Dosimetry of [(177)Lu]Lu-DOTATATE in patients with advanced midgut neuroendocrine tumors: Results from a substudy of the phase III NETTER-1 trial Journal Article
| Authors: | Bodei, L.; Cremonesi, M.; Ferrari, M.; Mittra, E. S.; Kulkarni, H. R.; Deroose, C. M.; Srirajaskanthan, R.; Ramage, J.; Grana, C. M.; Botta, F.; Weber, M. M.; Miederer, M.; Reddy, R.; Chicco, D.; Mariani, M. F.; Demange, A.; Erion, J. L.; Gericke, G.; Krenning, E. |
| Article Title: | Dosimetry of [(177)Lu]Lu-DOTATATE in patients with advanced midgut neuroendocrine tumors: Results from a substudy of the phase III NETTER-1 trial |
| Abstract: | This substudy of the phase III NETTER-1 trial evaluated [177Lu]Lu- DOTATATE (hereafter 177Lu-DOTATATE) for advanced midgut neuroendocrine tumors and aimed to assess dosimetry of a standard 4-cycle protocol and any potential relationship to toxicity. Change in tumor size by absorbed dose was an exploratory endpoint. Methods: Patients with locally advanced or metastatic, well-differentiated, midgut neuroendocrine tumors were enrolled in this substudy between August 2013 and January 2016. Patients were scheduled to receive 4 infusions of 7.4 GBq of 177Lu-DOTATATE for a cumulative injected activity of 29.6 GBq. After a 177Lu-DOTATATE infusion, whole-body planar images (4-6 time points for up to 7 d) and SPECT/CT images (at 24 and/or 48 h) were acquired, and absorbed and time-integrated activity coefficients were calculated to derive dosimetry. Blood and urine samples were used to determine the blood clearance and activity elimination rate. Tumor absorbed dose was derived using a sphere model, interpolating 177Lu dose factors on the basis of each lesion mass. Tumor size was assessed by measuring the longest and perpendicular dimensions on CT at measured time points. Results: Dosimetric assessments were evaluated in 20 patients. Organ dosimetry showed substantial interpatient variability. The predicted mean cumulative absorbed doses to kidneys and bone marrow were 19.4 (SD, 8.7) and 1.0 (SD, 0.8) Gy, respectively. Three patients had kidney doses between 28 and 33 Gy; 2 had grade 1 increased serum creatinine, and 1 showed no evidence of renal toxicity (up to 5 y of follow-up). Hematologic toxicity was primarily mild or moderate (grade 1-2) with no increase over time or association with cumulative absorbed dose. Tumor kinetics in 65 lesions demonstrated stable activity over time. Inter- and intrapatient variability was observed, and the median cumulative absorbed dose was 134 Gy (range, 7-2,218 Gy). Acknowledging the limitations of the imaging methods used and tumor volume assessments, we found no correlation between the best tumor size reduction and the absorbed dose, though most tumors (90%) shrank over the 72-wk study period. Conclusion: The dosimetry data support the findings that the standard treatment regimen with 177Lu-DOTATATE that includes personalized adjustments according to acute toxicity assessments is well tolerated and manageable. © 2025 by the Society of Nuclear Medicine andMolecular Imaging. |
| Keywords: | adult; clinical article; aged; middle aged; clinical trial; drug withdrawal; bone metastasis; follow up; prospective study; radiopharmaceuticals; image analysis; tumor volume; blood toxicity; leukopenia; radiotherapy; hemoglobin; creatinine blood level; pathology; diagnostic imaging; retrospective study; risk factor; lymphocytopenia; neuroendocrine tumor; bone lesion; karnofsky performance status; whole body imaging; kidney function; dosimetry; multicenter study; radiopharmaceutical agent; octreotide; phase 3 clinical trial; radiometry; leukocyte count; lethargy; organometallic compound; organometallic compounds; scintigraphy; creatinine clearance; neuroendocrine tumors; platelet count; stomach obstruction; ureter obstruction; plasma clearance; humans; human; male; female; article; radiopharmaceutical therapy; elimination half-life; peptide receptor radionuclide therapy; single photon emission computed tomography-computed tomography; single photon emission computed tomography computed tomography; urine sampling; generalized edema; lutetium dotatate lu 177; [<sup>177</sup>lu]lu-dotatate; advanced midgut neuroendocrine tumor |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 66 |
| Issue: | 3 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2025-03-01 |
| Start Page: | 449 |
| End Page: | 456 |
| Language: | English |
| DOI: | 10.2967/jnumed.124.268903 |
| PUBMED: | 39947918 |
| PROVIDER: | scopus |
| PMCID: | PMC11876735 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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