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Does treatment with somatostatin analogs differ in the uptake of normal target organs and malignant lesions on 68Ga-DOTATATE PET/CT imaging?

Year 2022, Volume: 32 Issue: 4, 464 - 468, 31.08.2022
https://doi.org/10.54005/geneltip.1157941

Abstract

Abstract
Objective:
Somatostatin analogs (SSA) are used in treating low-grade neuroendocrine tumors, mainly because of their antiproliferative effect. 68Ga tetraazacyclododecantetraacetic acid-DPhe1-Tyr3-octreotate (DOTATATE) PET/CT as somatostatin receptor imaging has been widely used in recent years. However, there are conflicting publications in the literature, although there are guidelines for discontinuing the use of SSA before imaging. This study aims to investigate the effect of SSAs on Somatostatin receptor imaging.
Material and Method: We retrospectively analyzed 253 patients who underwent 68Ga-DOTATATE PET/CT imaging between 2018 and 2022. Among these patients, those with low grades (Grade 1 and Grade 2) using SSA were included in the study. SUVmax (maximum standard uptake volume) of normal target organs, primary tumors, and metastases with the highest SUVmax in each organ were compared before and after SSA treatment.
Results: 28 patients (16 females; 12 males, age [mean±SD], 54.82±14.27, range 18-78) with low-grade (Grade 1 and 2) NET and 68Ga-DOTATATE PET/CT imaging with SSA therapy were included in the study. Although SUVmax was decreased in the values measured after SSA application in the liver and spleen, it was not statistically significant (p>0.05). There was no significant difference between SUVmax values in primary tumors and metastatic lesions in the liver, bone, lung, or lymph nodes before and after SSA application (P> 0.05).
Conclusion: In conclusion, these drugs do not need to be discontinued before 68Ga-DOTATATE PET/CT imaging for treatment follow-up in neuroendocrine tumor patients using somatostatin analogs. In addition, these drugs may help report interpretation by increasing the intensity of metastatic lesions in the liver and spleen.

References

  • 1. Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. European journal of nuclear medicine and molecular imaging. 2017;44(9):1588-601.
  • 2. Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, et al. 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2016;57(6):872-8.
  • 3. Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES. The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging. 2014;4(5):426-34.
  • 4. Rinke A, Wittenberg M, Schade-Brittinger C, Aminossadati B, Ronicke E, Gress TM, et al. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival. Neuroendocrinology. 2017;104(1):26-32.
  • 5. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA. EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Endocr Pract. 2016;22(9):1068-80.
  • 6. Lesche S, Lehmann D, Nagel F, Schmid HA, Schulz S. Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. The Journal of clinical endocrinology and metabolism. 2009;94(2):654-61.
  • 7. Cescato R, Schulz S, Waser B, Eltschinger V, Rivier JE, Wester HJ, et al. Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2006;47(3):502-11.
  • 8. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. European journal of nuclear medicine and molecular imaging. 2010;37(10):2004-10.
  • 9. Janson ET, Kälkner KM, Eriksson B, Westlin JE, Oberg K. Somatostatin receptor scintigraphy during treatment with lanreotide in patients with neuroendocrine tumors. Nucl Med Biol. 1999;26(8):877-82.
  • 10. Coura-Filho GB, Hoff A, Duarte PS, Buchpiguel CA, Josefsson A, Hobbs RF, et al. 68Ga-DOTATATE PET: temporal variation of maximum standardized uptake value in normal tissues and neuroendocrine tumours. Nuclear medicine communications. 2019;40(9):920-6.
  • 11. Zhang P, Yu J, Li J, Shen L, Li N, Zhu H, et al. Clinical and Prognostic Value of PET/CT Imaging with Combination of (68)Ga-DOTATATE and (18)F-FDG in Gastroenteropancreatic Neuroendocrine Neoplasms. Contrast Media Mol Imaging. 2018;2018:2340389.
  • 12. Liu Q, Cescato R, Dewi DA, Rivier J, Reubi JC, Schonbrunn A. Receptor signaling and endocytosis are differentially regulated by somatostatin analogs. Mol Pharmacol. 2005;68(1):90-101.
  • 13. Waser B, Tamma ML, Cescato R, Maecke HR, Reubi JC. Highly efficient in vivo agonist-induced internalization of sst2 receptors in somatostatin target tissues. J Nucl Med. 2009;50(6):936-41.
  • 14. Reubi JC, Waser B, Cescato R, Gloor B, Stettler C, Christ E. Internalized somatostatin receptor subtype 2 in neuroendocrine tumors of octreotide-treated patients. The Journal of clinical endocrinology and metabolism. 2010;95(5):2343-50.
  • 15. Ayati N, Lee ST, Zakavi R, Pathmaraj K, Al-Qatawna L, Poon A, et al. Long-Acting Somatostatin Analog Therapy Differentially Alters (68)Ga-DOTATATE Uptake in Normal Tissues Compared with Primary Tumors and Metastatic Lesions. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59(2):223-7.
  • 16. Gålne A, Almquist H, Almquist M, Hindorf C, Ohlsson T, Nordenström E, et al. A Prospective Observational Study to Evaluate the Effects of Long-Acting Somatostatin Analogs on (68)Ga-DOTATATE Uptake in Patients with Neuroendocrine Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;60(12):1717-23.
  • 17. Velikyan I, Sundin A, Sörensen J, Lubberink M, Sandström M, Garske-Román U, et al. Quantitative and qualitative intrapatient comparison of 68Ga-DOTATOC and 68Ga-DOTATATE: net uptake rate for accurate quantification. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2014;55(2):204-10.
  • 18. Cherk MH, Kong G, Hicks RJ, Hofman MS. Changes in biodistribution on (68)Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 2018;18(1):3.
  • 19. Dörr U, Räth U, Sautter-Bihl ML, Guzman G, Bach D, Adrian HJ, et al. Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med. 1993;20(5):431-3.
  • 20. Haug AR, Rominger A, Mustafa M, Auernhammer C, Göke B, Schmidt GP, et al. Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2011;52(11):1679-83.

68Ga-DOTATATE PET/BT görüntülemede somatostatin analogları ile tedavi normal hedef organların ve malign lezyonların alımında farklılık gösterir mi?

Year 2022, Volume: 32 Issue: 4, 464 - 468, 31.08.2022
https://doi.org/10.54005/geneltip.1157941

Abstract

Amaç: Somatostatin analogları (SSA), antiproliferatif etkileri nedeniyle düşük grade’li nöroendokrin tümörlerin tedavisinde kullanılır. 68Ga tetraazasiklododekantetraasetik asit-DPhe1-Tyr3-oktreotat (DOTATATE) PET/CT somatostatin reseptör görüntülemesi olarak son yıllarda yaygın olarak kullanılmaktadır. Bununla birlikte, görüntülemeden önce SSA kullanımının kesilmesine yönelik kılavuzlar olmasına rağmen, literatürde çelişkili yayınlar bulunmaktadır. Bu çalışma, SSA'ların Somatostatin reseptör görüntülemesi üzerindeki etkisini araştırmayı amaçlamaktadır.
Gereç ve Yöntem: 2018-2022 yılları arasında 68Ga-DOTATATE PET/BT görüntüleme yapılan 253 hastayı retrospektif olarak incelendi. Bu hastalardan SSA kullanan 28 düşük grade’li (Grade 1 ve Grade 2) hasta çalışmaya dahil edildi. Normal hedef organların, primer tümörlerin ve her organda en yüksek SUVmax‘ı (maksimum standart alım hacmi) olan metastazların SSA tedavisinden önce ve sonra SUVmax değerleri karşılaştırıldı.
Bulgular: SSA tedavisi ile düşük grade’li (Grade 1 ve 2) NET ve 68Ga-DOTATATE PET/BT görüntülemesi olan 28 hasta (16 kadın; 12 erkek, yaş [ortalama±SD], 54.82±14.27, range:18-78) çalışmaya dahil edildi. Karaciğer ve dalakta SSA uygulaması sonrası ölçülen değerlerde SUVmax azalmasına rağmen istatistiksel olarak anlamlı değildi (p>0.05). Primer tümörlerdeki SUVmax değerleri ile karaciğer, kemik, akciğer veya lenf nodlarındaki metastatik lezyonlarda SSA uygulaması öncesi ve sonrası arasında anlamlı fark yoktu (P> 0.05).
Sonuç: Somatostatin analogları kullanan nöroendokrin tümör hastalarında tedavi takibi için 68Ga-DOTATATE PET/BT görüntüleme öncesinde bu ilaçların mutlak kesilmesi gerekmez. Ayrıca, karaciğer ve dalaktaki metastatik lezyonların intensitesini (yoğunluğunu) dolaylı yoldan artırarak raporun yorumlanmasına katkı sağlar.

References

  • 1. Bozkurt MF, Virgolini I, Balogova S, Beheshti M, Rubello D, Decristoforo C, et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. European journal of nuclear medicine and molecular imaging. 2017;44(9):1588-601.
  • 2. Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, et al. 68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and Conventional Imaging for Pulmonary and Gastroenteropancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2016;57(6):872-8.
  • 3. Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES. The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging. 2014;4(5):426-34.
  • 4. Rinke A, Wittenberg M, Schade-Brittinger C, Aminossadati B, Ronicke E, Gress TM, et al. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival. Neuroendocrinology. 2017;104(1):26-32.
  • 5. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA. EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Endocr Pract. 2016;22(9):1068-80.
  • 6. Lesche S, Lehmann D, Nagel F, Schmid HA, Schulz S. Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. The Journal of clinical endocrinology and metabolism. 2009;94(2):654-61.
  • 7. Cescato R, Schulz S, Waser B, Eltschinger V, Rivier JE, Wester HJ, et al. Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2006;47(3):502-11.
  • 8. Virgolini I, Ambrosini V, Bomanji JB, Baum RP, Fanti S, Gabriel M, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. European journal of nuclear medicine and molecular imaging. 2010;37(10):2004-10.
  • 9. Janson ET, Kälkner KM, Eriksson B, Westlin JE, Oberg K. Somatostatin receptor scintigraphy during treatment with lanreotide in patients with neuroendocrine tumors. Nucl Med Biol. 1999;26(8):877-82.
  • 10. Coura-Filho GB, Hoff A, Duarte PS, Buchpiguel CA, Josefsson A, Hobbs RF, et al. 68Ga-DOTATATE PET: temporal variation of maximum standardized uptake value in normal tissues and neuroendocrine tumours. Nuclear medicine communications. 2019;40(9):920-6.
  • 11. Zhang P, Yu J, Li J, Shen L, Li N, Zhu H, et al. Clinical and Prognostic Value of PET/CT Imaging with Combination of (68)Ga-DOTATATE and (18)F-FDG in Gastroenteropancreatic Neuroendocrine Neoplasms. Contrast Media Mol Imaging. 2018;2018:2340389.
  • 12. Liu Q, Cescato R, Dewi DA, Rivier J, Reubi JC, Schonbrunn A. Receptor signaling and endocytosis are differentially regulated by somatostatin analogs. Mol Pharmacol. 2005;68(1):90-101.
  • 13. Waser B, Tamma ML, Cescato R, Maecke HR, Reubi JC. Highly efficient in vivo agonist-induced internalization of sst2 receptors in somatostatin target tissues. J Nucl Med. 2009;50(6):936-41.
  • 14. Reubi JC, Waser B, Cescato R, Gloor B, Stettler C, Christ E. Internalized somatostatin receptor subtype 2 in neuroendocrine tumors of octreotide-treated patients. The Journal of clinical endocrinology and metabolism. 2010;95(5):2343-50.
  • 15. Ayati N, Lee ST, Zakavi R, Pathmaraj K, Al-Qatawna L, Poon A, et al. Long-Acting Somatostatin Analog Therapy Differentially Alters (68)Ga-DOTATATE Uptake in Normal Tissues Compared with Primary Tumors and Metastatic Lesions. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;59(2):223-7.
  • 16. Gålne A, Almquist H, Almquist M, Hindorf C, Ohlsson T, Nordenström E, et al. A Prospective Observational Study to Evaluate the Effects of Long-Acting Somatostatin Analogs on (68)Ga-DOTATATE Uptake in Patients with Neuroendocrine Tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;60(12):1717-23.
  • 17. Velikyan I, Sundin A, Sörensen J, Lubberink M, Sandström M, Garske-Román U, et al. Quantitative and qualitative intrapatient comparison of 68Ga-DOTATOC and 68Ga-DOTATATE: net uptake rate for accurate quantification. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2014;55(2):204-10.
  • 18. Cherk MH, Kong G, Hicks RJ, Hofman MS. Changes in biodistribution on (68)Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 2018;18(1):3.
  • 19. Dörr U, Räth U, Sautter-Bihl ML, Guzman G, Bach D, Adrian HJ, et al. Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med. 1993;20(5):431-3.
  • 20. Haug AR, Rominger A, Mustafa M, Auernhammer C, Göke B, Schmidt GP, et al. Treatment with octreotide does not reduce tumor uptake of (68)Ga-DOTATATE as measured by PET/CT in patients with neuroendocrine tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2011;52(11):1679-83.
There are 20 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Original Article
Authors

Farise Yılmaz 0000-0001-8136-513X

Hasan Önner This is me 0000-0003-1002-2097

Gonca Kara Gedik 0000-0003-4607-8615

Özlem Şahin 0000-0001-5318-0066

Ahmet Volkan Çelik 0000-0001-8082-6643

Çağlagül Erol 0000-0001-6857-5212

Publication Date August 31, 2022
Submission Date August 8, 2022
Published in Issue Year 2022 Volume: 32 Issue: 4

Cite

Vancouver Yılmaz F, Önner H, Kara Gedik G, Şahin Ö, Çelik AV, Erol Ç. Does treatment with somatostatin analogs differ in the uptake of normal target organs and malignant lesions on 68Ga-DOTATATE PET/CT imaging?. Genel Tıp Derg. 2022;32(4):464-8.

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