Introduction: Radiolabeled OTSA, a monoclonal antibody targeting SS developed by Oncotherapy Science, was used to treat relapsing SS metastatic patients following a theranostic procedure: in case of significant 111In-OTSA101 tumors uptake and favorable biodistribution, patient was randomly treated with 370 or 1110 MBq 90Y-OTSA101. 3D dosimetry results were compared to the observed biological toxicity.

Method: GATE was performed on repeated SPECT-CT acquisitions from H1 till H144 post-injection of 185 MBq/1.5 mg 111In-OTSA101. Volumes of interest (VOI) were drawn in normal organs on H1 CT and reported with deformable registration on following acquisitions. Quantification and residence time of 111In-OTSA101 in VOI were used for 3D absorbed dose estimation of 90Y-OTSA101 in the liver (lEAD), kidneys (kEAD), mediastinal blood pool (mbpEAD) and bone marrow (bmEAD).  Toxicity was evaluated on blood tests at D7, D14, and D28.

Results: Eight/20 included patients could be treated. One patient was even treated twice 6 months apart as disease was stabilized after the first injection of 1110 MB of 90Y-OTSA101. EAD appeared to be the highest in the liver (lEAD) (mean: 5.46 Gy[1.49-11.2]), followed by mbpEAD (mean: 1.29 Gy[0.17-4.47]), kEAD (mean: 1.53 Gy[0.25-2.62]) and then bmEAD(mean: 1.29Gy[0.17-4.47]), which was consistent with visual analysis. However, biological data demonstrated medullary toxicity in every patient but one: 6 patients with grade 3 or 4. Only one presented with transient grade 2 liver toxicity and 2 patients with transient grade 1 renal toxicity. There was no correlation between medullary toxicity and mbpEAD (r=0.54), nor bmEAD (r=0.52), nor mbpEAD +bmEAD (r=0.55). At least one related severe adverse effect was observed in 4/5 patients treated with 1110 MBq and 1/3 patients treated with 370 MBq.

Conclusion: 3D dosimetry failed to predict biological toxicity in patients treated with 90Y-OTSA101. Medullary toxicity was underestimated with the use of 111In-OTSA101 as a surrogate marker.