Hyperfractionated Treatment with 177Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model
1
Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
2
Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden
3
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(1), 235; https://doi.org/10.3390/cancers14010235
Submission received: 10 November 2021
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Revised: 29 December 2021
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Accepted: 29 December 2021
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Published: 4 January 2022
(This article belongs to the Special Issue Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development)
Simple Summary
Neuroendocrine tumors are slow growing and initially associated with vague symptoms and, therefore, often spread in the patient’s body at diagnosis, leading to a poor prognosis without means of curation through surgery. Although tumor-targeting treatments exist and are used in clinics, they are not fully optimized. The aim of this study was to test different dosages and time intervals of the radioactive pharmaceutical 177Lu-octreotate. We found that dividing a dosage into several portions and administering it at short time intervals resulted in a stronger tumor reduction and/or prolonged time for regrowth in mice than if given as a single dose. The biggest differences were seen in the lower dosage levels of the study. The findings indicate that there is clear room for improvements in the treatment of neuroendocrine tumors with 177Lu-octreotate.
Abstract
Radionuclide treatment of patients with neuroendocrine tumors has advanced in the last decades with favorable results using 177Lu-octreotate. However, the gap between the high cure rate in animal studies vs. patient studies indicates a potential to increase the curation of patients. The aim of this study was to investigate the tumor response for different fractionation schemes with 177Lu-octreotate. BALB/c mice bearing a human small-intestine neuroendocrine GOT1 tumor were either mock treated with saline or injected intravenously with a total of 30–120 MBq of 177Lu-octreotate: 1 × 30, 2 × 15, 1 × 60, 2 × 30, 1 × 120, 2 × 60, or 3 × 40 MBq. The tumor volume was measured twice per week until the end of the experiment. The mean tumor volume for mice that received 2 × 15 = 30 and 1 × 30 MBq 177Lu-octreotate was reduced by 61% and 52%, respectively. The mean tumor volume was reduced by 91% and 44% for mice that received 2 × 30 = 60 and 1 × 60 MBq 177Lu-octreotate, respectively. After 120 MBq 177Lu-octreotate, given as 1–3 fractions, the mean tumor volume was reduced by 91–97%. Multiple fractions resulted in delayed regrowth and prolonged overall survival by 20–25% for the 120 MBq groups and by 45% for lower total activities, relative to one fraction. The results indicate that fractionation and hyperfractionation of 177Lu-octreotate are beneficial for tumor reduction and prolongs the time to regrowth.
Keywords:
GEP-NET; midgut carcinoid; DOTATATE; BALB/c; somatostatin; radiopharmaceutical; radionuclide therapy; PRRT; Lutathera
