a small group of patients indicated that [¹¹C]4DST PET is feasible for imaging brain tumors