Research ArticleBasic Science Investigations

A 99mTc-Labeled Ligand of Carbonic Anhydrase IX Selectively Targets Renal Cell Carcinoma In Vivo

Nikolaus Krall, Francesca Pretto, Martin Mattarella, Cristina Müller and Dario Neri
Journal of Nuclear Medicine June 2016, 57 (6) 943-949; DOI: https://doi.org/10.2967/jnumed.115.170514

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Structure of tumor-targeting ligand chelator conjugate 1. Targeting moiety is derived from approved antiglaucoma drug AAZ and has previously been shown to tolerate attachment to diverse payloads including fluorophores and drugs while maintaining low nanomolar affinity for CAIX. Peptidic 99mTc chelator moiety has previously been shown to be suitable for imaging applications in mice and humans. (B) Structure of negative control compound 2 lacking a CAIX-binding ligand. (C) Synthesis of the CAIX-binding ligand chelator conjugate by solid-phase peptide synthesis. Peptide backbone was constructed using standard Fmoc chemistry. Targeting ligand was installed using copper-catalyzed azide-alkyne cycloaddition. Radiolabeling was achieved with 99mTc-pertechnetate under reducing conditions. (D) Representative radiochromatogram of labeled ligand chelator conjugate 1. Please note 2 diastereomers resulting from labeling procedure (syn and anti) that can be separated chromatographically.

  • FIGURE 2.
    FIGURE 2.

    (A) Quantitative biodistribution of radiolabeled CAIX-binding ligand chelator conjugate 1 at different time points after intravenous injection (13 μg/kg, 14 nmol/kg). Ligand accumulates in tumor, reaching maximum uptake values after 3 h. Tumor-to-blood ratios are high (70:1) after 3 h already and further increase to 100:1 after 6 h. (B) Quantitative biodistribution of radiolabeled negative control compound 2 lacking CAIX-binding moiety at different time points after intravenous injection (13 μg/kg, 17 nmol/kg). Radioconjugate lacking tumor-antigen-binding moiety does not achieve a strong uptake inside tumor.

  • FIGURE 3.
    FIGURE 3.

    (A) Quantitative biodistribution analysis of radiolabeled CAIX-binding ligand chelator conjugate 1 6 h (solid fills) or 3 h (striped fills) after intravenous injection of different doses. Solid fills correspond to 2.5–65 μg/kg (28–74 nmol/kg). Striped fills correspond to 40 (45 nmol/kg) or 200 μg/kg (227 nmol/kg) of unlabeled followed after 10 min by 40 μg/kg (45 nmol/kg) of labeled conjugate. Doses of 25–65 μg/kg (28–74 nmol/kg) of labeled conjugate or 40 μg/kg (45 nmol/kg) of unlabeled followed by equal dose of labeled conjugate give excellent tumor uptake and tumor-to-organ ratios.

  • FIGURE 4.
    FIGURE 4.

    SPECT/CT scan 4 h after injection of radiolabeled 1 (10 μg/kg, 11 nmol/kg, 0.17 MBq) into a SKRC-52 xenograft–bearing mouse. Maximum-intensity projection (MIP) (A) and sagittal, coronal, and transaxial projections (B) through SKRC-52 xenograft tumor implanted on right flank. Int = intestine; Ki = kidney; Tu = tumor.

Additional Files

Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section

Keywords