Dataset Information

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [¹¹C]K-2, in healthy human subjects.

ABSTRACT: [¹¹C]K-2, a radiotracer exhibiting high affinity and selectivity for ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [¹¹C]K-2 in various organs and calculate the effective dose after injection of [¹¹C]K-2 in healthy human subjects. Twelve healthy male subjects were registered and divided into two groups (370 or 555 MBq of [¹¹C]K-2), followed by 2 h whole-body scans. We estimated the radiation dose of each organ and then calculated the effective dose for each subject. The highest uptake of [¹¹C]K-2 was observed in the liver, while the brain also showed relatively high uptake. The urinary bladder exhibited the highest radiation dose. The kidneys and liver also showed high radiation doses after [¹¹C]K-2 injections. The effective dose of [¹¹C]K-2 ranged from 5.0 to 5.2 ?Sv/MBq. Our findings suggest that [¹¹C]K-2 is safe in terms of the radiation dose and adverse effects. The injection of 370-555 MBq (10 to 15 mCi) for PET studies using this radiotracer is applicable in healthy human subjects and enables serial PET scans in a single subject.

SUBMITTER: Hatano M

PROVIDER: S-EPMC7810729 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [11C]K-2, in healthy human subjects.

Hatano Mai M Miyazaki Tomoyuki T Ishiwata Yoshinobu Y Nakajima Waki W Arisawa Tetsu T Kuroki Yoko Y Kobayashi Ayako A Takada Yuuki Y Ogawa Matsuyoshi M Kawamura Kazunori K Zhang Ming-Rong MR Higuchi Makoto M Taguri Masataka M Kimura Yasuyuki Y Takahashi Takuya T

Scientific reports 20210115 1

[11C]K-2, a radiotracer exhibiting high affinity and selectivity for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [11C]K-2 in various organs and calculate the effective dose after injection of [11C]K-2 in healthy human subjects. Twelve he ...[more]

PMID: 33452361

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Project description:BackgroundImmunotherapy is a valuable option for cancer treatment, and the curative effect of anti-PD-1/PD-L1 therapy correlates closely with PD-L1 expression levels. Positron emission tomography (PET) imaging of PD-L1 expression is feasible using 68Ga-NOTA-Nb109 nanobody. 68Ga-NOTA-Nb109 was generated by radionuclide (68Ga) labeling of Nb109 using a NOTA chelator. To facilitate clinical trials, we explored the optimal dose range of 68Ga-NOTA-Nb109 in BALB/c A375-hPD-L1 tumor-burdened nude mice and C57-hPD-L1 transgenic MC38-hPD-L1 tumor-burdened mice by administration of a single intravenous dose of 68Ga-NOTA-Nb109 and confirmed the dose in cynomolgus monkeys. The biodistribution data of cynomolgus monkey PET images were extrapolated to estimate the radiation dose for the adult male and female using OLINDA2.1 software.Results68Ga-NOTA-Nb109 was stable in physiologic media and human serum. Ex vivo biodistribution studies showed rapid and specific uptake in A375-hPD-L1 or MC38-hPD-L1 tumors. The estimated ED50 was approximately 5.4 µg in humanized mice. The injected mass (0.3-100 µg in nude mice and approximately 1-100 µg in humanized mice) greatly influenced the general biodistribution, with a better tumor-to-background ratio acquired at lower doses of Nb109 (0.3-10 µg in nude mice and approximately 1 µg in humanized mice), indicating maximum uptake in tumors at administered mass doses below the estimated ED50. Therefore, a single 15-μg/kg dose was adopted for the PET/CT imaging in the cynomolgus monkey. The highest specific and persistent uptake of the tracer was detected in the spleen, except the levels in the kidney and urine bladder, which was related to metabolism and excretion. The spleen-to-muscle ratio of the tracer exceeded 10 from immediately to 4 h after administration, indicating that the dose was appropriate. The estimated effective dose was calculated to yield a radiation dose of 4.1 mSv to a patient after injecting 185 MBq of 68Ga-NOTA-Nb109.Conclusion68Ga-NOTA-Nb109 showed specific accumulation in hPD-L1 xenografts in ex vivo biodistribution studies and monkey PET/CT imaging. The dose escalation distribution data provided a recommended dose range for further use, and the safety of the tracer was confirmed in dosimetry studies.

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Dataset Information

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [¹¹C]K-2, in healthy human subjects.

Publications

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [<sup>11</sup>C]K-2, in healthy human subjects.

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