<i>In vivo</i> demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system

Leonidova, Anna; Foerster, Christian; Zarschler, Kristof; Schubert, M.; Pietzsch, Hans‐Jürgen; Steinbach, Jörg; Bergmann, Ralf; Metzler‐Nolte, Nils; Stephan, Holger; Gasser, Gilles

doi:10.1039/c5sc00951k

Cited by 38 publications

(53 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PNAs bind to complementary strands via Watson-Crick base-pairing and are thermally stable, chemically stable, nonimmunogenic, nontoxic, and resistant to digestion by both nucleases and proteases. The feasibility of PNA-mediated pretargeting was recently demonstrated using a variant of cetuximab bearing a pair of 17-mer PNAs (27). In this work, the complementary PNA strand was PEGylated, modified with a 2,2-dipicolylamine chelator, and labeled with 99m Tc.…”

Section: Approach 3: Oligonucleotidesmentioning

confidence: 99%

Pretargeted Imaging and Therapy

et al. 2017

View full text Add to dashboard Cite

In vivo pretargeting stands as a promising approach to harnessing the exquisite tumor-targeting properties of antibodies for nuclear imaging and therapy while simultaneously skirting their pharmacokinetic limitations. The core premise of pretargeting lies in administering the targeting vector and radioisotope separately and having the 2 components combine within the body. In this manner, pretargeting strategies decrease the circulation time of the radioactivity, reduce the uptake of the radionuclide in healthy nontarget tissues, and facilitate the use of short-lived radionuclides that would otherwise be incompatible with antibody-based vectors. In this short review, we seek to provide a brief yet informative survey of the 4 preeminent mechanistic approaches to pretargeting, strategies predicated on streptavidin and biotin, bispecific antibodies, complementary oligonucleotides, and bioorthogonal click chemistry.

show abstract

Section: Approach 3: Oligonucleotidesmentioning

confidence: 99%

Pretargeted Imaging and Therapy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…36 We recently described active tumour pretargeting with PNA bioconjugates as complementary system. More specifically, we modified on one hand epidermal growth factor receptor (EGFR) 37 It is worth highlighting that PEGylation of complementary effector PNAs led to an increased blood residence time without substantially influencing their hybridisation properties. Furthermore, these PNA conjugates rapidly cleared from the body via the kidneys and already 1 h postinjection, radioactivity was mostly detected in the kidneys and bladder (Fig.…”

Section: Recognition Systems Based On In Vivo Hybridisation Of Synthementioning

confidence: 99%

New insights into the pretargeting approach to image and treat tumours

et al. 2016

Self Cite

View full text Add to dashboard Cite

Tumour pretargeting is a promising strategy for cancer diagnosis and therapy allowing for the rational use of long circulating, highly specific monoclonal antibodies (mAbs) for both non-invasive cancer radioimmunodetection (RID) and radioimmunotherapy (RIT). In contrast to conventional RID/RIT where the radionuclides and oncotropic vector molecules are delivered as presynthesised radioimmunoconjugates, the pretargeting approach is a multistep procedure that temporarily separates targeting of certain tumour-associated antigens from delivery of diagnostic or therapeutic radionuclides. In principle, unlabelled, highly tumour antigen specific mAb conjugates are, in a first step, administered into a patient. After injection, sufficient time is allowed for blood circulation, accumulation at the tumour site and subsequent elimination of excess mAb conjugates from the body. The small fast-clearing radiolabelled effector molecules with a complementary functionality directed to the prelocalised mAb conjugates are then administered in a second step. Due to its fast pharmacokinetics, the small effector molecules reach the malignant tissue quickly and bind the local mAb conjugates. Thereby, corresponding radioimmunoconjugates are formed in vivo and, consequently, radiation doses are deposited mainly locally. This procedure results in a much higher tumour/non-tumour (T/NT) ratio and is favourable for cancer diagnosis and therapy as it substantially minimises the radiation damage to non-tumour cells of healthy tissues. The pretargeting approach utilises specific non-covalent interactions (e.g. strept(avidin)/biotin) or covalent bond formations (e.g. inverse electron demand Diels-Alder reaction) between the tumour bound antibody and radiolabelled small molecules. This tutorial review descriptively presents this complex strategy, addresses the historical as well as recent preclinical and clinical advances and discusses the advantages and disadvantages of different available variations.

show abstract

“…Thanks to these characteristics, PNAs are very promising for several applications ranging from nanotechnology 41,42 to in vivo antisense therapy 43 and tumour pre-targeting. 8 However, there is room for improvement of the potential of PNAs in biological applications, for example by increasing their low solubility in physiological environment or by equipping them with a probe for cellular localization. It is therefore important to develop techniques for PNA functionalization.…”

Section: Pna Functionalization With Photoclickmentioning

confidence: 99%

“…to therapeutic/diagnostic metal-based drugs can, for example, increase their organ/cell selectivity. [6][7][8][9][10] In a similar vein, the insertion of metal fragments into biologically active molecules can yield biocompatible and extremely useful tools for biological investigations, such as luminescent probes. 11 The application of copper-catalyzed azide-alkyne cycloaddition (CuAAC, commonly referred to as click chemistry) for bioconjugation has been extensively exploited due to the high versatility, selectivity and functional group tolerance of this synthetic technique.…”

Section: Introductionmentioning

confidence: 99%