Dataset Information

Necrosis binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate: a consequence from cyanine-labeling of small molecules.

ABSTRACT:

Background

There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor uptake, especially when labeled to smaller targeting vectors such as peptides. Here we demonstrate the effect of cyanine-mediated dead cell-binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate (800CW-TATE) and how this can be used as an advantage for fluorescence-guided surgery.

Results

Binding of 800CW-TATE could be blocked with DOTA⁰-Tyr³-octreotate (DOTA-TATE) on cultured SSTR₂-positive U2OS cells and was absent in SSTR₂ negative U2OS cells. However, strong binding was observed to dead cells, which could not be blocked with DOTA-TATE and was also present in dead SSTR₂ negative cells. No SSTR₂-mediated binding was observed in frozen tumor sections, possibly due to disruption of the cells in the process of sectioning the tissue before exposure to the contrast agent. DOTA-TATE blocking resulted in an incomplete reduction of 61.5 ± 5.8% fluorescence uptake by NCI-H69-tumors in mice. Near-infrared imaging and dead cell staining on paraffin sections from resected tumors revealed that fluorescence uptake persisted in necrotic regions upon blocking with DOTA-TATE.

Conclusion

This study shows that labeling peptides with cyanines can result in dead cell binding. This does not hamper the ultimate purpose of fluorescence-guided surgery, as necrotic tissue appears in most solid tumors. Hence, the necrosis binding can increase the overall tumor uptake. Moreover, necrotic tissue should be removed as much as possible: it cannot be salvaged, causes inflammation, and is tumorigenic. However, when performing binding experiments to cells with disrupted membrane integrity, which is routinely done with nuclear probes, this dead cell-binding can resemble non-specific binding. This study will benefit the development of fluorescent contrast agents.

SUBMITTER: Stroet MCM

PROVIDER: S-EPMC8110618 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Necrosis binding of Ac-Lys<sup>0</sup>(IRDye800CW)-Tyr<sup>3</sup>-octreotate: a consequence from cyanine-labeling of small molecules.

Stroet Marcus C M MCM Dijkstra Bianca M BM Dulfer Sebastiaan E SE Kruijff Schelto S den Dunnen Wilfred F A WFA Kruyt Frank A E FAE Groen Rob J M RJM Seimbille Yann Y Panth Kranthi M KM Mezzanotte Laura L Lowik Clemens W G M CWGM de Jong Marion M

EJNMMI research 20210510 1

<h4>Background</h4>There is a growing body of nuclear contrast agents that are repurposed for fluorescence-guided surgery. New contrast agents are obtained by substituting the radioactive tag with, or adding a fluorescent cyanine to the molecular structure of antibodies or peptides. This enables intra-operative fluorescent detection of cancerous tissue, leading to more complete tumor resection. However, these fluorescent cyanines can have a remarkable influence on pharmacokinetics and tumor upta ...[more]

PMID: 33970376

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Dataset Information

Necrosis binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate: a consequence from cyanine-labeling of small molecules.

Background

Results

Conclusion

Publications

Necrosis binding of Ac-Lys<sup>0</sup>(IRDye800CW)-Tyr<sup>3</sup>-octreotate: a consequence from cyanine-labeling of small molecules.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Necrosis binding of Ac-Lys0(IRDye800CW)-Tyr3-octreotate: a consequence from cyanine-labeling of small molecules.

Background

Results

Conclusion

Publications

Necrosis binding of Ac-Lys<sup>0</sup>(IRDye800CW)-Tyr<sup>3</sup>-octreotate: a consequence from cyanine-labeling of small molecules.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Necrosis binding of Ac-Lys⁰(IRDye800CW)-Tyr³-octreotate: a consequence from cyanine-labeling of small molecules.