Research ArticleRadiochemistry
Open Access

One-Step 18F-Labeling and Preclinical Evaluation of Prostate-Specific Membrane Antigen Trifluoroborate Probes for Cancer Imaging

Hsiou-Ting Kuo, Mathieu L. Lepage, Kuo-Shyan Lin, Jinhe Pan, Zhengxing Zhang, Zhibo Liu, Alla Pryyma, Chengcheng Zhang, Helen Merkens, Aron Roxin, David M. Perrin and François Bénard
Journal of Nuclear Medicine August 2019, 60 (8) 1160-1166; DOI: https://doi.org/10.2967/jnumed.118.216598

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Trifluoroborate probes resembling scaffolds of DCFPhL, DCFPyL, and PSMA-617. In red: AMBF3 prosthetic; in blue: pyrBF3 prosthetic.

  • FIGURE 2.
    FIGURE 2.

    (A) Competitive inhibition curves of DCFPyL and 1–8. (B) Values of LogD7.4 for DCFPyL and 1–8 (error bars reflect SD).

  • FIGURE 3.
    FIGURE 3.

    PET/CT images (maximum-intensity projections) of LNCaP tumor–bearing mice at 1 h after injection, with and without blocking by coinjection of unlabeled DCFPyL. Arrows locate tumors.

  • FIGURE 4.
    FIGURE 4.

    Uptake values for tumor (A), kidney (B), and intestine (C) for compounds 1–8 and DCFPyL; in black: DCFPyL; in red: AMBF3 derivatives; in blue: pyrBF3 derivatives (error bars reflect SD values, significance of differences with 18F-DCFPyL indicated at top of bars: **P < 0.01; ****P < 0.0001; ns = not significant). Full data available in Supplemental Data section.

  • FIGURE 5.
    FIGURE 5.

    Contrast ratios (tumor-to-muscle in A and tumor-to-blood in B) for compounds 1–8 and DCFPyL at 1 h after injection; in black: DCFPyL; in red: AMBF3 derivatives; in blue: pyrBF3 derivatives (error bars reflect SD values, significance of differences with 18F-DCFPyL indicated at top of bars: ****P < 0.0001).

  • FIGURE 6.
    FIGURE 6.

    PET/CT images (maximum-intensity projections in black on white to display background activity), comparing 18F-DCFPyL (A) with 18F-8 (B), showing similar image contrast with lower liver accumulation for compound 8. Maximum of scale corresponds to 10 %ID/g for both radiotracers.

Tables

  • TABLE 1

    Activity Yield, Molar Activity, Partition Coefficient, and Binding Affinity of 18F-Labeled PSMA Radiotracers

    TracerActivity yield* (%, isolated)Molar activity† (GBq/μmol)LogD7.4 (n = 3)Ki (nM) (n = 3)
    18F-DCFPyL12 ± 3 (n = 7)118 ± 37 (n = 7)−3.12 ± 0.222.0 ± 0.8
    18F-17 ± 4 (n = 4)70 ± 19 (n = 4)−3.43 ± 0.3514.4 ± 2.7
    18F-24 ± 2 (n = 3)89 ± 26 (n = 3)−4.26 ± 0.0411.8 ± 0.9
    18F-35 ± 1 (n = 3)56 ± 15 (n = 3)−4.01 ± 0.1425.9 ± 5.7
    18F-416 ± 2 (n = 3)148 ± 89 (n = 3)−3.34 ± 0.0227.6 ± 3.8
    18F-513 ± 10 (n = 2)137 ± 22 (n = 2)−3.52 ± 0.211.14 ± 0.26
    18F-615 ± 2 (n = 6)278 ± 73 (n = 6)−2.28 ± 0.011.90 ± 0.68
    18F-710 ± 5 (n = 3)92 ± 22 (n = 2)−3.24 ± 0.0316.5 ± 5.5
    18F-87 ± 6 (n = 3)211 ± 48 (n = 3)−3.58 ± 0.360.22 ± 0.01

    • ↵* Activity yields are reported at end of synthesis (1 h for DCFPyL, 40 min for 1–8) (with no correction for decay).

    • ↵† Molar activities are reported at time of quality control injection, shortly after end of synthesis.

  • TABLE 2

    Changes in Activity Yield and Molar Activity with Higher Quantities of Precursor Material

    TracerActivity yield (%)Molar activity (GBq/μmol)
    18F-2 from 100 nmol (n = 3)4 ± 289 ± 26
    18F-2 from 1000 nmol (n = 2)34 ± 913.3 ± 0.74
    Change× 8.5÷ 6.7

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