Research ArticleBasic Science Investigation
Open Access

Evaluation of 134Ce/134La as a PET Imaging Theranostic Pair for 225Ac α-Radiotherapeutics

Kondapa Naidu Bobba, Anil P. Bidkar, Niranjan Meher, Cyril Fong, Anju Wadhwa, Suchi Dhrona, Alex Sorlin, Scott Bidlingmaier, Becka Shuere, Jiang He, David M. Wilson, Bin Liu, Youngho Seo, Henry F. VanBrocklin and Robert R. Flavell
Journal of Nuclear Medicine May 2023, 265355; DOI: https://doi.org/10.2967/jnumed.122.265355

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    (Left) Radiolabeling of MACROPA.NH2 and DOTA with 134CeCl3. (Right) Percentage radiolabeling at increasing L/M ratios for MACROPA.NH2 and DOTA (n = 2) at 25 °C, as assayed by radio-TLC.

  • FIGURE 2.
    FIGURE 2.

    Evaluation of PET imaging of 134Ce and chelated complexes in wild-type mouse studies. (A) Coronal small-animal PET/CT images of free 134CeCl3, 134Ce-MACROPA.NH2, and 134Ce-DOTA in wild-type mice. (B–D) Ex vivo biodistribution of 134CeCl3 (n = 2) and 225AcCl3 (n = 3) (B), 134Ce/225Ac-MACROPA.NH2 (n = 3) (C), and 134Ce/225Ac-DOTA (n = 3) (D). Error bars represent SD. ***P < 0.0008. ****P < 0.0001.

  • FIGURE 3.
    FIGURE 3.

    Radiolabeling of prostate cancer–targeting agents PSMA-617 and MACROPA-PEG4-YS5. (A) Radiolabeling of PSMA-617 (left) and radiolabeling yields at increasing molar ratios of PSMA-617 (right). (B) Radio-iTLC of 134Ce-PSMA-617 (left), same reaction mixture diluted in saline scanned without waiting for 1-h decay (middle), and same radio-iTLC scanned after 1-h decay showing quantitative radiochemical yield (right). (C) Radiolabeling of MACROPA-PEG4-YS5. (D) Radio-iTLC of 134Ce-MACROPA-PEG4-YS5 (left), same reaction mixture after PD10 column purification immediately scanned without waiting for 1-h decay (middle), and same radio-iTLC after 1-h decay (right). (E) 134La dechelation due to recoil effect. PBS = phosphate-buffered saline.

  • FIGURE 4.
    FIGURE 4.

    Small-animal PET imaging of 134Ce-PSMA-617 in 22Rv1 xenograft at 1 h after injection.

  • FIGURE 5.
    FIGURE 5.

    In vitro and in vivo analysis of radioimmunoconjugate 134Ce-MACROPA-PEG4-YS5. (A) Left: Magnetic bead–based radioligand assay for 134Ce-MACROPA-PEG4-YS5 (n = 3). Right: Saturation binding assay of 134Ce-MACROPA-PEG4-YS5 on 22Rv1 cells (dissociation constant, 3.7 nM) (n = 3). (B) Maximum-intensity-projection PET/CT and transverse small-animal PET/CT images obtained up to 7 d after 134Ce-MACROPA-PEG4-YS5 injection in mouse bearing 22Rv1 xenografts, demonstrating gradual increase in tumor uptake over time (n = 4). MIP = maximum-intensity projection.

  • FIGURE 6.
    FIGURE 6.

    Ex vivo biodistribution analysis of 134Ce/225Ac-MACROPA-PEG4-YS5 in mouse bearing 22Rv1 xenografts at 7 d after injection. Higher tumor and liver uptake was obtained. Error bars represent SD (n = 5 at 7 d and 2 at 14 d for 134Ce; n = 4 for 225Ac at 7 d).

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