[Article] Absorbed Dose–Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine

Absorbed Dose–Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine

Kevin Hebert1, Lore Santoro1,2, Maeva Monnier3, Florence Castan3, Ikrame Berkane1, Eric Assenat4, Cyril Fersing1–5, Pauline Gelibert6, Jean-Pierre Pouget2, Manuel Bardies1,2 , Pierre-Olivier Kotzki1,2 , and Emmanuel Deshayes1,2 
1  Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université  de Montpellier, Montpellier, France;
2 Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France;
3 Biometry Unit, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France;
4 Department of Medical Oncology, CHU de Montpellier, Universiteé de Montpellier, Montpellier, France;
5 IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France; and 6Centre Hospitalier Métropole Savoie, Chambéry, France


Introduction: [177Lu]Lu-DOTATATE has been approved for progressive and inoper-able gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigra-phy measurements of the g-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treat-ment efficacy (tumor shrinkage and survival) and toxicity.


Methods: Patient with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measure-ment masked to the somatostatin receptor imaging uptake). For toxic-ity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients’ health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models.

Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1–9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor vol-ume variation (P , 0.001) 3mo after treatment end, and it was a signifi-cant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not corre-lated with nephrotoxicity during the studied period.

Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influenc-ing clinical management.