Research ArticleBasic Science Investigations

Promises of Cyclotron-Produced 44Sc as a Diagnostic Match for Trivalent β−-Emitters: In Vitro and In Vivo Study of a 44Sc-DOTA-Folate Conjugate

Cristina Müller, Maruta Bunka, Josefine Reber, Cindy Fischer, Konstantin Zhernosekov, Andreas Türler and Roger Schibli
Journal of Nuclear Medicine December 2013, 54 (12) 2168-2174; DOI: https://doi.org/10.2967/jnumed.113.123810

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Nuclear reaction for production of 44Sc from enriched 44Ca targets. (B) γ-ray spectrum of 44Sc obtained from irradiated 44Ca targets 5 h after end of beam.

  • FIGURE 2.
    FIGURE 2.

    Chemical structure of DOTA-folate conjugate (cm09) and preparation of 44Sc-cm09.

  • FIGURE 3.
    FIGURE 3.

    (A) Cell uptake and internalization of 44Sc-cm09 (green) and 177Lu-cm09 (red) after incubation time of 2 or 4 h at 37°C, respectively. (B) Time-dependent internalization of 44Sc-cm09 (green) and 177Lu-cm09 (red) over 4 h.

  • FIGURE 4.
    FIGURE 4.

    (A) Tumor-to-background ratios 4 h after injection of 44Sc-cm09 (green) and 177Lu-cm09 (red). (B) Tumor-to-background ratios 20 h after injection of 44Sc-cm09 (green) and 24 h 177Lu-cm09 (red). Blood clearance (C), liver clearance (D), lung clearance (E), and spleen clearance (F) of 44Sc-cm09, compared with 177Lu-cm09 (the %ID/g values at 2 h after injection were set to 100%).

  • FIGURE 5.
    FIGURE 5.

    (A) PET/CT image of KB tumor–bearing mouse 4 h after injection of approximately 25 MBq of 44Sc-cm09. (B) SPECT/CT image of KB tumor–bearing mouse 4 h after injection of approximately 35 MBq of 177Lu-cm09 (23). Tumors (Tu) are indicated with red arrows, kidneys (Ki) are indicated with yellow arrows, and urinary bladder (Bl) is indicated with white arrow.

Tables

  • TABLE 1

    Biodistribution of 44Sc-cm09 in KB Tumor–Bearing Female Nude Mice

    44Sc-cm09 (% injected dose per gram tissue*)
    Organ2 h after injection4 h after injection8 h after injection20 h after injection
    Blood3.74 ± 0.882.67 ± 0.351.77 ± 0.100.87 ± 0.08
    Lung2.29 ± 0.421.84 ± 0.211.40 ± 0.100.90 ± 0.12
    Spleen1.05 ± 0.190.90 ± 0.120.77 ± 0.010.70 ± 0.14
    Kidneys19.21 ± 1.7022.61 ± 4.5221.30 ± 4.6222.22 ± 1.94
    Stomach1.19 ± 0.171.01 ± 0.060.81 ± 0.030.58 ± 0.02
    Intestines0.59 ± 0.160.53 ± 0.090.38 ± 0.050.36 ± 0.12
    Liver3.63 ± 0.193.12 ± 0.383.56 ± 0.552.31 ± 0.15
    Salivary glands6.49 ± 0.526.48 ± 0.294.51 ± 0.533.48 ± 0.57
    Muscle1.07 ± 0.031.30 ± 0.611.12 ± 0.370.76 ± 0.28
    Bone0.98 ± 0.041.04 ± 0.160.92 ± 0.0.90.68 ± 0.05
    Tumor8.37 ± 0.4112.51 ± 1.7412.43 ± 1.0414.05 ± 2.29
    Tumor to blood2.50 ± 0.593.79 ± 1.887.03 ± 0.6416.07 ± 1.71
    Tumor to liver2.31 ± 0.113.25 ± 1.623.34 ± 0.436.07 ± 0.72
    Tumor to kidney0.44 ± 0.030.45 ± 0.230.59 ± 0.060.63 ± 0.07

    • ↵* Values shown represent mean ± SD of data from 3 animals (n = 3) per cohort.

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