Predictive accuracy of pre-therapy I-123-NaI dosimetry for patients treated with I-131-NaI as part of the UK multi-centre SELIMETRY trial

Abstract

Aim/Introduction: The aim of the UK-based multi-centre clinical trial SELIMETRY (EudraCT No 2015-002269-47) is to investigate the potential use of the MEK 1/2 inhibitor, Selumetinib (AZD6244, ARRY-142886), to re-sensitise patients with iodine refractory differentiated thyroid cancer to radioiodine therapy. Lesion biokinetic analysis is performed both for the pre-treatment 123I-NaI and for the subsequent 131I-NaI therapy. The aim of this study was to evaluate the potential for the 123I-NaI study to predict the biokinetics following the therapeutic administration. Materials and Methods: Pre-treatment dosimetry involved up to five SPECT/CT scans at 5, 24, 30, 48 and 72 hours after a 370 MBq 123I-NaI administration following four weeks of Selumetinib therapy. Four post-therapy SPECT/ CT scans were performed at 24, 48, 72 and 144 hours following radioiodine therapy with 5.5 GBq of 131I-NaI. rhTSH stimulation was used before 123I-NaI scans and 131I-NaI therapy. The SPECT scans were quantified using system calibration factors [1]. Activity retention in lesions was determined from large VOIs placed on the SPECT scans to include spill-out due to the partial-volume effect. Activity in the large VOIs was corrected for background activity. Lesions were outlined on the CT scans by a trained radiologist to obtain lesion volumes. Absorbed doses were calculated using the MIRD formalism. Uncertainties in the absorbed doses were estimated using recent EANM guidance. Pearson product-moment correlation coefficients were computed to assess relationships between results from pretreatment and post-therapy dosimetry. Results: Preliminary results obtained for 10 lesions (lesion size range: 0.4 - 42 .3 ml), in 3 patients treated as part of the clinical trial suggest a strong, positive correlation between predicted activity retention at 24 hours from the pre-treatment dosimetry and measured activity retention post-therapy (r=0.98, n=10, p<0.001). Predicted and measured activity retention at 24 hours after administration agreed in the majority of cases (8/10) within the associated uncertainties. Furthermore, a strong, positive correlation between predicted and measured effective half-lives of activity retention in lesions assuming a single exponential decay was found (r=0.96, n=10, p<0.001). Conclusion: Preliminary results suggest that the lesion biokinetics of pre-treatment 123I-NaI are applicable to subsequent 131I-NaI therapy of advanced thyroid cancer. This will potentially allow for a more personalised approach in the treatment of patients with metastatic thyroid cancer based on patient-specific dosimetry.