Kostas Delaunay1,2, Julien Edeline2,3,4, Yan Rolland5,6, Nicolas Lepareur4,7, Sophie Laffont1, Xavier Palard1,2, Christelle Bouvry7, Samuel Le Sourd3, Marc Pracht3, Valérie Ardisson7, Nicolas Noiret8, Éric Bellissant2,9,10, Etienne Garin11,12,13. 1. Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Avenue de la Bataille Flandres-Dunkerque, CS 44229, 35042, Rennes, cedex, France. 2. University of Rennes 1, Rennes, France. 3. Department of Medical Oncology, Cancer Institute Eugène Marquis, Rennes, France. 4. INSERM INRA UMR 1241 NuMeCan, University of Rennes 1, Rennes, France. 5. Department of Medical Imaging, Cancer Institute Eugène Marquis, Rennes, France. 6. INSERM UMR 1099 LTSI, University of Rennes 1, Rennes, France. 7. Radiopharmacy, Cancer Institute Eugène Marquis, Rennes, France. 8. ENSCR, CNRS, ISCR [(Institut des Sciences Chimiques de Rennes)] - UMR 6226, University of Rennes, F-35000, Rennes, France. 9. INSERM CIC 1414 Clinical Investigation Center, Rennes, France. 10. Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmaco-epidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. 11. Department of Nuclear Medicine, Cancer Institute Eugène Marquis, Avenue de la Bataille Flandres-Dunkerque, CS 44229, 35042, Rennes, cedex, France. e.garin@rennes.unicancer.fr. 12. University of Rennes 1, Rennes, France. e.garin@rennes.unicancer.fr. 13. INSERM INRA UMR 1241 NuMeCan, University of Rennes 1, Rennes, France. e.garin@rennes.unicancer.fr.
Abstract
PURPOSE: This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of 188Re-SSS Lipiodol on hepatocellular carcinoma patients included in the Phase I Lip-Re 1 study. METHODS: Results of the first six patients included are reported. Analysis of the 188Re-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72 h post-administration. Quantification in blood, urine, and stool samples was performed. Determination of the tumour to non-tumour uptake ratio (T/NT) was calculated. Absorbed doses to target organs and tumours were evaluated using the MIRD formalism. RESULTS: The mean injected activity of 188Re-SSS Lipiodol was 1645 ± 361 MBq. Uptakes were seen in the liver (tumour and healthy liver) and the lungs only. All these uptakes were stable over time. A mean 1.4 ± 0.7% of 188Re-SSS Lipiodol administered was detected in serum samples at 6 h, declining rapidly thereafter. On average, 1.5 ± 1.6% of administered activity was eliminated in urine and feces over 72 h. Overall, 90.7 ± 1.6% of detected activity on SPECT studies was found in the liver (74.9 ± 1.8% in tumours and 19.1 ± 1.7% in the healthy liver) and 9.3 ± 1.6% in the lungs (5.7 ± 1.1% in right and 3.7 ± 0.5% in left lungs). Mean doses absorbed were 7.9 ± 3.7Gy to the whole liver, 42.7 ± 34.0Gy to the tumours, 10.2 ± 3.7Gy to the healthy liver, and 1.5 ± 1.2Gy to the lungs. Four patients had stable disease on CT scans at 2 months. The first patient with rapidly progressive disease died at 1 month, most probably of massive tumour progression. Due to this early death and using a conservative approach, the trial independent evaluation committee decided to consider this event as a treatment-related toxicity. CONCLUSION: 188Re-SSS Lipiodol has a favorable biodistribution profile concerning radioembolization, with the highest in-vivo stability among all radiolabeled Lipiodol compounds reported to date. These preliminary results must be further confirmed while completing this Phase I Lip Re1 study.
PURPOSE: This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of 188Re-SSS Lipiodol on hepatocellular carcinomapatients included in the Phase I Lip-Re 1 study. METHODS: Results of the first six patients included are reported. Analysis of the 188Re-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72 h post-administration. Quantification in blood, urine, and stool samples was performed. Determination of the tumour to non-tumour uptake ratio (T/NT) was calculated. Absorbed doses to target organs and tumours were evaluated using the MIRD formalism. RESULTS: The mean injected activity of 188Re-SSS Lipiodol was 1645 ± 361 MBq. Uptakes were seen in the liver (tumour and healthy liver) and the lungs only. All these uptakes were stable over time. A mean 1.4 ± 0.7% of 188Re-SSS Lipiodol administered was detected in serum samples at 6 h, declining rapidly thereafter. On average, 1.5 ± 1.6% of administered activity was eliminated in urine and feces over 72 h. Overall, 90.7 ± 1.6% of detected activity on SPECT studies was found in the liver (74.9 ± 1.8% in tumours and 19.1 ± 1.7% in the healthy liver) and 9.3 ± 1.6% in the lungs (5.7 ± 1.1% in right and 3.7 ± 0.5% in left lungs). Mean doses absorbed were 7.9 ± 3.7Gy to the whole liver, 42.7 ± 34.0Gy to the tumours, 10.2 ± 3.7Gy to the healthy liver, and 1.5 ± 1.2Gy to the lungs. Four patients had stable disease on CT scans at 2 months. The first patient with rapidly progressive disease died at 1 month, most probably of massive tumour progression. Due to this early death and using a conservative approach, the trial independent evaluation committee decided to consider this event as a treatment-related toxicity. CONCLUSION:188Re-SSS Lipiodol has a favorable biodistribution profile concerning radioembolization, with the highest in-vivo stability among all radiolabeled Lipiodol compounds reported to date. These preliminary results must be further confirmed while completing this Phase I Lip Re1 study.
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