Journal
THERANOSTICS
Volume 8, Issue 9, Pages 2377-2386Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.23567
Keywords
Nanotechnology; Interventional radiology; Pre-targeting; Supramolecular chemistry; Radioembolization
Categories
Funding
- European Research Council (ERC) under the European Union's Seventh Framework Program FP7 [2012-306890]
- Netherlands Organization for Scientific Research (NWO) [STW 11435, STW BGT11272]
- Postdoctoral Molecular Imaging Scholar Program Grant - Society of Nuclear Medicine and Molecular Imaging (SNMMI)
- Education and Research Foundation (ERF) for Nuclear Medicine and Molecular Imaging
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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 mu m) and (radiolabeled) Cy5 and beta-cyclodextrin (host)-containing PIBMA polymers (Tc-99m-Cy5(0.5)CD(10)PIBMA(39); MW similar to 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (Tc-99m)-MAA-Ad or (Tc-99m)-MAA (control), the utility of the pre-targeting concept was evaluated after intravenous administration of Tc-99m-Cy5(0.5)CD(10)PIBMA(39). Results: Interactions between MAA-Ad and Cy5(0.5)CD(10)PIBMA(39) 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 Tc-99m-Cy5(0.5)CD(10)PIBMA(39) in these 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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