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Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys

Abstract

Purpose

4-[18F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken.

Methods

Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 μg/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 μg/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[18F]-ADAM (182±8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time–activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software.

Results

In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 μSv/MBq, respectively.

Conclusion

Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[18F]-ADAM is safe for use in human PET imaging studies.

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Acknowledgments

We thank the Institute of Nuclear Energy Research of Taiwan for providing the OLINDA 1.0/EXM computer program. The synthesis of 4-F-ADAM was funded by the National Institute of Mental Health (NIMH) under contract no. NO1-MH-32005. Toxicology studies were also funded by NIMH, under contract no. M422-05. This work was supported by the National Science Council of Taiwan (grants NSC 95-2811-B-016-002, 95-2321-B-016-001-MY2 and 96-2811-B-016-004).

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Correspondence to Chyng-Yann Shiue.

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Huang, YY., Ma, KH., Tseng, TW. et al. Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys. Eur J Nucl Med Mol Imaging 37, 545–555 (2010). https://doi.org/10.1007/s00259-009-1281-z

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Keywords

  • 4-[18F]-ADAM
  • Serotonin transporter imaging agent
  • Toxicity
  • Radiation dosimetry