Skip to main content

Radionuclide Cancer Therapy: Unsealed Alpha- and Beta-Emitters

  • Chapter
  • First Online:
Locoregional Radionuclide Cancer Therapy

Abstract

Radionuclide cancer therapy using radiopharmaceuticals may target organ-specific tumors, such as thyroid, prostate gland, bone, or lymphomas, or neuroendocrine tumors. They deliver the radiation that they carry along to the targeted organ-specific malignant lesions with an intent to cure, control, or diminish the size of the tumor or disease. Specific molecular pathways can direct targeted therapy to a specific organ or the entire body of the patient using unsealed α-, β-, and γ-emitting radionuclides. Using radiopharmaceuticals with radionuclides emitting gamma radiation for imaging and different radionuclides emitting beta radiations, or radiopharmaceuticals emitting both beta and gamma emissions, theranostic approaches may be accomplished. The current clinical uses of these radiopharmaceuticals in treating cancer are described in this chapter. Potential uses and clinical trials are also reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Bagheri MH, Ahlman MA, Lindenberg L, et al. Advances in medical imaging for the diagnosis and management of common genitourinary cancers. Urol Oncol. 2017;35(7):473–91.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pene F, Courtine E, Cariou A, Mira JP. Toward theranostics. Crit Care Med. 2009;37:S50–8.

    Article  CAS  PubMed  Google Scholar 

  3. Jeelani S, Reddy RC, Maheswaran T, Asokan GS, Dany A, Anand B. Theranostics: a treasured tailor for tomorrow. J Pharm Bioallied Sci. 2014;6(Suppl 1):S6–8. https://doi.org/10.4103/0975-7406.137249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chan IS, Ginsburg GS. Personalized medicine: progress and promise. Annu Rev Genomics Hum Genet. 2011;12:217–44. https://doi.org/10.1146/annurev-genom-082410-101446.

    Article  CAS  PubMed  Google Scholar 

  5. Sairamesh J, Michael R. An economic perspective on personalized medicine. HUGO J. 2013;7:1.

    Article  Google Scholar 

  6. Levine R, Krenning EP. Clinical history of the theranostic radionuclide approach to neuroendocrine tumors and other types of cancer: historical review based on an interview of Eric P. Krenning by Rachel Levine. J Nucl Med. 2017;58:3S–9S.

    Article  CAS  PubMed  Google Scholar 

  7. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pryma DA, Chin BB, Noto RB, et al. Efficacy and safety of high-specific-activity I-131 MIBG therapy in patients with advanced pheochromocytoma or paraganglioma. J Nucl Med. 2019;60:623–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kassis AI, Adelstein SJ. Therapeutic potential of internally administered radionuclides. In: Black PMcL, Schoene WC, Lampson LA, eds. Contemporary issues in neurological surgery. Astrocytomas: diagnosis, treatment, and biology. Special Supplement of Medical Physics on radiolabeled antibody tumor dosimetry. Med Phys. 1993;20:497.

    Google Scholar 

  10. Macklis RM, Kinsey BM, Kassis AI, Ferrara JLM, Atcher RW, Hines JJ, Coleman CN, Adelstein SJ, Burakoff SJ. Radio immunotherapy with alpha – particle-emitting immune conjugates. Science. 1988;240:1024–6.

    Article  CAS  PubMed  Google Scholar 

  11. Bayer NJ. Xofigo (radium Ra 223 dichloride) injection [prescribing information]. Bayer HealthCare Pharmaceuticals, Inc; May 2013.

    Google Scholar 

  12. Poeppel TD, Handkiewicz-Junak D, Andreeff M, et al. EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:824–45. https://doi.org/10.1007/s00259-017-3900-4.

    Article  CAS  PubMed  Google Scholar 

  13. Hoskin P, Sartor O, O’Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang MW, Aksnes A-K, Parker C. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases with or without previous docetaxel use: a pre-specified subgroup analysis from the randomized, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014;15(12):1397–406, ISSN 1470-2045.

    Article  CAS  PubMed  Google Scholar 

  14. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  15. Tu SM, Kim J, Pagliaro LC, Vakar-Lopez F, Wong FC, Wen S, General R, Podoloff DA, Lin SH, Logothetis CJ. Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy. J Clin Oncol. 2005;23(31):7904–10.

    Article  CAS  PubMed  Google Scholar 

  16. Tu SM, Mathew P, Wong FC, Jones D, Johnson MM, Logothetis CJ. Phase I study of concurrent weekly docetaxel and repeated samarium-153 lexidronam in patients with castration-resistant metastatic prostate cancer. J Clin Oncol. 2009;27(20):3319–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jain N, Wierda W, Ferrajoli A, Wong F, Lerner S, Keating MK, O’Brien S. A phase 2 study of yttrium-90 ibritumomab tiuxetan (Zevalin) in patients with chronic lymphocytic leukemia. Cancer. 2009;115(19):4533–9.

    Article  CAS  PubMed  Google Scholar 

  18. Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:2453–63.

    Article  CAS  PubMed  Google Scholar 

  19. Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood. 2000;96:1259–66.

    Article  CAS  PubMed  Google Scholar 

  20. Wahl RL. The clinical importance of dosimetry in radioimmunotherapy with tositumomab and iodine I 131 tositumomab. Semin Oncol. 2003;30(Suppl 4):31–8.

    Article  CAS  PubMed  Google Scholar 

  21. Abbatt JD. Experiences of management and treatment of polycythemia using P32 as a therapeutic weapon. J Fac Radiol. 1953;5(2):141–7.

    Article  CAS  PubMed  Google Scholar 

  22. Tennvall J, Brans B. EANM procedure guideline for 32P phosphate treatment of myeloproliferative diseases. Eur J Nucl Med Mol Immaging. 2007;34(8):1324–7.

    Article  Google Scholar 

  23. Papotti M, Bongiovanni M, Volante M, et al. Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch. 2002;440:461–75.

    Article  CAS  PubMed  Google Scholar 

  24. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123ITyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med. 1993;20:716–31.

    Article  CAS  PubMed  Google Scholar 

  25. Limouris GS, Dimitropoulos N, Kontogeorgakos D, et al. Evaluation of the therapeutic response to 111In-DTPA-octreotide based targeted therapy in liver metastatic neuroendocrine tumors according to CT/MRI/US findings. Can Bio Rad. 2005;20(2):215–7.

    CAS  Google Scholar 

  26. Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol. 2001;12:941–5.

    Article  CAS  PubMed  Google Scholar 

  27. Dromain C, Déandréis D, Scoazec JY, et al. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging. 2016;97:1241–57.

    Article  CAS  PubMed  Google Scholar 

  28. Lyra ME, Andreou M, Georgantzoglou A, Kordolaimi S, Lagopati N, Ploussi A, Salvara A-L, Vamvakas I. Radionuclides used in nuclear medicine therapy – from production to dosimetry. Curr Med Imaging Rev. 2013;9(1):51–75.

    Article  CAS  Google Scholar 

  29. Strosberg J, Wolin E, Chasen B, et al. Health related quality of life in patients with progressive midgut neuroendocrine tumors treated with 177Lu-Dotatate in the phase III NETTER-1 trial. J Clin Oncol. 2018;36(25):2578–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Evans RD. Early history (1936–1946) of nuclear medicine in thyroid studies at Massachusetts General Hospital. Med Phys. 1975;2(3):105–9.

    Article  CAS  PubMed  Google Scholar 

  31. Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010;20(12):1341–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91(8):2892–9.

    Article  CAS  PubMed  Google Scholar 

  33. Haslerud T, Brauckhoff K, Reisæter L, Küfner Lein R, Heinecke A, Varhaug JE, Biermann M. F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis. Acta Radiol. 2016;57(10):1193–200.

    Article  PubMed  Google Scholar 

  34. Kim SJ, Lee TH, Kim IJ, Kim YK. Clinical implication of F-18 FDG PET/CT for differentiated thyroid cancer in patients with negative diagnostic iodine-123 scan and elevated thyroglobulin. Eur J Radiol. 2009;70(1):17–24.

    Article  PubMed  Google Scholar 

  35. Bertagna F, Bosio G, Biasiotto G, Rodella C, Puta E, Gabanelli S, Lucchini S, Merli G, Savelli G, Giubbini R, Rosenbaum J, Alavi A. F-18 FDG-PET/CT evaluation of patients with differentiated thyroid cancer with negative I-131 total body scan and high thyroglobulin level. Clin Nucl Med. 2009;34(11):756–61.

    Article  PubMed  Google Scholar 

  36. Klaus A, Fathi O, Tatjana TW, Bruno N, Oskar K. Expression of hypoxia-associated protein HIF-1α in follicular thyroid cancer is associated with distant metastasis. Pathol Oncol Res. 2018;24(2):289–96.

    Article  CAS  PubMed  Google Scholar 

  37. Ritter A, Mizrachi A, Bachar G, Vainer I, Shimon I, Hirsch D, Diker-Cohen T, Duskin-Bitan H, Robenshtok E. Detecting recurrence following lobectomy for thyroid cancer: role of thyroglobulin and thyroglobulin antibodies. J Clin Endocrinol Metab. 2020;105:1–7.

    Article  Google Scholar 

  38. Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013;368:623–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kitahara CM, et al. Association of radioactive iodine treatment with cancer mortality in patients with hyperthyroidism. JAMA Intern Med. 2019;179(8):1034–42. https://doi.org/10.1001/jamainternmed.2019.0981.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Yan KL, Li S, Tseng C-H, Kim J, Nguyen DT, Dawood NB, Livhits MJ, Yeh MW, Leung AM. Rising incidence and incidence-based mortality of thyroid cancer in California, 2000–2017. J Clin Endocrinol Metab. 2020;105(6):1–8. https://doi.org/10.1210/clinem/dgaa121.

    Article  Google Scholar 

  41. McLeod DSA, Zhang L, Durante C, Cooper DS. Contemporary debates in adult papillary thyroid cancer management. Endocr Rev. 2019;40(6):1481–99.

    Article  PubMed  Google Scholar 

  42. Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer. 1985;56(3):531–8.

    Article  CAS  PubMed  Google Scholar 

  43. Brito JP, Ito Y, Miyauchi A, Tuttle RM. A clinical framework to facilitate risk stratification when considering an active surveillance alternative to immediate biopsy and surgery in papillary microcarcinomas. Thyroid. 2016;26(1):144–9.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Durante C, Attard M, Torlontano M, Papillary Thyroid Cancer Study Group, et al. Identification and optimal postsurgical follow-up of patients with very low-risk papillary thyroid microcarcinomas. J Clin Endocrinol Metab. 2010;95(11):4882–8.

    Article  CAS  PubMed  Google Scholar 

  45. Grani G, Ramundo V, Falcone R, et al. Thyroid cancer patients with no evidence of disease: the need for repeat neck ultrasound. J Clin Endocrinol Metab. 2019;104(11):4981–9.

    Article  PubMed  Google Scholar 

  46. Klubo-Gwiezdzinska J, Van Nostrand D, Atkins F, et al. Efficacy of dosimetric versus empiric prescribed activity of 131I for therapy of differentiated thyroid cancer. J Clin Endocrinol Metabol. 2011;96(10):3217–25. https://doi.org/10.1210/JC.2011-0494.

    Article  CAS  Google Scholar 

  47. Deandreis D, Rubino C, Tala H, Leboulleux S, Terroir M, Baudin E, Larson S, Fagin JA, Schlumberger M, Tuttle RM. Comparison of empiric versus whole-body/-blood clearance dosimetry-based approach to radioactive iodine treatment in patients with metastases from differentiated thyroid cancer. J Nucl Med. 2017;58(5):717–22.

    Article  CAS  PubMed  Google Scholar 

  48. Deandreis D, Rubino C, Tala H, Leboulleux S, Terroir M, Baudin E, Larson S, Fagin JA, Schlumberger M, Tuttle RM. Comparison of empiric versus whole-body/-blood clearance dosimetry–based approach to radioactive iodine treatment in patients with metastases from differentiated thyroid cancer. J Nucl Med. 2017;58:717–22. https://doi.org/10.2967/jnumed.116.179606.

    Article  CAS  PubMed  Google Scholar 

  49. Thomas SR, Maxon HR, Kereiakes JG. In vivo quantitation of lesion radioactivity using external counting methods. Med Phys. 1976;3:253–5.

    Article  CAS  Google Scholar 

  50. Dorn R, Kopp J, Vogt H, Heidenreich P, Carroll RG, Gulec SA. Dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer: largest safe dose using a risk adapted approach. J Nucl Med. 2003;44:451–6.

    CAS  PubMed  Google Scholar 

  51. Sgouros G, Hobbs RF, Atkins FB, Van Nostrand D, Ladenson PW, Wahl RL. Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer. Eur J Nucl Med Mol Imaging. 2011;38(suppl 1):S41–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Berker Y, Goedicke A, Kemerink GJ, Aach T, Schweizer B. Activity quantification combining conjugate-view planar scintigraphies and SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy. Eur J Nucl Med Mol Imaging. 2011;38:2173–85.

    Article  CAS  PubMed  Google Scholar 

  53. Piwnica-Worms D, Holman LB. Noncardiac application of hexakis (alkylisonitrile) technetium-99m complexes. J Nucl Med. 1990;31:1166.

    CAS  PubMed  Google Scholar 

  54. Civelek AC, Durski K, Shafique I, Matsumura K, Sostre S, Wagner HN Jr, Ladenson PW. Failure of perchlorate to inhibit Tc-99m isonitrile binding by the thyroid during myocardial perfusion studies. Clin Nucl Med. 1991;16(5):358–61.

    Article  CAS  PubMed  Google Scholar 

  55. Civelek AC, Ozalp E, Donovan P, Udelsman R. Prospective evaluation of delayed technetium-99m sestamibi SPECT scintigraphy for preoperative localization of primary hyperparathyroidism. Surgery. 2002;131(2):149–57.

    Article  PubMed  Google Scholar 

  56. Bhatt G, Li XF, Civelek AC. 131I thyroid cancer therapy in chronically bedridden & dialysis patients with severe renal failure: challenges and solutions for determining the optimum therapy dose and how to minimize radiation dose to caregivers. J Nucl Med. 2014;55:1365–423.

    Google Scholar 

  57. Phegley D, Bjorklund A, Smith R, Petti M, Robichaux J, Civelek AC. Challenges and solutions for I-131 therapy in the complex inpatient with thyroid cancer: a technologist prospective. J Nucl Med. 2007;48(2):447.

    Google Scholar 

  58. Welsh JS, Yang NC, Civelek AC, Wharam MD, Williams JA. Treatment protocol for phosphorus-32 therapy for intracerebral cystic neoplasms: a preliminary report. J Brachyther Int. 1999;15(3–4):211–6.

    Google Scholar 

  59. Halperin E, Fallat M, Bond S, Crew J, Johnson R, Mills M, Bhatt G, Hughes SC, Civelek AC. Role of 32P-chromic phosphate colloids in the treatment of a skin tumors, Ewing’s sarcoma. J Nucl Med. 2012;53:1079.

    Google Scholar 

  60. Carr BI, Kondragunta V, Buch SC, Branch RA. Therapeutic equivalence in survival for hepatic arterial chemoembolization and 90Yttrium microspheres (Y90) treatments in unresectable hepatocellular carcinoma: a 2 cohort study. Cancer. 2010;116(5):1305–14.

    Article  CAS  PubMed  Google Scholar 

  61. Wang EA, Broadwell SR, Bellavia RJ, Stein JP. Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma. J Gastrointest Oncol. 2017;8(2):266–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tollefson C, Krause S, Nguyen B. Utility of SPECT/CT imaging in Y-90 microsphere therapy. J Nucl Med. 2015;56(suppl 3):2517.

    Google Scholar 

  63. Scott NP, McGowan DR. Optimising quantitative 90Y PET imaging: an investigation into the effects of scan length and Bayesian penalised likelihood reconstruction. EJNMMI Res. 2019;9:40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Salem R, et al. Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging. 2019;46:1695–704.

    Article  PubMed  Google Scholar 

  65. Nock BA, Kaloudi A, Lymperis E, et al. Theranostic perspectives in prostate cancer with the gastrin-releasing peptide receptor antagonist NeoBOMB1: preclinical and first clinical results. J Nucl Med. 2017;58(1):75–80.

    Article  CAS  PubMed  Google Scholar 

  66. Budiawan H, Salavati A, Kulkarni HR, Baum RP. Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis. J Nucl Med Mol Imaging. 2014;4(1):39–52.

    CAS  Google Scholar 

  67. Violet J, Sandhu S, Iravani A, et al. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of 177Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J Nucl Med. 2020;61:857–65.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Violet J, Sandhu S, Amir Iravani A, et al. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of 177Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J Nucl Med. 2020;61:857–65.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Allen BJ. Future prospects for targeted alpha therapy. Curr Radiopharm. 2011;4:336–42.

    Article  CAS  PubMed  Google Scholar 

  70. Morgenstern A, Bruchertseifer F, Apostolidis C. Bismuth-213 and Actinium-225 – generator performance and evolving therapeutic applications of two generator-derived alpha-emitting radioisotopes. Curr Radiopharm. 2012;5(3):221–7.

    Article  CAS  PubMed  Google Scholar 

  71. Wong F, Naff K, Liu C, Ferguson A, Hwu P. Intratumoral positron emission cancer therapy (IPECT) using F-18 FDG, Cu-64 Cl and Ga-68 Cl. J Nucl Med. 2013;54(supplement 2):1400.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Cahid Civelek .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Civelek, A.C., Wong, F.C.L. (2021). Radionuclide Cancer Therapy: Unsealed Alpha- and Beta-Emitters. In: Wong, F.C. (eds) Locoregional Radionuclide Cancer Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-56267-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-56267-0_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-56266-3

  • Online ISBN: 978-3-030-56267-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics