Research ArticleBasic Science Investigation

Albumin-Binding and Conventional PSMA Ligands in Combination with 161Tb: Biodistribution, Dosimetry, and Preclinical Therapy

Viviane J. Tschan, Sarah D. Busslinger, Peter Bernhardt, Pascal V. Grundler, Jan Rijn Zeevaart, Ulli Köster, Nicholas P. van der Meulen, Roger Schibli and Cristina Müller
Journal of Nuclear Medicine October 2023, 64 (10) 1625-1631; DOI: https://doi.org/10.2967/jnumed.123.265524

Article Figures & Data

Figures

  • Figure
  • FIGURE 1.
    FIGURE 1.

    (A) Cell uptake and internalization of [161Tb]Tb/[177Lu]Lu-SibuDAB and [161Tb]Tb/[177Lu]Lu-PSMA-I&T in PC-3 PIP cells after 4 h of incubation (average ± SD). (B and C) In vitro albumin-binding curves of [161Tb]Tb/[177Lu]Lu-SibuDAB and [161Tb]Tb/[177Lu]Lu-PSMA-I&T in mouse (B) and human (C) blood plasma. Dashed line indicates half-maximum (i.e., 50%) binding. HSA = human serum albumin; Int. = internalization; MSA = mouse serum albumin; Up. = uptake. *Data were previously published (27). †Data were previously published (28).

  • FIGURE 2.
    FIGURE 2.

    (A) Blood clearance of [161Tb]Tb-SibuDAB and [177Lu]Lu-SibuDAB over 24 h after injection. (B) Decay-corrected biodistribution data 4 and 24 h after injection of [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T. PC-3 flu = PSMA-negative tumor xenografts; PC-3 PIP = PSMA-positive tumor xenograft. *Data were previously published (27).

  • FIGURE 3.
    FIGURE 3.

    Dual-isotope SPECT/CT images of mice bearing PC-3 PIP (right shoulder) and PC-3 flu (left shoulder) tumor xenografts 1 and 4 h after injection of 1:1 mixture (20 MBq per mouse) of [161Tb]Tb-SibuDAB and [177Lu]Lu-SibuDAB (A) or [161Tb]Tb-PSMA-I&T and [177Lu]Lu-PSMA-I&T (B). Image reconstruction was based on γ-lines of 161Tb (red), 177Lu (green), or both (red/green overlay). Bl = bladder; Ki = kidneys; PC-3 flu = PSMA-negative tumor xenograft; PC-3 PIP = PSMA-positive tumor xenograft.

  • FIGURE 4.
    FIGURE 4.

    (A and B) Relative tumor growth curves shown until first mouse of respective group reached endpoint. (C and D) Kaplan–Meier plot (vertical offset was applied to improve readability). Mice received vehicle or were treated with [161Tb]Tb-SibuDAB or [177Lu]Lu-SibuDAB (A and C) or with [161Tb]Tb-PSMA-I&T or [177Lu]Lu-PSMA-I&T (B and D). (Data of control group and mice treated with 5 MBq and 10 MBq of [177Lu]Lu-SibuDAB were previously published (27,28).)

  • FIGURE 5.
    FIGURE 5.

    (A) Blood plasma parameters: blood urea nitrogen, albumin, and alkaline phosphatase. (B) Blood cell counts of leukocytes, erythrocytes, and thrombocytes. *Data were previously published (28).

Tables

  • TABLE 1.

    Parameters Indicative of Efficacy of Treatment

    TreatmentInjected activity (MBq)First mouse euthanized (d)*Last mouse euthanized (d)*Median survival (d)Mice alive on day 56AUCRTV
    Saline†—1428180/12477 ± 148
    [161Tb]Tb-SibuDAB2255632.51/6233 ± 111
    [177Lu]Lu-SibuDAB22256231/6306 ± 172
    [161Tb]Tb-SibuDAB55656>>56‡6/629 ± 16
    [177Lu]Lu-SibuDAB†54956>>56‡5/650 ± 50
    [161Tb]Tb-SibuDAB105656>>56‡6/620 ± 5
    [177Lu]Lu-SibuDAB§105656>>56‡6/618 ± 8
    [161Tb]Tb-PSMA-I&T5245643.53/6147 ± 134
    [177Lu]Lu-PSMA-I&T51841280/6356 ± 177
    [161Tb]Tb-PSMA-I&T104856>>56‡4/649 ± 42
    [177Lu]Lu-PSMA-I&T102856432/6108 ± 81

    • ↵* All mice that did not reach endpoint were euthanized on day 56.

    • ↵† Data were previously published (27).

    • ↵‡ Exact median survival could not be defined, since more than half of mice survived until study end (day 56).

    • ↵§ Data were previously published (28).

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