Researchers have found the newly developed radiopharmaceutical C-4DST safe and effective for imaging brain tumors in a pilot study published Aug. 1 in the Journal of Nuclear Medicine.
Jun Toyohara, Positron Medical Center, Tokyo Metropolitan Institute of Gerontoloy, Tokyo, and colleagues assessed C-4DST's multiorgan biodistribution and radiation dosimetry in three healthy humans and six patients with brain tumors, according to the study.
The three healthy volunteers were free of somatic and neuropsychiatric illnesses, according to their medical histories and, of the six patients with brain tumors, three had grade 3 astrocytoma, one had grade 3 oligodendroglioma, one had a metastatic brain tumor of lung cancer origin and one had malignant lymphoma.
Safety data were collected from five of the six patients with brain tumors after administering C-4DST and throughout a one-week follow-up period. The monitoring included records of adverse events, changes in vital signs, physical exam findings, ECG findings and laboratory parameters. Vital signs were closely-monitored during administration, and blood tests were administered before and after. The protocol for the three healthy patients was “essentially the same,” according to the study.
The authors noted the transient asymptomatic increases in blood pressure in two of the nine patients after the PET scan, which they attributed to discomfort from the head immobilization device, positioning and the need to hold still for the long period of the exam.
“Administration of C-4DST was well tolerated by all subjects,” wrote Toyohara et al. “No drug-related adverse events were reported in this study. No clinically important trends indicative of a safety signal were noted for laboratory parameters, vital signs or electrocardiogram parameters.”
In the whole-body imaging, the kidneys showed the highest uptake of radioactivity, which rapidly decreased and entered the urinary bladder. The next-highest uptake was in the liver, followed by a gradual decrease. The researchers reported that they could not identify any reversible loss of radioactivity in the proliferating tissues during the 120-minute scan. Non-proliferating tissues show the lowest uptake, the authors noted.
C-4DST showed little uptake in the normal brain, resulting in a low background activity for imaging of brain tumors, according to study. “Physiologic uptake was observed in salivary glands and proliferating tissues, nasal mucosa, and bone marrow. Tumors in newly identified or aggressively growing masses confirmed by serial Gd-MRI were clearly visualized by C-4DST.
“We found C-4DST PET to be safe and well tolerated, with no adverse events in the nine subjects studied. The radiation-absorbed dose was higher in the urinary bladder wall, liver, and kidney than in other organs studied but was nonetheless sufficiently low for clinical use,” wrote Toyohara et al.
The researchers found low background levels of radioactivity in the whole-body imaging and determined that it may be useful for the detection of head and neck tumors, lung and abdominal tumors and sarcomas. “Dosimetry and pharmacologic safety were acceptable at the dose required for adequate PET images,” the authors concluded. However, to confirm whether C-4DST is a useful cell proliferation marker in humans would require further study.