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            <title xml:lang="en">[90Y]Y-L4-Lipo/ ethyl esters of Iodized fatty acids of poppy seed oil (lipiodol® ultra-fluid), a new TARE formulation, designed from a lipophilic ligand for stability and safety</title>
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            <funder>This study was supported by Guerbet. The Center for Microscopy and Molecular Imaging (CMMI) is supported by the European Regional Development Fund (ERDF) and the Walloon Region. GVS, GD, CDM and NP were supported in addition by the Fondation ULB, the Fonds Erasme and “Association Vinçotte Nuclear” (AVN). NL acknowledges support by Labex IRON (grant no. ANR-11-LABX-0018).</funder>
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                <title xml:lang="en">[90Y]Y-L4-Lipo/ ethyl esters of Iodized fatty acids of poppy seed oil (lipiodol® ultra-fluid), a new TARE formulation, designed from a lipophilic ligand for stability and safety</title>
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                    <forename type="first">Gaëtan</forename>
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                    <forename type="first">Elisabeth</forename>
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                    <forename type="first">Nicolas</forename>
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                    <forename type="first">Olivier</forename>
                    <surname>Rousseaux</surname>
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                <term xml:lang="en">Yttrium-90</term>
                <term xml:lang="en">Transarterial radioembolization (TARE)</term>
                <term xml:lang="en">Lipiodol® Ultra-Fluid</term>
                <term xml:lang="en">Hepatocellular carcinoma (HCC)</term>
                <term xml:lang="en">Hepatocellular carcinoma</term>
                <term xml:lang="en">Biology</term>
                <term xml:lang="en">Internal medicine</term>
                <term xml:lang="en">Receptor</term>
                <term xml:lang="en">Botany</term>
                <term xml:lang="en">Medicine</term>
                <term xml:lang="en">Biochemistry</term>
                <term xml:lang="en">Chromatography</term>
                <term xml:lang="en">Iodized oil</term>
                <term xml:lang="en">Ligand (biochemistry)</term>
                <term xml:lang="en">Chemistry</term>
                <term xml:lang="en">Poppy</term>
                <term xml:lang="en">Lipiodol</term>
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              <p>Background: Despite recent therapeutic advances, managing liver cancer remains a significant medical and economic priority for many countries. Patients often present at an advanced stage, preventing them from benefiting from salvage surgery. Consequently, palliative treatments play a crucial role in managing these cancers. Interventional radiology techniques are well-known for providing significant benefits to patients. [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid is a novel transarterial radioembolization formulation designed for selective arterial injection to deliver localized radiation treatment of advanced unresectable liver tumors. This study aimed to confirm the stability of [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid, investigate its biodistribution in an animal model, and conduct an initial dosimetry evaluation.Results: Less than 3% of 90Y was released from the [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid formulation in human serum. The tumor-to-liver activity ratio (T/NT) expressed in %ID/g tissue at 1 h, 24 h, 3 days, and 6 days (5.50 ± 2.42, 3.28 ± 1.94, 4.89 ± 3.41 and 4.77 ± 1.59, respectively) suggests effective targeting of tumor tissue compared to healthy liver tissue. The extrapolated absorbed doses in Gy in humans to the tumor, normal liver, lung, and red marrow per GBq of [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid administered were 54.3, 16.2, 0.69 and 0.89, for males, and 54.3, 22.3, 0.84 and 0.89, respectively, for females.Conclusion: With good in vitro stability at low activity lasting at least 3 half-lives and a T/NT ratio of 4 in vivo, [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid is confirmed as a valid candidate treatment for transarterial radioembolization of hepatocellular carcinoma. High activity stability in both in vitro and in vivo studies is needed to complete the formulation's safety profile.</p>
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