SSTR-directed radiopharmaceutical therapy in a patient with small cell lung cancer: an intrapatient comparison of SSTR-agonist and antagonist

Somatostatin receptor (SSTR) overexpression has been described for a subgroup of small cell lung cancer (SCLC). SSTR-directed radiopharmaceutical therapy (RPT) with well-established SSTR-agonists and newer SSTR-antagonists could offer a further therapeutic option for this devastating disease. The aim of this study is to compare therapeutic efficacy and dosimetry of SSTR-agonist and SSTR-antagonist RPT in a patient with SCLC. We present an intrapatient dosimetric comparison between the SSTR-agonist [ 177 Lu]Lu-HA-DOTATATE and the SSTR-antagonist [ 177 Lu]Lu-SSO110 in a heavily pretreated 64-year-old male with advanced SCLC. The patient received six cycles of [ 177 Lu]Lu-HA-DOTATATE followed by one cycle of [ 177 Lu]Lu-SSO110. Multi-time-point post-therapy SPECT/CT dosimetry was performed for cycles 2 (HA-DOTATATE) and 7 (SSO-110), and single-time-point dosimetry for the remaining cycles of [ 177 Lu]Lu-HA-DOTATATE. A maintained or even increased absorbed dose coefficient (ADC) was observed from the application of [ 177 Lu]Lu-SSO110, although the patient had been treated by six cycles of [ 177 Lu]Lu-HA-DOTATATE, indicating a sustained receptor binding despite prior SSTR-directed RPT with an SSTR-agonist. ADCs for kidneys (0.58 vs. 0.4 Gy/GBq), liver (0.28 vs. 0.32 Gy/GBq), and lungs (0.58 vs. 0.36 Gy/GBq) were comparable between agonist and antagonist cycles. Given the limitations of the study and that it only comprises a single patient, both [ 177 Lu]Lu-HA-DOTATATE and [ 177 Lu]Lu-SSO110 demonstrated similar biodistribution and dosimetry in this heavily pretreated patient. Even after six cycles of SSTR-directed RPT, lesion uptake of [ 177 Lu]Lu-SSO110 was preserved and should be evaluated in further studies. • Intrapatient dosimetric comparison between the SSTR-agonist [ 177 Lu]Lu-HA-DOTATATE and the SSTR-antagonist [ 177 Lu]Lu-SSO110 in heavily pretreated advanced small cell lung cancer. • [ 177 Lu]Lu-HA-DOTATATE and [ 177 Lu]Lu-SSO110 demonstrated comparable biodistribution and dosimetry. • Even after six cycles of SSTR directed RPT, lesion uptake of [ 177 Lu]Lu-SSO110 was preserved and may indicate a higher efficacy and ongoing therapeutic effect of the SSTR-antagonist [ 177 Lu]Lu-SSO110 compared to the SSTR agonist [ 177 Lu]Lu-HA-DOTATATE.