Preliminary results of the Phase 1 Lip-Re I clinical trial: biodistribution and dosimetry assessments in hepatocellular carcinoma patients treated with Re-SSS Lipiodol radioembolization.

Purpose: This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of Re-188-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 Re-188-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72h 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 Re-188-SSS Lipiodol was 1645 +/- 361MBq. 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 Re-188-SSS Lipiodol administered was detected in serum samples at 6h, declining rapidly thereafter. On average, 1.5 +/- 1.6% of administered activity was eliminated in urine and feces over 72h. 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 +/- 1.2 Gy to the lungs. Four patients had stable disease on CT scans at 2months. 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: Re-188-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.