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. 2025 May 14;15(1):57.
doi: 10.1186/s13550-025-01221-x.

Radiation dosimetry of [11C]TZ1964B as determined by whole-body PET imaging of nonhuman primates

Baijayanta Maiti  1   2 , Noah L Goldman  3 , Mahdjoub Hamdi  4 , Jason Lenox-Krug  3 , Morvarid Karimi  3 , Stephen M Moerlein  4 , Richard Laforest  4 , Tianyu Huang  4 , Zhude Tu  3   4 , Joel S Perlmutter  3   4   5   6   7 , Scott A Norris  3   4
Affiliations

Radiation dosimetry of [11C]TZ1964B as determined by whole-body PET imaging of nonhuman primates

Baijayanta Maiti et al. EJNMMI Res. .

Abstract

Background: Phosphodiesterase 10A (PDE10A) is a postsynaptic, membrane bound cyclic nucleotide phosphodiesterase that is highly enriched in the striatal medium spiny neurons and regulates dopaminergic neurotransmission. The objective of this study is to determine the absorbed radiation dosimetry of a novel radiotracer for PDE10A: 3-(Methoxy-11C)-2-((4-(1-methyl-4-(pyridine-4yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinolone ([11C]TZ1964B) based on whole body PET imaging in nonhuman primates, a critical step before translating this radiotracer to imaging studies in humans. [11C]TZ1964B may contribute to the clinical investigation of multiple neuropsychiatric conditions including Parkinson disease, Huntington disease and schizophrenia. For absorbed radiation measures, two males and one female cynomolgus monkeys (Macaca fascicularis) had intravenous injections of 302.3-384.4 MBq of [11C]TZ1964B followed by sequential whole body PET imaging in a MicroPET-Focus220 scanner. Volumes of interest (VOIs) that either encompassed the entire organ or sampled regions of highest activity within larger organs were defined. Time-activity curves were derived from the PET data for each VOI, and analytical integration of its multi-exponential fit yielded the organ time-integrated activity. We generated human radiation dose estimates based on the scaled organ residence using OLINDA/EXM2.2.

Results: Highest retention was observed in the liver with total time-integrated activity of ~ 0.23 h. Absorbed organ dosimetry was highest in the liver (53.3 μGy/MBq), making it the critical organ. Gallbladder (35.9 μGy/MBq) and spleen (35.4 μGy/MBq) were the next highest organs for absorbed radiation dose. Effective doses were estimated to be 5.02 and 5.84 μSv/MBq for males and females, respectively.

Conclusions: This nonhuman primate dosimetry study suggests intravenous doses up to 938 MBq of [11C]TZ1964B can be safely administered to human subjects for PET measurements of PDE10A activity. The tracer kinetic data is consistent with a hepatobiliary clearance pathway for the radiotracer.

Keywords: Dosimetry; PDE10A; PET; [11C]TZ1964B.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This article does not contain any studies with human participants performed by any of the authors. We used the minimum number of animals necessary for this study, and in accordance with the recommendations of the Weatherall report “The use of non-human primates in research,” and took all steps to ameliorate suffering in our studies. Guidelines prescribed by the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animal were followed, and this work had the approval the Institutional Animal Care and Use Committee (IACUC; study numbers: 20150166 and 20180143) at Washington University in St. Louis. All animals were housed individually; maintained in facilities with 12-h dark and light cycles; provided access to food and water ad libitum; and were equally engaged with a variety of psychologically-enriching tasks, such as watching movies or playing with appropriate toys. Consent for publication: Not applicable. Competing Interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Outline of scanning sequence: Seven to eight successive PET scans of increasing duration were obtained to cover A (whole brain), B (heart and lungs), C (liver, gallbladder and kidneys), and D (urinary bladder, small and large intestines)
Fig. 2
Fig. 2
Time-activity curves with activity expressed in percentage of injected dose per organ. The non-decay corrected representative organ time-activity curves from scans in the two male macaques and from two scan sessions obtained 3 years apart in the same female macaque are shown here. Area under the curve for bladder and gallbladder uptake from scan#1 and scan#2 from the female monkey had a poor exponential fit and were integrated using the trapezoid method
See this image and copyright information in PMC

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