Human biodistribution and dosimetry of ¹¹C-CUMI-101, an agonist radioligand for serotonin-1a receptors in brain

Abstract

As a reported agonist, ¹¹C-CUMI-101 is believed to selectively bind the G-protein-coupled state of the serotonin-1A (5-HT(1A)) receptor, thereby providing a measure of the active subset of all 5-HT(1A) receptors in brain. Although ¹¹C-CUMI-101 has been successfully used to quantify 5-HT(1A) receptors in human and monkey brain, its radiation exposure has not previously been reported. The purpose of this study was to calculate the radiation exposure to organs of the body based on serial whole-body imaging with positron emission tomography (PET) in human subjects.

Methods: Nine healthy volunteers were injected with 428±84 MBq (mean ± SD) (11)C-CUMI-101 and then imaged with a PET-only device for two hours from head to mid-thigh. Eleven source organs (brain, heart, liver, pancreas, stomach, spleen, lungs, kidneys, lumbar spine L1-5, thyroid, and urinary bladder) were identified on whole body images and used to calculate radiation doses using the software program OLINDA/EXM 1.1. To confirm that we had correctly identified the pancreas, a tenth subject was imaged on a PET/CT device.

Results: Brain had high uptake (∼11% of injected activity (IA)) at 10 min. Although liver had the highest uptake (∼35% IA at 120 min), excretion of this activity was not visible in gall bladder or intestine during the scanning session. Organs which received the highest doses (microSv/MBq) were pancreas (32.0), liver (18.4), and spleen (14.5). The effective dose of ¹¹C-CUMI-101 was 5.3±0.5 microSv/MBq.

Conclusion: The peak brain uptake (∼11% IA) of ¹¹C-CUMI-101 is the highest among more than twenty ¹¹C-labeled ligands reported in the literature and provides good counting statistics from relatively low injected activities. Similar to that of other ¹¹C-labeled ligands for brain imaging, the effective dose of ¹¹C-CUMI-101 is 5.3±0.5 microSv/MBq, a value that can now be used to estimate the radiation risks in future research studies.

Figure 1. Biodistribution of radioactivity in a female healthy volunteer after injecting ¹¹C-CUMI-101 (585 MBq).

The high activity at 18 min in the upper left quadrant and adjacent to the liver was thought to be stomach. These planar images are compressed in the coronal direction at the specified times. The right side of the person is on the left side of the image.

Figure 2. Time-activity curves for identifiable organs after injection of ¹¹C-CUMI-101.

A: Liver (•), Brain (▵), and Lungs (▪). B: Pancreas (•), Stomach (▵), and Spleen (▪). C: Kidneys (•), Urinary Bladder (▵), and Heart (▪). D: Bone Marrow (•), Salivary Glands (▵), and Thyroid (▪). Data are the average determined in nine healthy volunteers and are corrected for radioactive decay. SD bars are not included to avoid cluttering the graph, but coefficient of variance is reported for residence time, which reflects the area under these time-activity curves (Table 2).

Figure 3. PET-CT of abdomen at approximately 30 minutes after injection of ¹¹C-CUMI-101 (369 MBq) shows high uptake in pancreas.

A: Axial CT of abdomen, with right side of subject on left, and anterior aspect facing upward on page. B: PET image of same cross-section, showing high uptake of ¹¹C-CUMI-101 in pancreas and liver. C: Fused PET-CT image confirms that radioactive signal on the left is at anatomical location of pancreas (pink arrow).