A supramolecular approach for liver radioembolization

Silvia J. Spa, Mick M. Welling, Matthias N. van Oosterom, Daphne D.D. Rietbergen, Mark C. Burgmans, Willem Verboom, Jurriaan Huskens, Tessa Buckle, Fijs W.B. van Leeuwen* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Abstract

Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.

Original languageEnglish
Pages (from-to)2377-2386
Number of pages10
JournalTheranostics
Volume8
Issue number9
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Adamantane
Cyclodextrins
Liver
Lung
Nanotechnology
Therapeutics
Confocal Microscopy
Radioisotopes
Intravenous Administration
Polymers

Keywords

  • Nanotechnology
  • Pre-targeting
  • Radioembolization
  • Supramolecular chemistry
  • Interventional radiology

Cite this

Spa, S. J., Welling, M. M., van Oosterom, M. N., Rietbergen, D. D. D., Burgmans, M. C., Verboom, W., ... van Leeuwen, F. W. B. (2018). A supramolecular approach for liver radioembolization. Theranostics, 8(9), 2377-2386. https://doi.org/10.7150/thno.23567
Spa, Silvia J. ; Welling, Mick M. ; van Oosterom, Matthias N. ; Rietbergen, Daphne D.D. ; Burgmans, Mark C. ; Verboom, Willem ; Huskens, Jurriaan ; Buckle, Tessa ; van Leeuwen, Fijs W.B. / A supramolecular approach for liver radioembolization. In: Theranostics. 2018 ; Vol. 8, No. 9. pp. 2377-2386.
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abstract = "Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 {\%}ID/g and 10.5 {\%}ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.",
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Spa, SJ, Welling, MM, van Oosterom, MN, Rietbergen, DDD, Burgmans, MC, Verboom, W, Huskens, J, Buckle, T & van Leeuwen, FWB 2018, 'A supramolecular approach for liver radioembolization', Theranostics, vol. 8, no. 9, pp. 2377-2386. https://doi.org/10.7150/thno.23567

A supramolecular approach for liver radioembolization. / Spa, Silvia J.; Welling, Mick M.; van Oosterom, Matthias N.; Rietbergen, Daphne D.D.; Burgmans, Mark C.; Verboom, Willem; Huskens, Jurriaan; Buckle, Tessa; van Leeuwen, Fijs W.B. (Corresponding Author).

In: Theranostics, Vol. 8, No. 9, 01.01.2018, p. 2377-2386.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A supramolecular approach for liver radioembolization

AU - Spa, Silvia J.

AU - Welling, Mick M.

AU - van Oosterom, Matthias N.

AU - Rietbergen, Daphne D.D.

AU - Burgmans, Mark C.

AU - Verboom, Willem

AU - Huskens, Jurriaan

AU - Buckle, Tessa

AU - van Leeuwen, Fijs W.B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.

AB - Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.

KW - Nanotechnology

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KW - Radioembolization

KW - Supramolecular chemistry

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Spa SJ, Welling MM, van Oosterom MN, Rietbergen DDD, Burgmans MC, Verboom W et al. A supramolecular approach for liver radioembolization. Theranostics. 2018 Jan 1;8(9):2377-2386. https://doi.org/10.7150/thno.23567