Dataset Information

A Supramolecular Approach for Liver Radioembolization.

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 ?m) and (radiolabeled) Cy5 and ?-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 (control), 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 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.

SUBMITTER: Spa SJ

PROVIDER: S-EPMC5928896 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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A Supramolecular Approach for Liver Radioembolization.

Spa Silvia J SJ Welling Mick M MM van Oosterom Matthias N MN Rietbergen Daphne D D DDD Burgmans Mark C MC Verboom Willem W Huskens Jurriaan J Buckle Tessa T van Leeuwen Fijs W B FWB

Theranostics 20180323 9

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. <b>Methods:</b> The host-guest interaction between adamantane and cyclodextrin was employed in an <i>in vivo ...[more]

PMID: 29721086

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Project description:Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8-86.8) vs. 40.2 Gy (12.5-83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Project description:Treatment of oncologic disease has improved significantly in the last decades and in the future a vast majority of cancer types will continue to increase worldwide. As a result, many patients are confronted with primary liver cancers or metastatic liver disease. Surgery in liver malignancies has steeply improved and curative resections are applicable in wider settings, leading to a prolonged survival. Simultaneously, radiofrequency ablation (RFA) and liver transplantation (LTx) have been applied more commonly in oncologic settings with improving results. To minimize adverse events in treatments of liver malignancies, locoregional minimal invasive treatments have made their appearance in this field, in which radioembolization (RE) has shown promising results in recent years with few adverse events and high response rates. We discuss several other applications of RE for oncologic patients, other than its use in the palliative setting, whether or not combined with other treatments. This review is focused on the role of RE in acquiring patient eligibility for radical treatments, like surgery, RFA, and LTx. Inducing significant tumor reduction can downstage patients for resection or, through attaining stable disease, patients can stay on the LTx waiting list. Hereby, RE could make a difference between curative of palliative intent in oncologic patient management. Prior to surgery, the future remnant liver volume might be inadequate in some patients. In these patients, forming an adequate liver reserve through RE leads to prolonged survival without risking post-operative liver failure and minimizing tumor progression while inducing hypertrophy. In order to optimize results, developments in procedures surrounding RE are equally important. Predicting the remaining liver function after radical treatment and finding the right balance between maximum tumor irradiation and minimizing the chance of inducing radiation-related complications are still challenges.

Dataset Information

A Supramolecular Approach for Liver Radioembolization.

Publications

A Supramolecular Approach for Liver Radioembolization.

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