Research ArticleClinical Investigation
Open Access

First-in-Human Study of 18F-Labeled PET Tracer for Glutamate AMPA Receptor [18F]K-40: A Derivative of [11C]K-2

Sadamitsu Ichijo, Tetsu Arisawa, Mai Hatano, Waki Nakajima, Tomoyuki Miyazaki, Tsuyoshi Eiro, Yuuki Takada, Ryunosuke Iai, Akane Sano, Masaki Sonoda, Yutaro Takayama, Yuichi Kimura and Takuya Takahashi
Journal of Nuclear Medicine May 2025, jnumed.124.269405; DOI: https://doi.org/10.2967/jnumed.124.269405

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Chemical structures of [18F]K-40, [18F]K-40OH, [11C]K-2, and [11C]K-2OH.

  • FIGURE 2.
    FIGURE 2.

    Averaged pTAC (left panels) and metabolic rate (right panels) of [18F]K-40 and [11C]K-2. Studies for [18F]K-40 (n = 5) (A). Studies for [11C]K-2 (n = 6) (B). Data in (B) were obtained from previous study (20). Data are shown as mean ± SD.

  • FIGURE 3.
    FIGURE 3.

    (A) Averaged time–activity curve in brain regions of healthy subjects injected with [18F]K-40 (n = 5). (B) Typical LGA plots. Estimated amount of K-40 and K-40OH was integrated in left panel, and estimated amount of K-40OH was integrated in right panel. Data are shown as mean ± SD. C and Cp are time–activity curves in tissue and arterial plasma. Cp is combined radioactivity of K-40 and K-40OH (B, left) and radioactivity of K-40OH (B, right).

  • FIGURE 4.
    FIGURE 4.

    (A) VT values of various brain regions computed with pTAC from LGA plots in [18F]K-40 PET study. (B) BPND values of various brain regions calculated with Logan plot analysis using white matter as reference region (without pTAC). (C) Linear regression analysis between VT of brain regions (except white matter) computed with pTAC and BPND using white matter as reference. (D) Comparison of VT value, which corresponds to zero point of BPND, using white matter as reference (x intercept of plot in (C)) and VT of white matter computed with pTAC. n = 5. (A and B) Data are shown as mean ± SD. HC = healthy control.

  • FIGURE 5.
    FIGURE 5.

    (A) Comparison between [11C]K-2 BPND PET images and [18F]K-40 BPND PET images. (B) Correlation between [11C]K-2 and [18F]K-40 BPND values in brain regions in healthy subjects. HC = healthy control.

  • FIGURE 6.
    FIGURE 6.

    (A) Change in limit of agreement on difference in BPND and SUVR with varying scan start time wherein frame width is fixed at 10 min. (B) Correlation between BPND value and SUVR40–50min−1 in brain regions in healthy subjects. (C) Comparison between [18F]K-40 BPND PET images and [18F]K-40 SUVR PET images at 40–50 min.

Tables

  • TABLE 1.

    Specification of [18F]K-40

    TestSpecification
    1. Quantity
     1.1 Volume of one batch18–22 mL
     1.2 RadioactivityNLT 1.85 GBq
     1.3 K-40 concentrationNMT 10 μg/mL
     1.4 Specific radioactivityNLT 37 GBq/μmol on EOS
     1.5 Half-lifeNLT 105 min; NMT 115 min
    2. Property
     2.1 AppearanceColorless to light yellow solution
     2.2 ParticleFree of visible particulate matter
    3. Bacterial endotoxinNMT 150 EU/whole solution
    4. SterilityNo growth
    5. pHNLT 5.0; NMT 8.0
    6. Qualitative analysis
     6.1 γ-spectrum*511-keV peak detected
     6.2 Radiochemical identityRadiometric RT ratio of [18F]K-40 to K-40 standard: 1.0 ± 0.1
    7. Purity
     7.1 Other radioisotope*No peak except 511 keV and 1,022 keV
     7.2 Radiochemical purityNMT 95%
    8. Residual solvent
     8.1 MethanolNLT 3,000 ppm
     8.2 AcetonitrileNLT 410 ppm
     8.3 DMSONLT 5,000 ppm
    9. Assay of ethanolNLT 6%; NMT 10%

    • ↵* All tests are required for every production (6.1 and 7.1 are required once/year).

    • NLT = not less than; NMT = not more than; EOS = end of synthesis; RT = retention time; DMSO = dimethylsulfoxide.

  • TABLE 2.

    Specification of [11C]K-2

    TestSpecification
    1. Quantity
     1.1 Volume of one batch13–17 mL
     1.2 RadioactivityNLT 1.85 GBq
     1.3 K-2 concentrationNMT 10 μg/mL
     1.4 Specific radioactivityNLT 37 GBq/μmol on EOS
     1.5 Half-lifeNLT 19.0 min; NMT 21.0 min
    2. Property
     2.1 AppearanceColorless to light yellow solution
     2.2 ParticleFree of visible particulate matter
    3. Bacterial endotoxinNMT 150 EU/whole solution
    4. SterilityNo growth
    5. pHNLT 5.0; NMT 8.0
    6. Qualitative analysis
     6.1 γ-spectrum*511-keV peak detected
     6.2 Radiochemical identityRadiometric RT ratio of [11C]K-2 to K-2 standard: 1.0 ± 0.1
    7. Purity
     7.1 Other radioisotope*No peak except 511 keV and 1,022 keV
     7.2 Radiochemical purityNMT 95%
    8. Residual solvent
     8.1 AcetonitrileNLT 410 ppm
     8.2 DMFNLT 880 ppm
    9. Assay of ethanolNLT 3%, NMT 6%

    • ↵* All tests are required for every production (6.1 and 7.1 are required once/year).

    • NLT = not less than; NMT = not more than; EOS = end of synthesis; RT = retention time; DMF = dimethylformamide.

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