177Lu-DOTATATE ile Tedavi Edilen Nöroendokrin Tümörlü Hastalarda Renal Dozimetri ve Nefrotoksisite Değerlendirmesi

Öz

Amaç: Bu çalışmanın amacı, nöroendokrin tümör tanısı almış 22 hastada, 5550 MBq (150 mCi) 177Lu-DOTATATE radyofarmasötik uygulaması sonrasında hesaplanan böbrek dozları ve glomerüler filtrasyon hızlarına (GFR) dayalı olarak dozimetri yapmak ve renal toksisiteyi değerlendirmektir. Materyal ve Metod: 35 ile 80 yaşları arasında, 14 erkek ve 8 kadından oluşan hastalar, lezyonları belirlemek için 68Ga-DOTATATE PET/CT taramaları geçirmiş ve ardından tedavi planlaması yapılmıştır. 177Lu-DOTATATE tüm vücut görüntüleme kullanılarak dozimetri, uygulamadan 4, 24, 48 ve 72 saat sonra gerçekleştirilmiştir. Bulgular: Sonuçlarımıza göre, ortalama tedavi döngüsü sayısı 5±1, ortalama toplam böbrek dozu 24.32±3.5 (Gy), ortalama toplam BED dozu 27.9±2.5 (Gy), ortalama tüm vücut dozu 1.83±0.4 (Gy) ve ortalama GFR 69.95±12.2 olarak bulunmuştur. Böbrek dozları ile GFR arasındaki korelasyon R²=0.7945 olarak hesaplanmıştır. Toplam böbrek dozları ile toplam böbrek BED dozları arasındaki ilişkinin önemi Mann-Whitney U testi kullanılarak değerlendirilmiştir (p=0.0244). Sonuç: Çalışma, tedavi döngüsü sayısı arttıkça toplam böbrek dozunun da arttığını; ancak GFR'de hızlı düşüşlerin gözlemlenmediğini ve tedavi edilen hastaların hiçbirinin böbreklerde toksik dozlara ulaşmadığını bulmuştur.

Anahtar Kelimeler

• MIRD metodu
• 68Ga DOTATATE
• 177Lu DOTATATE
• nöroendokrin tümör
• radyonüklit dozimetri

Assessment of Renal Dosimetry and Nephrotoxicity in Patients with Neuroendocrine Tumors Treated with 177Lu-DOTATATE

Öz

Aim: This study aimed to conduct dosimetry and evaluate renal toxicity based on calculated kidney doses and glomerular filtration rates (GFR) in 22 patients diagnosed with neuroendocrine tumors following the administration of 5550 MBq (150 mCi) of 177Lu-DOTATATE radiopharmaceutical. Materials and Methods: Patients, aged between 35 and 80, including 14 males and 8 females, underwent 68Ga-DOTATATE PET/CT scans to identify lesions and subsequently received treatment planning. Dosimetry of ¹⁷⁷Lu-DOTATATE was performed using whole-body imaging based on scans acquired at 4, 24, 48, and 72 hours post-administration. Results: According to our results, the average number of treatment cycles was 5±1, with an average total kidney dose of 24.32±3.5 (Gy), average total BED dose of 27.9±2.5 (Gy), average whole-body dose of 1.83±0.4 (Gy), and average GFR of 69.95±12.2. The correlation between kidney doses and GFR was calculated as R2=0.7945. The significance of the relationship between total kidney doses and total kidney BED doses was evaluated using the Mann-Whitney U test (p=0.0244). Conclusion: The study found that as the number of treatment cycles increased, the total kidney dose also increased; however, rapid declines in GFR were not observed, and none of the treated patients reached toxic doses in the kidneys.

Anahtar Kelimeler

• MIRD method
• 68Ga-DOTATATE
• 177Lu-DOTATATE
• neuroendocrine tumor
• radionuclide dosimetry

Kaynakça

1. 1. Kwekkeboom DJ, de Herder WW, van Eijck CH, Kam BL, van Essen M, Teunissen JJ. Eric P. Krenning , Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010; 40:78–88.
2. 2. Melis M, Krenning EP, Bernard BF, Barone R, Visser TJ, de Jong M. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues. Eur J Nucl Med Mol Imaging 2005 ;32:1136– 43.
3. 3. Erik S. Mittra Neuroendocrine Tumor Therapy:177Lu-DOTATATE American Roentgen Ray Society 2018.
4. 4. Svensson J, Berg G, Wängberg B, Larsson M, Forssell-Aronsson E, Bernhardt P, Renal function affects absorbed dose to the kidneys and haematological toxicity during 177Lu-DOTATATE treatment. Eur. J. Nucl. Med. Mol. Imaging 2015; 42:947–55.
5. 5. Sandström M, Garske-Román U, Johansson S, Granberg D, Sundin A, Freedman N. Kidney dosimetry during 177Lu-DOTATATE therapy in patients with neuroendocrine tumors: aspects on calculation and tolerance. Acta Oncologica 2017; 57(4):516-21.
6. 6. Gupta SK, Singla S, Bal C. Renal and hematological toxicity in patients of neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-DOTATATE. Cancer Biother Radiopharm 2012; 27:593–9.
7. 7. Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, Brill AB. MIRD pamphlet No. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. Journal of Nuclear Medicine 1999; 40(2):37-61.
8. 8. Wessels BW, Konijnenberg MW, Dale RG, Breitz HB, Cremonesi M, Meredith RF, Thomas SR. MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response implications for radionuclide therapy. Journal of Nuclear Medicine 2008; 49(11):1884-9.

9. 9. Stabin MG, Konijnenberg MW. Re-evaluation of absorbed fractions for photons and electrons in spheres of various sizes. Journal of nuclear medicine 2000; 41(1):149-60.
10. 10. Sandström M, Freedman N, Fröss-Baron K, Kahn T, Sundin A. Kidney dosimetry in 777 patients during 177Lu-DOTATATE therapy: aspects on extrapolations and measurement time points, EJNMMI Physics 2020; 7(1):73.
11. 11. Sundlöv A, Sjögreen-Gleisner K, Svensson J, Ljungberg M, Olsson T, Bernhardt P, Tennvall J. Individualised 177 Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry. European journal of nuclear medicine and molecular imaging 2017; 44:1480-9.
12. 12. Delker A, Ilhan H, Zach C, Brosch J, Gildehaus FJ, Lehner S, Bartenstein P, Böning G. The influence of early measurements onto the estimated kidney dose in [(177)Lu][DOTA(0), Tyr(3)]Octreotate Peptide receptor radiotherapy of neuroendocrine tumors. Mol Imaging Biol 2015; 17(5):726–34.
13. 13. King M, Farncombe T. An overview of attenuation and scatter correction of planar and SPECT data for dosimetry studies. Cancer Biother Radiopharm 2003; 18:181–90.
14. 14. Knoll P, Rahmim A, Gültekin S, Šámal M, Ljungberg M, Mirzaei S. Szczupak B. Improved scatter correction with factor analysis for planar and SPECT imaging. Review of Scientific Instruments 2017; 88(9).
15. 15. Ilan E, Sandström M, Wassberg C, Sundin A, Garske-Román U, Eriksson B, Lubbering M. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE. J Nucl Med 2015; 56(2):177–82.
16. 16. Hänscheid H, Lapa C, Buck AK, Lassmann M, Werner RA. Dose Mapping after endoradiotherapy with 177Lu-DOTATATE/DOTATOC by a single measurement after 4 days. J Nucl Med 2018; 59(1):75–81.
17. 17. Nautiyal A, Michopoulou S, Guy M. Dosimetry in Lu-177-DOTATATE peptide receptor radionuclide therapy: a systematic review. Clinical and Translational Imaging 2024, 12(2): 157-75.
18. 18. Sandström M, Ilan E, Karlberg A, Johansson S, Freedman N, Garske-Román U, Method dependence,observer variability and kidney volumes in radiation dosimetry of(177)Lu-DOTATATE therapy in patients with neuroendocrine tumours. EJNMMI Phys 2015; 2:24.
19. 19. Ilan E, Sandstrom M, Wassberg C, Wassberg C, Sundin A, Garske–Román U, Eriksson B, Granberg D and Lubberink M. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE. J Nucl Med 2015; 56:177–82.
20. 20. Garske U, Sandström M, Johansson S, Granberg D, Lundqvist H, Lubberink M, Eriksson B. Lessons on tumour response: Imaging during therapy with 177Lu-DOTA-octreotate. A case report on a patient with a large volume of poorly differentiated neuroendocrine carcinoma. Theranostics 2012; 2(5):459.
21. 21. Gustafsson J, Brolin G, Cox M, Ljungberg M, Johansson L & Gleisner KS Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy. Physics in Medicine & Biology 2015; 60(21): 8329.