The Foundation Dedicated to Discovering a Cure for Neuroendocrine Cancer

Caring for Carcinoid Foundation

Peptide Receptor Radionuclide Therapy (PRRT)

Peptide Receptor Radionuclide Therapy (PRRT)

Most neuroendocrine tumors, including carcinoid, have five highly specialized receptors that bind to the naturally occurring hormone somatostatin.Octreotide is a synthetic analogue (a man-made version) of somatostatin that is able to attach to two of these five somatostatin receptors. 

Peptide receptor radionuclide therapy (PRRT) combines octreotide with a radionuclide (a radioactive substance) to form highly specialized molecules called radiolabeled somatostatin analogues or radiopeptides.  These radiopeptides can be injected into a patient and will travel throughout the body binding to carcinoid tumor cells that have receptors for them. Once bound, these radiopeptides emit radiation and kill the tumor cells they are bound to. 

There are three radionuclides that are attached to octreotide to create radiopeptides: indium 111 (111In), yttrium 90 (90Y) and lutetium 177 (177Lu).  These radiopeptides differ in the type of radiation they emit as well as the depth of tissue into which they penetrate.  Tissue penetration is an important factor since a certain range of radiation is necessary to kill tumor cells but not damage surrounding, healthy tissues. 111In emits both Auger electrons and γ-radiation and has the shortest range of tissue penetration (10 µm), 90Y emits β-radiation and has a range of 12 mm, and 177Lu emits both β-radiation and γ-radiation and has a range of 2 mm (Kwekkeboom, de Herder, van Eijck,  Kam, van Essen, Teunissen, Krenning, 2010).

Studies have shown that in certain individuals, the short-term results of PRRT with 177Lu and 90Y (and 111In  to a much lesser degree) are: a decrease in tumor size, a decrease in symptoms, and a halt in tumor progression (Bushnell, O’Dorisio, O’Dorisio, Menda, Hicks, Van Cutsem, Baulieu, Borson-Chazot, Anthony, Benson, Oberg, Grossman, Connolly, Bouterfa, Li, Kacena, LaFrance, & Pauwels, 2010).

Common side-effects of radiopeptide therapy are nausea, vomiting and abdominal pain.  Other less common side-effects are bone, liver and kidney toxicity, and mild hair loss. (Bushnell et al., 2010).

Individuals whose tumors can be visualized by somatostatin receptor scintigraphy (SRS) or 68 GA –DOTATE PET/CT (Haug,  Auernhammer, Wangler, Schmidt, Uebleis, Goke, Cumming, Bartenstein, Tiling, &  Hacker, 2010) and have inoperable carcinoid tumors that are growing or individuals whose symptoms are not well managed by somatostatin analogues may be candidates for PRRT. However, the extent of tumor growth, kidney function, liver function, prior treatments, and many other factors must also be considered.  (Bushnell et al., 2010; Haug et al, 2010).

For more information on peptide receptor radiotherapy please consider:

  • Video from a Carcinoid Neuroendocrine Tumor Society Singapore meeting- Neuroendocrine Tumors: Diagnosis & Treatment w/ Peptide Receptor Radiotherapy(PRRT) by Dr. Richard Baum Part 1 and Part 2.
  • CFCF Expert Interview with Dr. Baum and CFCF Director of Patient Support, Ben Blackwood.  In the interview Dr. Baum describes his experience in treating patients at the Neuroendocrine Tumor Clinic at Bad Berka where over 1,000 patients are treated annually.  Please click here to listen to this interview. 

References

Akerstrom, G., Hellman, P., Hessman, O., and Osmak, L. (2005). Management of midgut carcinoids. Journal of Surgical Oncology, 1(89), 161-169. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/15719373.

Blonski, W., Reddy, K., Shaked, A., Siegelman, E., Metz, D. (2005) Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature. World Journal of Gastroenterology, 11(48), 7676-7683. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/16437698.

Borch, K., Ahren, B., Ahlman, H., Falkmer, S., Granerus, G., Grimelius, L., (2005). Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Annals of Surgery, 242(1), 64-73. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/15973103.

Bushnell, D., O’Dorisio, T., O’Dorisio, M., Menda, Y., Hicks, R., Van Cutsem, E., Baulieu, J., Borson-Chazot, F., Anthony, L., Benson, A., Oberg, K., Grossman, A., Connolly, M., Bouterfa, H., Li, Y., Kacena, K., LaFrance, N., Pauwels, S. (2010). 90Y-edotreotide for metastatic carcinoid refractory to octreotide. Journal of Clinical Oncology, 28(10), 1652-1659. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/20194865.

Chan, J., Kulke, M. (2009). Progress in the treatment of neuroendocrine tumors. Current Oncology Reports, 11(3), 193-199. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/19336011

Chughtai, T., Morin, J., Sheiner, N., Wilson, J., Mulder, D. (1997). Bronchial carcinoid—twenty years’ experience defines a selective surgical approach.Surgery, 22(4), 801-808. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/9347859.

Fiala, P., Petraskova, K., Cernohorsky, S., Kinkor, Z., Krepela, E., Zatloukal, P. (2003) Bronchial carcinoid tumors: long-term outcome after surgery.Neoplasma, 50(1), 60-65. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/12687280.

Haug, A., Auernhammer, C., Wangler, B. Schmidt, G., Uebleis, C., Goke, B., Cumming, P., Bartenstein, P., Tiling, R., and Hacker, M. (2010). 68GA-DOTATTATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differetiated neuroendocrine tumors. Journal of Nuclear Medicine, 51(9), 1349-1356. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/20720050.

Janson E., Holmberg, L., Stridsberg, M., Eriksson, B., Theodorsson, E., Wilander, E. and Oberg, K. (1997). Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Annals of Oncology, 8(7), 685-690. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/9296223.

Kianmanesh, R., Sauvanet, A., Hentic, O., Couvelard, A., Levy, P., Vilgrain, V., Rusziewski, P., Belghiti, J. (2008). Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors : a safe approach for radical resection. Annals of Surgery, 247(4), 659-665. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/18362629.

Kulke, M. H. (2007). Clinical Presentation and Management of Carcinoid Tumors. Hematology/Oncology Clinics of North America, 21, 433-455. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/17548033.

Kwekkeboom, D., de Herder, W., van Eijck, C., Kam, B., van Essen, M., Teunissen, J., Krenning, E. (2010). Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Seminars in Nuclear Medicine, 40(2), 78-88. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/20113677.

Modlin, I., Lye, K., Kidd, M. (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer, 97(4), 934-959. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/12569593.

Norton, J., Kivlen, M., Li, M., Schneider, D., Chuter, T., and Jensen, R. (2003). Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Archives of Surgery, 138(8), 859-866. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/12912744.

Norton, J., Warren, R., Kelly, M., Zuraek, M., Jensen, R. (2003). Aggressive surgery for metastatic liver neuroendocrine tumors. Surgery, 134(6), 1057-1063. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/14668741.

Norton, J. (2005). Endocrine tumours of the gastrointestinal tract. Surgical treatment of neuroendocrine metastases. Best Practice and Research. Clinical Gastroenterology, 19(4), 577-583. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/16183528.

Oberg, K. E., Reubi, J. C., Kwekkeboom, D. J., Krenning, E. P. (2010) Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology, 139(3), 742-753. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/20637207.

Poncet, G., Faucheron, J., and Walter, T. (2010). Recent trends in the treatment of well-differentiated endocrine carcinoma o the small bowel. World Journal of Gastroenterology, 16(14), 1696-1706. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/20380000.

Ramage, J., Ahmed, A., Ardill, J., Bax, N., Breen, D.J, Caplin, M.E., Corrie, P., Davar, J., Davies, A.H., Lewington, V., Meyer, T., Newell-Price, J., Poston, G., Reed, N., Rockall, A., Steward, W., Thakker, R.V., Toubanakis, C., Valle, J., Verbeke, C., and Grossman, A.B., and UK and Ireland Neuroendocrine Tumor Society (2012) . Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut, 61(1):6-32. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/22052063

Reidy, D. L., Tang, L. H., Saltz, L. B.  (2009). Treatment of advanced disease in patients with well-differentiated neuroendocrine tumors.  Nature Clinical Practice, Oncology, 6(3), 143-152. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/19190591

Reubi, J., Kvolz, L., Waser, B., Nagorney, D., Heitz, P., Chaboneau, J., Reading, C., Moertel, C. (1990). Detection of somatostatin receptors in surgical percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Research, 50(18), 5969-5977. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/2168286.

Rinke, A., Muller, H., Schade-Brittinger, C., Lose, J., Barth, P., Weid, M., Mayer, C., Aminossadati, B., Pape, U., Blacker, M., Harder, J., Arnold, C., Gress, T., Arnold, R., PROMID Study Group. (2009). 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: a report from the PROMID Study Group. Journal of Clinical Oncology, 27(28), 4656-4663. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/19704057.

Saxena, A., Chua, T., Bester, L., Kokandi, A., Morris, D. (2010). Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumor liver metastases: a critical appraisal of 48 cases. Annals of Surgery, 251(5), 910-916. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/20395859.

Steinmuller, T., Kianmanesh, R., Falconi, M., Scarpa, A., Taal, B., Kwekkeboom, D., Lopes, J., Perren, A., Nikou, G., Yao, J., Dell Fave, G., O’Toole, D., Frascati Consensus Conference participants. (2008). Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology, 87(1), 47-62. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/18097131/.

Toumpanakis, C., Meyer, T., Caplin, M. (2007) Cytotoxic treatment including embolization/chemoembolization for neuroendocrine tumours. Best Practice and Research, Clinical Endocrinology and Metabolism, 21(1), 131-144. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/17382269.

van Vilsteren, F., Baskin-Bey, E., Nagorney, D., Sanderson, S., Kremers, W., Rosen, C., Gores, G., Hobday, T. (2006). Liver transplantation for gasteroenteropancreatic neuroendocrine cancers: Defining selection criteria to improve survival. Liver Transplantation, 12(3), 448-456. Retrieved from:http://www.ncbi.nlm.nih.gov/pubmed/16498656.

Vignot, S., Faivre, S., Aguirre, D., Raymond, E. (2005). mTOR-targeted therapy of cancer with rapamycin derivatives. Annals of Oncology, 16(4), 525-537. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/15728109