ArticlemAbs2015
High contrast tumor imaging with radio-labeled antibody Fab fragments tailored for optimized pharmacokinetics via PASylation.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 71 citations in OpenAlex.
- Site-specific trastuzumab Fab-DM1 via butelase-1 with ABD fusion for potent HER2-positive tumor control.Medical oncology (Northwood, London, England) · 2026Article
- Comprehensive Overview of Gastric Cancer Immunohistochemistry: Key Biomarkers, Advanced Detection Methods, and Perspectives.Medicina (Kaunas, Lithuania) · 2026Review
- Peptide and Protein Tags for the Half-Life Extension of Therapeutic Agents: A Review Article.The protein journal · 2026Review
- Advances in immunoPET/SPECT imaging: The role of Fab and F(ab')Acta pharmaceutica Sinica. B · 2025Review
- Development of a Clonal and High-Yield Mammalian Cell Line for the Manufacturing of a Hyperactive Human DNase I with Extended Plasma Half-Life Using PASylationPharmaceutics · 2024Article
- Siderocalin fusion proteins enable a newRSC chemical biology · 2023Article
- Exploration ofACS omega · 2023Article
- Efficient secretory production of proline/alanine/serine (PAS) biopolymers in Corynebacterium glutamicum yielding a monodisperse biological alternative to polyethylene glycol (PEG).Microbial cell factories · 2022Article
- GlycoTAIL and FlexiTAIL as Half-Life Extension Modules for Recombinant Antibody Fragments.Molecules (Basel, Switzerland) · 2022Article
- Effective rational humanization of a PASylated anti-galectin-3 Fab for the sensitive PET imaging of thyroid cancer in vivo.Scientific reports · 2021Article
- Noninvasive Evaluation of CD20 Expression UsingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- First In-Human Medical Imaging with a PASylatedNuclear medicine and molecular imaging · 2020Article
- PASylation of IL-1 receptor antagonist (IL-1Ra) retains IL-1 blockade and extends its duration in mouse urate crystal-induced peritonitis.The Journal of biological chemistry · 2020Article
- Development of a high affinity AnticalinTheranostics · 2020Article
- Enhancing bioactivity, physicochemical, and pharmacokinetic properties of a nano-sized, anti-VEGFR2 Adnectin, through PASylation technology.Scientific reports · 2019Article
- Overcoming Physiological Barriers to Nanoparticle Delivery-Are We There Yet?Frontiers in bioengineering and biotechnology · 2019Review
- Article
- The polypeptide biophysics of proline/alanine-rich sequences (PAS): Recombinant biopolymers with PEG-like properties.Biopolymers · 2018Article
- Influence of Defined Hydrophilic Blocks within Oligoaminoamide Copolymers: Compaction versus Shielding of pDNA Nanoparticles.Polymers · 2017Article
- Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies.European journal of nuclear medicine and molecular imaging · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although antigen-binding fragments (Fabs) of antibodies constitute established tracers for in vivo radiodiagnostics, their functionality is hampered by a very short circulation half-life. PASylation, the genetic fusion with a long, conformationally disordered amino acid chain comprising Pro, Ala and Ser, provides a convenient way to expand protein size and, consequently, retard renal filtration. Humanized αHER2 and αCD20 Fabs were systematically fused with 100 to 600 PAS residues and produced in E. coli. Cytofluorimetric titration analysis on tumor cell lines confirmed that antigen-binding activities of the parental antibodies were retained. The radio-iodinated PASylated Fabs were studied by positron emission tomography (PET) imaging and biodistribution analysis in mouse tumor xenograft models. While the unmodified αHER2 and αCD20 Fabs showed weak tumor uptake (0.8% and 0.2% ID/g, respectively; 24 h p.i.) tumor-associated radioactivity was boosted with increasing PAS length (up to 9 and 26-fold, respectively), approaching an optimum for Fab-PAS400. Remarkably, 6- and 5-fold higher tumor-to-blood ratios compared with the unmodified Fabs were measured in the biodistribution analysis (48 h p.i.) for αHER2 Fab-PAS100 and Fab-PAS200, respectively. These findings were confirmed by PET studies, showing high imaging contrast in line with tumor-to-blood ratios of 12.2 and 5.7 (24 h p.i.) for αHER2 Fab-PAS100 and Fab-PAS200. Even stronger tumor signals were obtained with the corresponding αCD20 Fabs, both in PET imaging and biodistribution analysis, with an uptake of 2.8% ID/g for Fab-PAS100 vs. 0.24% ID/g for the unmodified Fab. Hence, by engineering Fabs via PASylation, plasma half-life can be tailored to significantly improve tracer uptake and tumor contrast, thus optimally matching reagent/target interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.