Research ArticleBasic Science Investigation

Administration Routes for SSTR-/PSMA- and FAP-Directed Theranostic Radioligands in Mice

Jasmin M. Klose, Jasmin Wosniack, Janette Iking, Magdalena Staniszewska, Fadi Zarrad, Marija Trajkovic-Arsic, Ken Herrmann, Pedro Fragoso Costa, Katharina Lueckerath and Wolfgang P. Fendler
Journal of Nuclear Medicine September 2022, 63 (9) 1357-1363; DOI: https://doi.org/10.2967/jnumed.121.263453

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    Activity at application site and systemic availability over time in healthy mice. Retention of 68Ga-DOTATOC (A), 68Ga-PSMA11 (B), and 68Ga-FAPI46 (C) is shown in healthy mice (6/group) at application site. (Left) Time–activity curves illustrate radioligand dynamics at application site for intravenous, intraperitoneal, subcutaneous, and oral application. (Right) Relative systemic uptake of whole-body VOI excluding application site VOI is displayed as percentage total-body uptake. Each dot represents a mouse. Data are mean + SEM. i.p. = intraperitoneal; i.v. = intravenous; p.o. = oral; s.c. = subcutaneous. *P < 0.05 compared with intravenous application. **P < 0.01 compared with intravenous application. ***P < 0.001 compared with intravenous application.

  • FIGURE 2.
    FIGURE 2.

    In healthy mice, organ biodistribution at ≥1 h after intraperitoneal/subcutaneous radioligand application is nearly equivalent to that after intravenous injection. Healthy mice (6/group) underwent PET after intravenous, intraperitoneal, subcutaneous, and oral radioligand application at minutes 0–30 after start of PET and after 1, 2, and 4 h and were subsequently killed. Time–activity curves illustrate in vivo PET biodistribution of 68Ga-DOTATOC dynamics in VOIs at indicated times for intravenous, intraperitoneal, subcutaneous, and oral application. Data are mean + SEM. i.p. = intraperitoneal; i.v. = intravenous; p.o. = oral; s.c. = subcutaneous. *P < 0.05 compared with intravenous injection.

  • FIGURE 3.
    FIGURE 3.

    In healthy mice, organ biodistribution at ≥1 h after intraperitoneal/subcutaneous radioligand application is nearly equivalent to that after intravenous injection. Healthy mice (6/group) underwent PET after intravenous, intraperitoneal, subcutaneous, and oral radioligand application at minutes 0–30 after start of PET and after 1, 2, and 4 h and were subsequently killed. Time–activity curves illustrate in vivo PET biodistribution of 68Ga-PSMA dynamics in VOIs at indicated times for intravenous, intraperitoneal, subcutaneous, and oral application. Data are mean + SEM. i.p. = intraperitoneal; i.v. = intravenous; p.o. = oral; s.c. = subcutaneous. *P < 0.05 compared with intravenous injection. **P < 0.01 compared with intravenous injection. ***P < 0.001 compared with intravenous injection.

  • FIGURE 4.
    FIGURE 4.

    In healthy mice, organ biodistribution at ≥1 h after subcutaneous radioligand application is nearly equivalent to that after intravenous injection. Healthy mice (6/group) underwent PET scans after intravenous, intraperitoneal, subcutaneous, and oral radioligand application at minutes 0–30 after start of PET and after 1, 2, and 4 h and were subsequently killed. Time–activity curves illustrate in vivo PET biodistribution of 68Ga-FAPI dynamics in VOIs at indicated times for intravenous, intraperitoneal, subcutaneous, and oral application. Data are mean + SEM. i.p. = intraperitoneal; i.v. = intravenous; p.o. = oral; s.c. = subcutaneous. *P < 0.05 compared with intravenous injection. **P < 0.01 compared with intravenous injection.

  • FIGURE 5.
    FIGURE 5.

    Intraperitoneal/subcutaneous radioligand application increases tumor-to-liver uptake compared with intravenous injection. Mice with subcutaneous RM1-SSTR tumors (6/group) received intravenous, intraperitoneal, and subcutaneous administration of 68Ga-DOTATOC; underwent PET after 1 and 4 h; and then were killed (5 h), followed by assessment of radioactivity in organs and tumors by γ-counter. Plots show tumor-to-organ ratios after intravenous, intraperitoneal, and subcutaneous administration of 68Ga-DOTATOC. Each dot represents a mouse. Data are mean ± SEM. i.p. = intraperitoneal; i.v. = intravenous; s.c. = subcutaneous. *P < 0.05 compared with intravenous injection. **P < 0.01 compared with intravenous injection.

  • FIGURE 7.
    FIGURE 7.

    Intraperitoneal/subcutaneous radioligand application increases tumor-to-liver uptake compared with intravenous injection. Mice with subcutaneous HT-1080 tumors (6/group) received intravenous, intraperitoneal, and subcutaneous administration of 68Ga-FAPI; underwent PET after 1 and 4 h; and then were killed (5 h), followed by assessment of radioactivity in organs and tumors by γ-counter. Plots show tumor-to-organ ratios after intravenous, intraperitoneal, and subcutaneous administration of 68Ga-FAPI. Each dot represents a mouse. i.p. = intraperitoneal; i.v. = intravenous; s.c. = subcutaneous. Data are mean ± SEM.

  • FIGURE 6.
    FIGURE 6.

    Intraperitoneal/subcutaneous radioligand application increases tumor-to-liver uptake compared with intravenous injection. Mice with subcutaneous RM1-PSMA tumors (6/group) received intravenous, intraperitoneal, and subcutaneous administration of 68Ga-PSMA; underwent PET after 1 and 4 h; and then were killed (5 h), followed by assessment of radioactivity in organs and tumors by γ-counter. Plots show tumor-to-organ ratios after intravenous, intraperitoneal, and subcutaneous administration of 68Ga-PSMA. Each dot represents a mouse. Data are mean ± SEM. i.p. = intraperitoneal; i.v. = intravenous; s.c. = subcutaneous. *P < 0.05 compared with intravenous injection.

Tables

  • TABLE 1.

    Intraperitoneal/Subcutaneous Application Led to Increased or Equivalent Tumor Uptake Compared with Intravenous Injection

    P
    RadioligandIVIPSCPOIV vs. IPIV vs. SCIV vs. PO
    RM1-SSTR (68Ga-DOTATOC)
     In vivo, 1 h5.3 ± 0.69.9 ± 1.010.8 ± 1.6NA0.0124*0.0377*NA
     In vivo, 4 h4.4 ± 0.78.6 ± 1.111.1 ± 2.0NA0.0301* 0.0411*NA
     Ex vivo, 5 h2.9 ± 0.37.2 ± 1.16.5 ± 1.3NA0.0197*0.0827NA
    RM1-PSMA (68Ga-PSMA11)
     In vivo, 1 h2.9 ± 0.23.0 ± 0.62.6 ± 0.4NA0.98370.8297NA
     In vivo, 4 h2.6 ± 0.22.6 ± 0.72.9 ± 0.5NA0.99960.8289NA
     Ex vivo, 5 h3.3 ± 0.73.4 ± 0.83.9 ± 0.8NA0.99540.8343NA
    HT1080-FAP (68Ga-FAPI46)
     In vivo, 1 h1.2 ± 0.22.0 ± 0.42.2 ± 1.10.1 ± 0.030.30240.67320.0032†
     In vivo, 4 h1.0 ± 0.21.5 ± 0.31.1 ± 0.60.1 ± 0.040.45590.99110.0087†
     Ex vivo, 5 h1.0 ± 0.21.1 ± 0.11.4 ± 0.40.02 ± 0.010.98050.74460.0058†

    • * P < 0.05.

    • ↵† P < 0.01.

    • IV = intravenous; IP = intraperitoneal; SC = subcutaneous; PO = oral; NA = not applicable.

    • Data are mean %IA/g ± SEM of 6 mice per group.

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