Three-dimensional Monte Carlo-based voxel-wise tumor dosimetry in patients with neuroendocrine tumors who underwent 177 Lu-DOTATOC therapy.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Springer Japan Country of Publication: Japan NLM ID: 8913398 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1864-6433 (Electronic) Linking ISSN: 09147187 NLM ISO Abbreviation: Ann Nucl Med Subsets: MEDLINE
    • Publication Information:
      Publication: Tokyo, Japan : Springer Japan
      Original Publication: Tokyo, Japan : Japanese Society of Nuclear Medicine, [1987-
    • Subject Terms:
      Antineoplastic Agents/*pharmacokinetics ; Lutetium/*pharmacokinetics ; Neuroendocrine Tumors/*radiotherapy ; Octreotide/*analogs & derivatives ; Organometallic Compounds/*pharmacology ; Radioisotopes/*pharmacokinetics ; Radiopharmaceuticals/*pharmacokinetics; Aged ; Antineoplastic Agents/administration & dosage ; Chromogranin A/radiation effects ; Female ; Humans ; Lutetium/administration & dosage ; Male ; Middle Aged ; Monte Carlo Method ; Octreotide/administration & dosage ; Octreotide/chemistry ; Octreotide/pharmacokinetics ; Organometallic Compounds/administration & dosage ; Organometallic Compounds/pharmacokinetics ; Radioisotopes/administration & dosage ; Radiometry ; Radiopharmaceuticals/administration & dosage ; Radiotherapy Dosage ; Single Photon Emission Computed Tomography Computed Tomography ; Treatment Outcome
    • Abstract:
      Background: Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for 177 Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD).
      Methods: A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of 177 Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes.
      Results: The average dose values per cycle were 3.41 ± 1.28 Gy (1.91-6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14-11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47-39.49 Gy) for all 177 Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1-2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p =  < 0.05). The pre-therapeutic chromogranin A (CgA) value and the TTD correlated significantly (Pearson correlation:  = 0.67, p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy.
      Conclusion: These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.
    • References:
      Lancet. 2016 Mar 5;387(10022):968-977. (PMID: 26703889)
      J Clin Oncol. 2008 Jun 20;26(18):3063-72. (PMID: 18565894)
      Ann Oncol. 2013 Jan;24(1):152-60. (PMID: 22967994)
      J Clin Oncol. 2008 May 1;26(13):2124-30. (PMID: 18445841)
      Z Med Phys. 2020 May;30(2):116-134. (PMID: 31859029)
      Comput Biol Med. 2013 Jun;43(5):559-67. (PMID: 23485201)
      Ann Surg Oncol. 2010 Sep;17(9):2427-43. (PMID: 20217257)
      J Nucl Med. 2015 Feb;56(2):177-82. (PMID: 25593115)
      N Engl J Med. 2014 Jul 17;371(3):224-33. (PMID: 25014687)
      Cancer. 2001 Sep 1;92(5):1101-7. (PMID: 11571721)
      J Endocrinol. 1995 Jan;144(1):49-59. (PMID: 7891024)
      Pancreas. 2010 Aug;39(6):707-12. (PMID: 20664470)
      Eur J Nucl Med Mol Imaging. 2011 Dec;38(12):2125-35. (PMID: 21892623)
      J Nucl Med. 2006 Sep;47(9):1467-75. (PMID: 16954555)
      Dig Liver Dis. 2010 Mar;42(3):220-5. (PMID: 19819769)
      Recent Results Cancer Res. 2013;194:551-9. (PMID: 22918782)
      Eur J Nucl Med Mol Imaging. 2018 Feb;45(2):262-277. (PMID: 28894897)
      Mol Imaging Biol. 2015 Aug;17(4):585-93. (PMID: 25475521)
      J Clin Endocrinol Metab. 1989 Oct;69(4):902-5. (PMID: 2778040)
      Eur J Nucl Med Mol Imaging. 2003 Jun;30(6):917-20. (PMID: 12677301)
      Neuroendocrinology. 2012;95(2):157-76. (PMID: 22262022)
      Eur J Nucl Med Mol Imaging. 2010 Feb;37(2):212-25. (PMID: 19727718)
      Endocr Relat Cancer. 2017 May;24(5):243-251. (PMID: 28320783)
      Nucl Med Commun. 2016 Oct;37(10):1030-7. (PMID: 27243215)
      Neuroendocrinology. 2017 Apr 13;105(3):295-309. (PMID: 28402980)
      Recent Results Cancer Res. 2013;194:519-36. (PMID: 22918780)
      Eur J Nucl Med Mol Imaging. 2018 Jun;45(6):923-930. (PMID: 29387927)
      Cancer Treat Rev. 2013 May;39(3):270-4. (PMID: 22819619)
      Phys Med Biol. 2017 Oct 03;62(20):7959-7980. (PMID: 28854159)
      Cancer Biother Radiopharm. 2007 Jun;22(3):406-16. (PMID: 17651048)
      N Engl J Med. 2017 Jan 12;376(2):125-135. (PMID: 28076709)
      Cancer. 2010 Feb 15;116(4 Suppl):1084-92. (PMID: 20127957)
      Ann Nucl Med. 2019 Jul;33(7):521-531. (PMID: 31119607)
      J Clin Oncol. 2011 Mar 1;29(7):934-43. (PMID: 21263089)
      Eur J Nucl Med Mol Imaging. 2006 Nov;33(11):1346-51. (PMID: 16847654)
      Biomed Res Int. 2013;2013:935351. (PMID: 23865075)
      J Clin Oncol. 2009 Oct 1;27(28):4656-63. (PMID: 19704057)
    • Contributed Indexing:
      Keywords: 177Lu-DOTATOC; Dosimetry; Monte Carlo simulations; Neuroendocrine tumors
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Chromogranin A)
      0 (Organometallic Compounds)
      0 (Radioisotopes)
      0 (Radiopharmaceuticals)
      5H0DOZ21UJ (Lutetium)
      BRH40Y9V1Q (Lutetium-177)
      RGO812Q0C8 (edotreotide lutetium LU-177)
      RWM8CCW8GP (Octreotide)
      U194AS08HZ (Edotreotide)
    • Publication Date:
      Date Created: 20200302 Date Completed: 20210112 Latest Revision: 20210202
    • Publication Date:
      20221213
    • Accession Number:
      PMC7101301
    • Accession Number:
      10.1007/s12149-020-01440-3
    • Accession Number:
      32114682