Quantitative 177Lu-SPECT (QSPECT) during second cycle predicts 68Ga-octreotate-PET/CT molecular response to 177Lu-octreotate PRRT

411 Objectives: Quantitative SPECT (QSPECT)/CT is increasingly used in 177Lu theranostics. Beside dosimetry, QSPECT/CT enables real-time therapeutic response assessment that is potentially predictive of longer-term response, such as molecular imaging response assessed with 68Ga-PET/CT, for which we previously proposed the Theranostic Response Criteria In Solid Tumors (THERCIST) based on molecular tumor volume (MTV). Our aim was to assess if an early decrease in total lesion fraction (TLF: total lesion activity divided by body weight, expressed in percentage of injected activity) on QSPECT during peptide receptor radionuclide therapy (PRRT) predicted an objective response on post-treatment 68Ga-PET/CT. Methods: 32 consecutive patients with neuroendocrine tumor who underwent 68Ga-octreotate-PET/CTs within 4 months prior to and after a personalized, dosimetry-based 177Lu-octreotate PRRT induction course were included. A threshold of 25% of the SUVpeak was used for tumor segmentation. The 177Lu-QSPECT/CTs performed 3 days after the first and second 177Lu-octreotate administrations were compared. An early response was defined as a decrease in TLF of 30% or more. Pre- and post-PRRT 68Ga-PET/CTs were compared according to THERCIST: CMR (complete molecular response): disappearance of all lesions; PMR (partial molecular response): ≥50% decrease in tumor burden; SMD (stable molecular disease): <50% variation in tumor burden; PMD (progressive molecular disease): ≥50% increase in tumor burden. Late PET response was correlated to early QSPECT response, and the predictive performance of the latter was assessed. Results: 10 (31%) patients were identified as early responders and 22 (69%) as non-early responders based on QSPECT. The final PET molecular imaging outcome was PMR in 9 (28%) and non-PMR in 23 patients (72%; SMD in 21 and PMD in 2). The late PET response was significantly correlated with the early QSPECT response (Figure; r=0.56, P=0.0009). An early response on QSPECT predicted a PMR with a sensitivity, specificity, positive and negative predictive values and accuracy of 67%, 83%, 60%, 86% and 78%, respectively (P=0.0126). An early QSPECT response at cycle 2, i.e. only 2 mo. after PRRT initiation, conferred a likelihood ratio of 3.8 to obtain a PMR after the induction course completion. Of note, 19 (83%) of patients who failed to demonstrate an early decrease in TLF did not experience a PMR (17 SMD; 2 PMD). Conclusion: QSPECT response 2 mo. after PRRT initiation is an early predictor of objective response to PRRT. As such, early QSPECT response represents a novel imaging biomarker of radiosensitivity and tumor biology, which could be useful to prospectively tailor a precision PRRT regimen, e.g. treatment escalation to maximize debulking or de-escalation to avoid toxicity, in radiosensitive and radioresistant neuroendocrine tumors, respectively. Research Support: Scholarship from Fonds de recherche du Quebec - Sante to JMB.