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Pharmacokinetics and PET imaging properties of two recombinant anti‐PSMA antibody fragments in comparison to their parental antibody
Author(s) -
Wiehr Stefan,
Bühler Patrick,
Gierschner Dorothee,
Wolf Philipp,
Rolle AnnaMaria,
Kesenheimer Christian,
Pichler Bernd J.,
ElsässerBeile Ursula
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22794
Subject(s) - biodistribution , monoclonal antibody , antibody , in vivo , recombinant dna , dota , in vitro , prostate cancer , ex vivo , chemistry , positron emission tomography , imaging agent , microbiology and biotechnology , radioimmunotherapy , cancer research , pathology , medicine , nuclear medicine , cancer , immunology , biology , biochemistry , gene
BACKGROUND Radioimmunoimaging with disease‐specific tracers can be advantageous compared to that with nonspecific tracers for the imaging of glucose metabolism and cell proliferation. Monoclonal antibodies (mAbs) or their fragments are excellent tools for immuno‐positron emission tomography (PET). In this study, PSMA‐specific mAb 3/F11 and its recombinant fragments were compared for the imaging of prostate cancer in xenografts. METHODS Recombinant anti‐PSMA antibody fragments D7‐Fc and D7‐CH3 were constructed by genetically fusing the binding domains of mAb 3/F11 (D7) to the human IgG3 CH3 or CH2–CH3 (Fc) domain. The fragments and the mAb 3/F11 were DOTA conjugated, tested in vitro, and radiolabeled with 64 Cu. PSMA‐positive C4‐2 and PSMA‐negative DU 145 prostate cancer xenografts were used for PET‐MR imaging and for ex vivo biodistribution. RESULTS The constructs showed strong and specific binding to PSMA‐positive C4‐2 cells in vitro which did not decrease after DOTA conjugation. Both tested fragments showed stable accumulation in PSMA‐positive C4‐2 tumors at all measured time points but reduced uptake compared to the full‐length antibody. Other organs and PSMA‐negative tumors showed a very low tracer uptake only 3 hr after injection, with the exception of the kidneys, which demonstrated high radioactivity uptake due to rapid renal clearance of the mAb fragments. CONCLUSION Stable tumor uptake and fast serum clearance of the tested radiolabeled fragments was observed in this preclinical study compared to the full length mAb. Since the fragments show rapid and specific tumor uptake, the tested fragments might serve as tools for theranostic imaging with suitable isotopes for radioimmunotherapy. Prostate 74:743–755, 2014 . © 2014 Wiley Periodicals, Inc.