{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:11:27Z","timestamp":1760058687720,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and\/or metastatic well-differentiated NETs. Before the approval of Lutathera\u00ae, locally manufactured 177Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was (1) to compare the hematotoxicity of locally manufactured 177Lu-HA-DOTATATE with Lutathera\u00ae in GEP-NET patients and (2) to compare the recommended treatment interval of 8 weeks between each cycle to a prolonged scheme of up to 11 weeks for both 177Lu-HA-DOTATATE and Lutathera\u00ae. Methods: The included patients with GEP NETs (n = 46) received four cycles of PRRT, either 177Lu-HA-DOTATATE or Lutathera\u00ae, and were divided into four subgroups. The subgroups were treated with either locally manufactured 177Lu-HA-DOTATATE or Lutathera\u00ae and were stratified into a mean application interval of 8 (HA8weeks, n = 10\/Lutathera8weeks, n = 16) or 11 weeks (HAadapted, n = 10\/Lutatheraadapted, n = 10). To evaluate therapy associated hemato- and nephrotoxicity, patients underwent two laboratory follow-up examinations (follow-up 1\u2014between 2.\/3. therapy cycle; follow-up 2\u2014after the termination of the 4. therapy cycle) and were then compared to pre-PRRT laboratory results. To assess hematological and renal recovery trends, blood values and parameters of kidney function were collected up to 58.9 weeks after PRRT completion. Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) were used for grading hematological parameters. Results: The occurrence of high-grade adverse events (CTCAE grade 3\/4) after PRRT was moderate, with 1\/10 (10%) grade 4 lymphocytopenia in the Lutatheraadapted group, while overall, 20\/46 (43.5%) patients had grade 3 lymphocytopenia. Grade 3 thrombocytopenia occurred in 1\/10 (10%) patients of the HAadapted group. Absolute and percentage changes in the kidney function (creatinine, TER) remained constant during PRRT in all subgroups. All four subgroups showed a significant decrease in absolute blood value changes for PLT counts, WBC counts, neutrophil granulocytes and lymphocytes between, prior to and after PRRT (p &lt; 0.05, each). Regarding percentage changes in laboratory parameters, only the HAadapted and the HA8weeks groups had significant decreases in WBC (p &lt; 0.03, each) and PLT counts (p &lt; 0.04, each) while there was no significant degradation of any other hematological parameter in any of the subgroups. Only patients with longer treatment intervals under 177Lu-HA-DOTATATE therapy showed a statistically significant correlation in the long-term recovery analysis concerning the PLT counts (r = 0.6, p &lt; 0.0001). Other blood and kidney values showed no significant correlation in the long-term analysis in the other subgroups. Conclusion: Comparing the hematotoxicity in patients that were treated with locally manufactured 177Lu-HA-DOTATATE with patients that were treated with Lutathera\u00ae and assessing different treatment intervals in both groups (8 vs. 11 weeks), revealed that there is overall a low to moderate incidence of significant changes in hematological and renal parameters directly after PRRT. Recovery trends of hematological and renal parameters after 1 year suggest that patients treated with locally manufactured 177Lu-HA-DOTATATE might benefit from a longer treatment interval of 11 weeks regarding their PLT counts. Given the risk of developing hematological diseases such as therapy-related myeloid neoplasms years after PRRT, longer observational periods after PRRT will be crucial.<\/jats:p>","DOI":"10.3390\/cancers17091423","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:18:02Z","timestamp":1745475482000},"page":"1423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of the Hematotoxicity of PRRT with Lutathera\u00ae and Locally Manufactured 177Lu-HA-DOTATATE in Patients with Neuroendocrine Tumors and the Impact of Different Application Intervals"],"prefix":"10.3390","volume":"17","author":[{"given":"Markus","family":"Hofmann","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3175-952X","authenticated-orcid":false,"given":"Sophie C.","family":"Kunte","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), Partner Site Munich, 80539 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Unterrainer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Die Radiologie, 80331 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Delker","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrien","family":"Holzgreve","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Nuclear Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Toms","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz Joseph","family":"Gildehaus","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-3722","authenticated-orcid":false,"given":"Christoph J.","family":"Auernhammer","sequence":"additional","affiliation":[{"name":"ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Internal Medicine 4, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Spitzweg","sequence":"additional","affiliation":[{"name":"ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Department of Internal Medicine 4, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias J.","family":"Zacherl","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harun","family":"Ilhan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Die Radiologie, 80331 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-5662","authenticated-orcid":false,"given":"Johannes","family":"R\u00fcbenthaler","sequence":"additional","affiliation":[{"name":"Department of Radiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonie","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena M.","family":"Unterrainer","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, LMU University Hospital, LMU Munich, 81377 Munich, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), Partner Site Munich, 80539 Munich, Germany"},{"name":"Department of Nuclear Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1002\/ijc.30400","article-title":"The epidemiology of metastases in neuroendocrine tumors","volume":"139","author":"Hemminki","year":"2016","journal-title":"Int. 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