Skip to main content
SpringerLink
Log in

The Radiobiology of Radiopharmaceutical Therapy: The Input of Imaging and Radiomics

  • Chapter
  • First Online:
Radiopharmaceutical Therapy

  • 728 Accesses

Abstract

Radiopharmaceutical therapy (RPT) is a radiotherapeutic modality that is predicated on the specific irradiation of tumours by radiolabelled biomolecules directed against tumour cells or their microenvironment. In contrast to conventional external beam radiotherapy, RPT is characterized by heterogeneous and continuous low dose rate irradiation and can use both high- to low-linear energy transfer depending on the radionuclide chosen. In light of these properties, the radiobiology of RPT must be specifically addressed. Furthermore, given the increasing number of patients treated by RPT, the study of radiobiology should no longer be restricted to preclinical experiments and should be extended to clinical research. The implementation of clinical radiobiology requires the analysis of patient samples and the use of non-invasive imaging approaches to extract tumour features that are indicative of response to RPT.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
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

References

  1. Herrmann K, Schwaiger M, Lewis JS, Solomon SB, McNeil BJ, Baumann M, et al. Radiotheranostics: a roadmap for future development. Lancet Oncol. 2020;21(3):e146–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pouget JP, Lozza C, Deshayes E, Boudousq V, Navarro-Teulon I. Introduction to radiobiology of targeted radionuclide therapy. Front Med (Lausanne). 2015;2:12.

    PubMed  Google Scholar 

  3. Pouget JP, Constanzo J. Revisiting the radiobiology of targeted alpha therapy. Front Med (Lausanne). 2021;8:692436.

    Article  PubMed  PubMed Central  Google Scholar 

  4. EANM Radiobiology Working Group, Pouget JP, Konijnenberg M, Eberlein U, Glatting G, Gabina PM, et al. An EANM position paper on advancing radiobiology for shaping the future of nuclear medicine. Eur J Nucl Med Mol Imaging. 2022; https://doi.org/10.1007/s00259-022-05934-2.

  5. Holsti LR. Development of clinical radiotherapy since 1896. Acta Oncol. 1995;34(8):995–1003.

    Article  CAS  PubMed  Google Scholar 

  6. Puck TT, Marcus PI. Action of X-Rays on mammalian cells. J Exp Med. 1956;103(5):653–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Turesson I. Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation. Radiother Oncol. 1990;19(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  8. Van Der Kogel AJ. The dose-rate effect. In: Joiner M, van der Kogel A, editors. Basic clinical radiobiology. London: Hodder Arnold; 2009.

    Chapter  Google Scholar 

  9. Thames HD. Repair kinetics in tissues: alternative models. Radiother Oncol. 1989;14(4):321–7.

    Article  CAS  PubMed  Google Scholar 

  10. Ku A, Facca VJ, Cai Z, Reilly RM. Auger electrons for cancer therapy – a review. EJNMMI Radiopharm Chem [Internet]. 2019 [cited 2021 Jun 8];4(1):27. Available from: https://ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-019-0075-2.

  11. Goodhead DT. Spatial and temporal distribution of energy. Health Phys [Internet]. 1988 [cited 2021 Jul 6];55(2):231–40. Available from: http://journals.lww.com/00004032-198808000-00015.

  12. Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J [Internet]. 1984 [cited 2022 Dec 10];219(1):1–14. Available from: https://portlandpress.com/biochemj/article/219/1/1/15857/Oxygen-toxicity-oxygen-radicals-transition-metals.

  13. Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL, et al. Hydroxyl radicals and DNA base damage. Mutat Res. 1999;424(1–2):9–21.

    Article  CAS  PubMed  Google Scholar 

  14. Laurent C, Voisin P, Pouget JP. DNA damage in cultured skin microvascular endothelial cells exposed to gamma rays and treated by the combination pentoxifylline and α-tocopherol. Int J Radiat Biol [Internet]. 2006 [cited 2022 Dec 9];82(5):309–21. Available from: http://www.tandfonline.com/doi/full/10.1080/09553000600733150.

  15. Cadet J, Douki T, Ravanat JL. One-electron oxidation of DNA and inflammation processes. Nat Chem Biol [Internet]. 2006 [cited 2022 Dec 10];2(7):348–9. Available from: http://www.nature.com/articles/nchembio0706-348.

  16. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OCA. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. BJR [Internet]. 1953 [cited 2021 Jun 1];26(312):638–48. Available from: http://www.birpublications.org/doi/10.1259/0007-1285-26-312-638.

  17. Wright EA, Howard-Flanders P. The influence of oxygen on the radiosensitivity of mammalian tissues. Acta Radiol. 1957;48(1):26–32.

    Article  CAS  PubMed  Google Scholar 

  18. Carles M, Fechter T, Grosu AL, Sörensen A, Thomann B, Stoian RG, et al. 18F-FMISO-PET hypoxia monitoring for head-and-neck cancer patients: radiomics analyses predict the outcome of chemo-radiotherapy. Cancers (Basel). 2021;13(14):3449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dietz DW, Dehdashti F, Grigsby PW, Malyapa RS, Myerson RJ, Picus J, et al. Tumor hypoxia detected by positron emission tomography with 60Cu-ATSM as a predictor of response and survival in patients undergoing Neoadjuvant chemoradiotherapy for rectal carcinoma: a pilot study. Dis Colon Rectum. 2008;51(11):1641–8.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dehdashti F, Grigsby PW, Lewis JS, Laforest R, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by PET with 60Cu-Labeled Diacetyl-Bis(N4-Methylthiosemicarbazone). J Nucl Med. 2008;49(2):201–5.

    Article  CAS  PubMed  Google Scholar 

  21. Nachankar A, Oike T, Hanaoka H, Kanai A, Sato H, Yoshida Y, et al. 64Cu-ATSM predicts efficacy of carbon ion radiotherapy associated with cellular antioxidant capacity. Cancers. 2021;13(24):6159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huizing FJ, Garousi J, Lok J, Franssen G, Hoeben BAW, Frejd FY, et al. CAIX-targeting radiotracers for hypoxia imaging in head and neck cancer models. Sci Rep. 2019;9(1):18898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ueda M, Kudo T, Mutou Y, Umeda IO, Miyano A, Ogawa K, et al. Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor: comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry. Cancer Sci. 2011;102(11):2090–6.

    Article  CAS  PubMed  Google Scholar 

  24. Huang Y, Fan J, Li Y, Fu S, Chen Y, Wu J. Imaging of tumor hypoxia with radionuclide-labeled tracers for PET. Front Oncol [Internet]. 2021 [cited 2022 May 13];11. Available from: https://www.frontiersin.org/article/10.3389/fonc.2021.731503.

  25. Auerswald S, Schreml S, Meier R, Blancke Soares A, Niyazi M, Marschner S, et al. Wound monitoring of pH and oxygen in patients after radiation therapy. Radiat Oncol. 2019;14:199.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Choi EK, Roberts KP, Griffin RJ, Han T, Park HJ, Song CW, et al. Effect of pH on radiation-induced p53 expression. Int J Radiat Oncol Biol Phys. 2004;60(4):1264–71.

    Article  CAS  PubMed  Google Scholar 

  27. Pereira PMR, Edwards KJ, Mandleywala K, Carter LM, Escorcia FE, Campesato LF, et al. iNOS regulates the therapeutic response of pancreatic cancer cells to radiotherapy. Cancer Res. 2020;80(8):1681–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Frankenberg-Schwager M. Review of repair kinetics for DNA damage induced in eukaryotic cells in vitro by ionizing radiation. Radiother Oncol [Internet]. 1989 [cited 2021 Jul 6];14(4):307–20. Available from: https://linkinghub.elsevier.com/retrieve/pii/0167814089901436.

  29. Goodhead DT. Initial events in the cellular effects of ionizing radiations: clustered damage in DNA. Int J Radiat Biol [Internet]. 1994 [cited 2021 May 31];65(1):7–17. Available from: http://www.tandfonline.com/doi/full/10.1080/09553009414550021.

  30. Signore A, Campagna G, Marinaccio J, de Vitis M, Lauri C, Berardinelli F, et al. Analysis of short term and stable DNA damage in patients with differentiated thyroid cancer treated with 131 I in hypothyroidism or with rhTSH for remnant ablation. J Nucl Med [Internet]. 2022 [cited 2022 Aug 31]. Available from: http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.121.263442.

  31. Lassmann M, Hänscheid H, Gassen D, Biko J, Meineke V, Reiners C, et al. In vivo formation of γ-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer. J Nucl Med [Internet]. 2010 [cited 2022 Aug 31];51(8):1318–25. Available from: http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.109.071357.

  32. Schumann S, Scherthan H, Pfestroff K, Schoof S, Pfestroff A, Hartrampf P, et al. DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with 131I. Eur J Nucl Med Mol Imaging. 2022;49(5):1447–55.

    Article  CAS  PubMed  Google Scholar 

  33. Schumann S, Eberlein U, Lapa C, Müller J, Serfling S, Lassmann M, et al. α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients. Eur J Nucl Med Mol Imaging [Internet]. 2021 [cited 2022 Aug 31];48(9):2761–70. Available from: https://link.springer.com/10.1007/s00259-020-05170-6.

  34. Eberlein U, Scherthan H, Bluemel C, Peper M, Lapa C, Buck AK, et al. DNA damage in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy. J Nucl Med [Internet]. 2016 [cited 2022 Aug 31];57(2):173–9. Available from: http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.115.164814.

  35. Lomax EM, Gulston KM, O’Neill P. Chemical aspects of clustered DNA damage induction by ionising radiation. Radiat Protect Dosim [Internet]. 2002 [cited 2021 Mar 3];99(1):63–8. Available from: https://academic.oup.com/rpd/article-lookup/doi/10.1093/oxfordjournals.rpd.a006840.

  36. Eccles LJ, O’Neill P, Lomax ME. Delayed repair of radiation induced clustered DNA damage: friend or foe? Mutat Res. 2011;711(1–2):134–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pouget JP, Frelon S, Ravanat JL, Testard I, Odin F, Cadet J. Formation of modified DNA bases in cells exposed either to gamma radiation or to high-LET particles. Radiat Res [Internet]. 2002 [cited 2021 May 31];157(5):589–95. Available from: http://www.bioone.org/doi/abs/10.1667/0033-7587%282002%29157%5B0589%3AFOMDBI%5D2.0.CO%3B2.

  38. Sasaki MS. Advances in the biophysical and molecular bases of radiation cytogenetics. Int J Radiat Biol [Internet]. 2009 [cited 2022 Dec 9];85(1):26–47. Available from: http://www.tandfonline.com/doi/full/10.1080/09553000802641185.

  39. Georgakilas A. Detection of clustered DNA lesions: biological and clinical applications. World J Biol Chem. 2011;2(7):173–6.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sage E, Shikazono N. Radiation-induced clustered DNA lesions: repair and mutagenesis. Free Radic Biol Med. 2017;107:125–35.

    Article  CAS  PubMed  Google Scholar 

  41. Amoretti M, Amsler C, Bonomi G, Bouchta A, Bowe P, Carraro C, et al. Production and detection of cold antihydrogen atoms. Nature. 2002;419(6906):456–9.

    Article  CAS  PubMed  Google Scholar 

  42. Rothkamm K, Krüger I, Thompson LH, Löbrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol [Internet]. 2003 [cited 2022 Dec 10];23(16):5706–15. Available from: https://journals.asm.org/doi/10.1128/MCB.23.16.5706-5715.2003.

  43. Rothkamm K, Krüger I, Thompson LH, Löbrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 2003;23(16):5706–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shibata A, Jeggo P, Löbrich M. The pendulum of the Ku-Ku clock. DNA Repair (Amst). 2018;71:164–71.

    Article  CAS  PubMed  Google Scholar 

  45. Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol. 2013;14(4):197–210.

    Article  CAS  PubMed  Google Scholar 

  46. Marechal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol [Internet]. 2013 [cited 2022 Oct 10];5(9):a012716. Available from: http://cshperspectives.cshlp.org/lookup/doi/10.1101/cshperspect.a012716.

  47. Panier S, Boulton SJ. Double-strand break repair: 53BP1 comes into focus. Nat Rev Mol Cell Biol [Internet]. 2014 [cited 2021 May 29];15(1):7–18. Available from: http://www.nature.com/articles/nrm3719.

  48. Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355(6330):1152–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Paillas S, Boudousq V, Piron B, Kersual N, Bardiès M, Chouin N, et al. Apoptosis and p53 are not involved in the anti-tumor efficacy of 125I-labeled monoclonal antibodies targeting the cell membrane. Nucl Med Biol. 2013;40(4):471–80.

    Article  CAS  PubMed  Google Scholar 

  50. Lundsten S, Berglund H, Jha P, Krona C, Hariri M, Nelander S, et al. p53-Mediated radiosensitization of 177Lu-DOTATATE in neuroblastoma tumor spheroids. Biomol Ther. 2021;11(11):1695.

    CAS  Google Scholar 

  51. Privé BM, Slootbeek PHJ, Laarhuis BI, Naga SP, van der Doelen MJ, van Kalmthout LWM, et al. Impact of DNA damage repair defects on response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis [Internet]. 2022 [cited 2022 Aug 31];25(1):71–8. Available from: https://www.nature.com/articles/s41391-021-00424-2.

  52. van der Doelen MJ, Mehra N, van Oort IM, Looijen-Salamon MG, Janssen MJR, Custers JAE, et al. Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy. Urol Oncol: Semin Orig Investig [Internet]. 2021 [cited 2022 Dec 9];39(10):729.e7–16. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1078143920306311.

  53. Zhu M, Sonbol MB, Halfdanarson T, Hobday T, Ahn D, Ma WW, et al. Homologous recombination repair defect may predict treatment response to peptide receptor radionuclide therapy for neuroendocrine tumors. Oncologist [Internet]. 2020 [cited 2022 Dec 9];25(8):e1246–8. Available from: https://academic.oup.com/oncolo/article/25/8/e1246/6443870.

  54. Wickstroem K, Hagemann UB, Cruciani V, Wengner AM, Kristian A, Ellingsen C, et al. Synergistic effect of a mesothelin-targeted 227 Th conjugate in combination with DNA damage response inhibitors in ovarian cancer xenograft models. J Nucl Med [Internet]. 2019 [cited 2022 Dec 9];60(9):1293–300. Available from: http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.118.223701.

  55. Makvandi M, Lee H, Puentes LN, Reilly SW, Rathi KS, Weng CC, et al. Targeting PARP-1 with alpha-particles is potently cytotoxic to human neuroblastoma in preclinical models. Mol Cancer Ther. 2019;18(7):1195–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Jannetti SA, Carlucci G, Carney B, Kossatz S, Shenker L, Carter LM, et al. PARP-1–targeted radiotherapy in mouse models of glioblastoma. J Nucl Med. 2018;59(8):1225–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Fu J, Qiu F, Stolniceanu CR, Yu F, Zang S, Xiang Y, et al. Combined use of 177 Lu-DOTATATE peptide receptor radionuclide therapy and fluzoparib for treatment of well-differentiated neuroendocrine tumors: a preclinical study. J Neuroendocrinol [Internet]. 2022 [cited 2022 Dec 9];34(4). Available from: https://onlinelibrary.wiley.com/doi/10.1111/jne.13109.

  58. Purohit NK, Shah RG, Adant S, Hoepfner M, Shah GM, Beauregard JM. Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor. Oncotarget. 2018;9(37):24693–706.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Pirovano G, Jannetti SA, Carter LM, Sadique A, Kossatz S, Guru N, et al. Targeted brain tumor radiotherapy using an auger emitter. Clin Cancer Res. 2020;26(12):2871–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Atkinson J, Bezak E, Kempson I. Imaging DNA double-strand breaks — are we there yet? Nat Rev Mol Cell Biol [Internet]. 2022 [cited 2022 Aug 31]. Available from: https://www.nature.com/articles/s41580-022-00513-7.

  61. Piron B, Paillas S, Boudousq V, Pèlegrin A, Bascoul-Mollevi C, Chouin N, et al. DNA damage-centered signaling pathways are effectively activated during low dose-rate Auger radioimmunotherapy. Nucl Med Biol. 2014;41:e75–83.

    Article  CAS  PubMed  Google Scholar 

  62. Knight JC, Koustoulidou S, Cornelissen B. Imaging the DNA damage response with PET and SPECT. Eur J Nucl Med Mol Imaging. 2017;44(6):1065–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cornelissen B, Kersemans V, Darbar S, Thompson J, Shah K, Sleeth K, et al. Imaging DNA damage in vivo using gammaH2AX-targeted immunoconjugates. Cancer Res. 2011;71(13):4539–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Knight JC, Topping C, Mosley M, Kersemans V, Falzone N, Fernández-Varea JM, et al. PET imaging of DNA damage using (89)Zr-labelled anti-γH2AX-TAT immunoconjugates. Eur J Nucl Med Mol Imaging. 2015;42(11):1707–17.

    Article  CAS  PubMed  Google Scholar 

  65. Cornelissen B, Darbar S, Kersemans V, Allen D, Falzone N, Barbeau J, et al. Amplification of DNA damage by a γH2AX-targeted radiopharmaceutical. Nucl Med Biol. 2012;39(8):1142–51.

    Article  CAS  PubMed  Google Scholar 

  66. O’Neill E, Kersemans V, Allen PD, Terry SYA, Torres JB, Mosley M, et al. Imaging DNA damage repair in vivo following 177Lu-DOTATATE therapy. J Nucl Med [Internet]. 2019 [cited 2022 May 16]. Available from: https://jnm.snmjournals.org/content/early/2019/11/21/jnumed.119.232934.

  67. Poty S, Mandleywala K, O’Neill E, Knight JC, Cornelissen B, Lewis JS. 89Zr-PET imaging of DNA double-strand breaks for the early monitoring of response following α- and β-particle radioimmunotherapy in a mouse model of pancreatic ductal adenocarcinoma. Theranostics. 2020;10(13):5802–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Carney B, Kossatz S, Reiner T. Molecular imaging of PARP. J Nucl Med. 2017;58(7):1025–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. de Souza D, França P, Kossatz S, Brand C, Karassawa Zanoni D, Roberts S, Guru N, et al. A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer. Eur J Nucl Med Mol Imaging. 2021;48(11):3618–30.

    Article  Google Scholar 

  70. Schöder H, França PDDS, Nakajima R, Burnazi E, Roberts S, Brand C, et al. Safety and feasibility of PARP1/2 imaging with 18F-PARPi in patients with head and neck cancer. Clin Cancer Res. 2020;26(13):3110–6.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Kossatz S, Weber WA, Reiner T. Optical imaging of PARP1 in response to radiation in oral squamous cell carcinoma. PLoS One. 2016;11(1):e0147752.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ladjohounlou R, Lozza C, Pichard A, Constanzo J, Karam J, Le Fur P, et al. Drugs that modify cholesterol metabolism alter the p38/JNK-mediated targeted and nontargeted response to alpha and auger radioimmunotherapy. Clin Cancer Res [Internet]. 2019 [cited 2021 Feb 9];25(15):4775–90. Available from: http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-18-3295.

  73. Haimovitz-Friedman A, Kan CC, Ehleiter D, Persaud RS, McLoughlin M, Fuks Z, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med [Internet]. 1994 [cited 2021 Mar 26];180(2):525–35. Available from: https://rupress.org/jem/article/180/2/525/50763/Ionizing-radiation-acts-on-cellular-membranes-to.

  74. Zirkle RE. Radiation biology. In: Hollaender A, editor. The radiobiological importance of linear energy transfer. New York: McGraw-Hill Book Company; 1954. p. 315–50.

    Google Scholar 

  75. Munro TR. The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat Res [Internet]. 1970 [cited 2021 Mar 22];42(3):451. Available from: https://www.jstor.org/stable/3572962?origin=crossref.

  76. Nagasawa H, Cremesti A, Kolesnick R, Fuks Z, Little JB. Involvement of membrane signaling in the bystander effect in irradiated cells. Cancer Res. 2002;62(9):2531–4.

    CAS  PubMed  Google Scholar 

  77. Shao C, Folkard M, Michael BD, Prise KM. Targeted cytoplasmic irradiation induces bystander responses. Proc Natl Acad Sci [Internet]. 2004 [cited 2021 Mar 26];101(37):13495–500. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0404930101.

  78. Hong M, Xu A, Zhou H, Wu L, Randers-Pehrson G, Santella RM, et al. Mechanism of genotoxicity induced by targeted cytoplasmic irradiation. Br J Cancer [Internet]. 2010 [cited 2021 Mar 31];103(8):1263–8. Available from: http://www.nature.com/articles/6605888.

  79. Zhang B, Davidson MM, Zhou H, Wang C, Walker WF, Hei TK. Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent mitochondrial fission. Cancer Res [Internet]. 2013 [cited 2021 Mar 31];73(22):6700–10. Available from: http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-13-1411.

  80. Leach JK, Van Tuyle G, Lin PS, Schmidt-Ullrich R, Mikkelsen RB. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res. 2001;61(10):3894–901.

    CAS  PubMed  Google Scholar 

  81. Kim JG, Chandrasekaran K, Morgan FW. Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review. Mutagenesis [Internet]. 2006 [cited 2021 Mar 23];21(6):361–7. Available from: https://academic.oup.com/mutage/article-lookup/doi/10.1093/mutage/gel048.

  82. Kam WWY, Banati RB. Effects of ionizing radiation on mitochondria. Free Radic Biol Med [Internet]. 2013 [cited 2020 Sep 14];65:607–19. Available from: http://www.sciencedirect.com/science/article/pii/S0891584913003687.

  83. Walsh DWM, Siebenwirth C, Greubel C, Ilicic K, Reindl J, Girst S, et al. Live cell imaging of mitochondria following targeted irradiation in situ reveals rapid and highly localized loss of membrane potential. Sci Rep [Internet]. 2017 [cited 2021 Mar 23];7(1):46684. Available from: http://www.nature.com/articles/srep46684.

  84. Wu J, Zhang B, Wuu YR, Davidson MM, Hei TK. Targeted cytoplasmic irradiation and autophagy. Mutat Res/Fundam Mol Mech Mutagen [Internet]. 2017 [cited 2021 Mar 23];806:88–97. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0027510716301476.

  85. Pouget JP, Georgakilas AG, Ravanat JL. Targeted and off-target (bystander and abscopal) effects of radiation therapy: redox mechanisms and risk/benefit analysis. Antioxid Redox Signal [Internet]. 2018 [cited 2021 Mar 23];29(15):1447–87. Available from: https://www.liebertpub.com/doi/10.1089/ars.2017.7267.

  86. Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature [Internet]. 2004 [cited 2021 Jun 1];432(7015):316–23. Available from: http://www.nature.com/articles/nature03097.

  87. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17(2):93–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Suman S, Priya R, Kameswaran M. Induction of different cellular arrest and molecular responses in low EGFR expressing A549 and high EGFR expressing A431 tumor cells treated with various doses of 177 Lu-Nimotuzumab. Int J Radiat Biol [Internet]. 2020 [cited 2022 Aug 31];96(9):1144–56. Available from: https://www.tandfonline.com/doi/full/10.1080/09553002.2020.1793012.

  89. Pichard A, Marcatili S, Karam J, Constanzo J, Ladjohounlou R, Courteau A, et al. The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest. Leukemia [Internet]. 2020 [cited 2021 Jun 2];34(5):1315–28. Available from: http://www.nature.com/articles/s41375-019-0677-4.

  90. Supiot S, Gouard S, Charrier J, Apostolidis C, Chatal JF, Barbet J, et al. Mechanisms of cell sensitization to α radioimmunotherapy by doxorubicin or paclitaxel in multiple myeloma cell lines. Clin Cancer Res [Internet]. 2005 [cited 2022 Oct 10];11(19):7047s–52s. Available from: https://aacrjournals.org/clincancerres/article/11/19/7047s/190792/Mechanisms-of-Cell-Sensitization-to.

  91. Lindenblatt D, Terraneo N, Pellegrini G, Cohrs S, Spycher PR, Vukovic D, et al. Combination of lutetium-177 labelled anti-L1CAM antibody chCE7 with the clinically relevant protein kinase inhibitor MK1775: a novel combination against human ovarian carcinoma. BMC Cancer [Internet]. 2018 [cited 2022 Dec 9];18(1):922. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4836-1.

  92. Pan MH, Huang SC, Liao YP, Schaue D, Wang CC, Stout DB, et al. FLT-PET imaging of radiation responses in murine tumors. Mol Imaging Biol. 2008;10(6):325–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. In vivo validation of 3’deoxy-3’-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res. 2002;8(11):3315–23.

    CAS  PubMed  Google Scholar 

  94. Vera P, Bohn P, Edet-Sanson A, Salles A, Hapdey S, Gardin I, et al. Simultaneous positron emission tomography (PET) assessment of metabolism with 18F-fluoro-2-deoxy-d-glucose (FDG), proliferation with 18F-fluoro-thymidine (FLT), and hypoxia with 18fluoro-misonidazole (F-miso) before and during radiotherapy in patients with non-small-cell lung cancer (NSCLC): a pilot study. Radiother Oncol. 2011;98(1):109–16.

    Article  CAS  PubMed  Google Scholar 

  95. Ahlstedt J, Johansson E, Sydoff M, Karlsson H, Thordarson E, Gram M, et al. Non-Invasive imaging methodologies for assessment of radiation damage to bone marrow and kidneys from peptide receptor radionuclide therapy. Neuroendocrinology. 2020;110(1–2):130–8.

    Article  CAS  PubMed  Google Scholar 

  96. Constanzo J, Garcia-Prada CD, Pouget JP. Clonogenic assay to measure bystander cytotoxicity of targeted alpha-particle therapy. In: Methods in cell biology [Internet]. Elsevier; 2022 [cited 2022 Dec 10]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0091679X22001303.

  97. Guo MF, Zhao Y, Tian R, Li L, Guo L, Xu F, et al. In vivo99mTc-HYNIC-annexin V imaging of early tumor apoptosis in mice after single dose irradiation. J Exp Clin Cancer Res. 2009;28(1):136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kartachova M, Haas RLM, Valdés Olmos RA, Hoebers FJP, van Zandwijk N, Verheij M. In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in relation to treatment response. Radiother Oncol. 2004;72(3):333–9.

    Article  CAS  PubMed  Google Scholar 

  99. Allen AM, Ben-Ami M, Reshef A, Steinmetz A, Kundel Y, Inbar E, et al. Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with 18F-ML-10. Eur J Nucl Med Mol Imaging. 2012;39(9):1400–8.

    Article  PubMed  Google Scholar 

  100. García-Argüello SF, Lopez-Lorenzo B, Cornelissen B, Smith G. Development of [18F]ICMT-11 for imaging caspase-3/7 activity during therapy-induced apoptosis. Cancers (Basel). 2020;12(8):E2191.

    Article  Google Scholar 

  101. Challapalli A, Kenny LM, Hallett WA, Kozlowski K, Tomasi G, Gudi M, et al. 18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry. J Nucl Med. 2013;54(9):1551–6.

    Article  CAS  PubMed  Google Scholar 

  102. Dubash SR, Merchant S, Heinzmann K, Mauri F, Lavdas I, Inglese M, et al. Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer. Eur J Nucl Med Mol Imaging. 2018;45(13):2285–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kolb H, Walsh J, Mocharla V, Liang Q, Zhao T, Gomez F, et al. 18F-CP18: A novel DEVD containing peptide substrate for imaging apoptosis via Caspase-3 activity. J Nucl Med. 2011;52(supplement 1):350.

    Google Scholar 

  104. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31–46.

    Article  CAS  PubMed  Google Scholar 

  105. Tung CH, Zeng Q, Shah K, Kim DE, Schellingerhout D, Weissleder R. In Vivo imaging of β-Galactosidase activity using far red fluorescent switch. Cancer Res. 2004;64(5):1579–83.

    Article  CAS  PubMed  Google Scholar 

  106. Krueger MA, Cotton JM, Zhou B, Wolter K, Schwenck J, Kuehn A, et al. Abstract 1146: [18F]FPyGal: a novel ß-galactosidase specific PET tracer for in vivo imaging of tumor senescence. Cancer Res. 2019;79(13_Supplement):1146.

    Article  Google Scholar 

  107. Barberet P, Seznec H. Advances in microbeam technologies and applications to radiation biology: Table 1. Radiat Prot Dosimetry [Internet]. 2015 [cited 2021 Mar 23];166(1–4):182–7. Available from: https://academic.oup.com/rpd/article-lookup/doi/10.1093/rpd/ncv192.

  108. Paillas S, Ladjohounlou R, Lozza C, Pichard A, Boudousq V, Jarlier M, et al. Localized irradiation of cell membrane by auger electrons is cytotoxic through oxidative stress-mediated nontargeted effects. Antioxid Redox Signal [Internet]. 2016 [cited 2021 Feb 9];25(8):467–84. Available from: http://www.liebertpub.com/doi/10.1089/ars.2015.6309.

  109. Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol 2009 [cited 2022 Dec 10];10(7):718–26. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1470204509700828.

  110. Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004 [cited 2019 Nov 2];58(3):862–70. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0360301603019382.

  111. Demaria S, Formenti SC. Role of T lymphocytes in tumor response to radiotherapy. Front Oncol [Internet]. 2012 [cited 2021 Nov 1];2. Available from: http://journal.frontiersin.org/article/10.3389/fonc.2012.00095/abstract.

  112. Lejeune P, Cruciani V, Berg-Larsen A, Schlicker A, Mobergslien A, Bartnitzky L, et al. Immunostimulatory effects of targeted thorium-227 conjugates as single agent and in combination with anti-PD-L1 therapy. J Immunother Cancer. 2021;9(10):e002387.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Patel RB, Hernandez R, Carlson P, Grudzinski J, Bates AM, Jagodinsky JC, et al. Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade. Sci Transl Med [Internet]. 2021 [cited 2021 Oct 23];13(602):eabb3631. Available from: https://www.science.org/doi/10.1126/scitranslmed.abb3631.

  114. Constanzo J, Galluzzi L, Pouget JP. Immunostimulatory effects of radioimmunotherapy. J Immunother Cancer [Internet]. 2022 [cited 2022 May 30];10(2):e004403. Available from: https://jitc.bmj.com/lookup/doi/10.1136/jitc-2021-004403.

  115. Rodriguez-Ruiz ME, Vitale I, Harrington KJ, Melero I, Galluzzi L. Immunological impact of cell death signaling driven by radiation on the tumor microenvironment. Nat Immunol [Internet]. 2020 [cited 2020 Oct 5];21(2):120–34. Available from: https://www.nature.com/articles/s41590-019-0561-4.

  116. Vanpouille-Box C, Demaria S, Formenti SC, Galluzzi L. Cytosolic DNA sensing in organismal tumor control. Cancer Cell [Internet]. 2018 [cited 2021 Jul 5];34(3):361–78. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1535610818302277.

  117. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Röhl I, et al. cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING. Nature [Internet]. 2013 [cited 2021 Jul 5];498(7454):380–4. Available from: http://www.nature.com/articles/nature12306.

  118. Kristensen LK, Christensen C, Alfsen MZ, Cold S, Nielsen CH, Kjaer A. Monitoring CD8a+ T cell responses to radiotherapy and CTLA-4 blockade using [64Cu]NOTA-CD8a PET imaging. Mol Imaging Biol. 2020;22(4):1021–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Luo X, Hu D, Gao D, Wang Y, Chen X, Liu X, et al. Metabolizable near-infrared-II nanoprobes for dynamic imaging of deep-seated tumor-associated macrophages in pancreatic cancer. ACS Nano. 2021;15(6):10010–24.

    Article  CAS  PubMed  Google Scholar 

  120. Ehlerding EB, Lee HJ, Barnhart TE, Jiang D, Kang L, McNeel DG, et al. Noninvasive imaging and quantification of radiotherapy-induced PD-L1 upregulation with 89Zr–Df–Atezolizumab. Bioconjug Chem. 2019;30(5):1434–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Heskamp S, Wierstra PJ, Molkenboer-Kuenen JDM, Sandker GW, Thordardottir S, Cany J, et al. PD-L1 microSPECT/CT imaging for longitudinal monitoring of PD-L1 expression in syngeneic and humanized mouse models for cancer. Cancer Immunol Res. 2019;7(1):150–61.

    Article  CAS  PubMed  Google Scholar 

  122. Hartimath S, Draghiciu O, Daemen T, Nijman HW, van Waarde A, Dierckx RAJO, et al. Therapy-induced changes in CXCR4 expression in tumor xenografts can be monitored noninvasively with N-[11C]Methyl-AMD3465 PET. Mol Imaging Biol. 2020;22(4):883–90.

    Article  CAS  PubMed  Google Scholar 

  123. Zips D. Tumour growth and response to radiation. In: Joiner M, van der Kogel A, editors. Basic clinical radiobiology. London: Hodder Arnold; 2009.

    Google Scholar 

  124. Cremonesi M, Ferrari ME, Bodei L, Chiesa C, Sarnelli A, Garibaldi C, et al. Correlation of dose with toxicity and tumour response to 90Y- and 177Lu-PRRT provides the basis for optimization through individualized treatment planning. Eur J Nucl Med Mol Imaging [Internet]. 2018 [cited 2021 Feb 9];45(13):2426–41. Available from: http://link.springer.com/10.1007/s00259-018-4044-x.

  125. Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging [Internet]. 2015 [cited 2019 Nov 2];42(1):5–19. Available from: http://link.springer.com/10.1007/s00259-014-2893-5.

  126. Bodei L, Kidd M, Baum RP, Modlin IM. PRRT: defining the paradigm shift to achieve standardization and individualization. J Nucl Med [Internet]. 2014 [cited 2022 Dec 11];55(11):1753–6. Available from: http://jnm.snmjournals.org/lookup/doi/10.2967/jnumed.114.143974.

  127. Williams JA, Edwards JA, Dillehay LE. Quantitative comparison of radiolabeled antibody therapy and external beam radiotherapy in the treatment of human glioma xenografts. Int J Radiat Oncol Biol Phys [Internet]. 1992 [cited 2022 Dec 10];24(1):111–7. Available from: https://linkinghub.elsevier.com/retrieve/pii/036030169291029M.

  128. Herrera FG, Ronet C, Ochoa de Olza M, Barras D, Crespo I, Andreatta M, et al. Low dose radiotherapy reverses tumor immune desertification and resistance to immunotherapy. Cancer Discov [Internet]. 2021[cited 2021 Oct 29];candisc.0003.2021. Available from: http://cancerdiscovery.aacrjournals.org/lookup/doi/10.1158/2159-8290.CD-21-0003.

  129. Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 2006;6(9):702–13.

    Article  CAS  PubMed  Google Scholar 

  130. Prise KM, O’Sullivan JM. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer [Internet]. 2009 [cited 2021 Apr 8];9(5):351–60. Available from: http://www.nature.com/articles/nrc2603.

  131. Jeraj R, Bradshaw T, Simončič U. Molecular imaging to plan radiotherapy and evaluate its efficacy. J Nucl Med. 2015;56(11):1752–65.

    Article  CAS  PubMed  Google Scholar 

  132. Terry SYA, Nonnekens J, Aerts A, Baatout S, de Jong M, Cornelissen B, et al. Call to arms: need for radiobiology in molecular radionuclide therapy. Eur J Nucl Med Mol Imaging. 2019;46(8):1588–90.

    Article  PubMed  Google Scholar 

  133. Kumar V, Gu Y, Basu S, Berglund A, Eschrich SA, Schabath MB, et al. Radiomics: the process and the challenges. Magn Reson Imaging. 2012;30(9):1234–48.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Gillies RJ, Kinahan PE, Hricak H. Radiomics: images are more than pictures, they are data. Radiology. 2016;278(2):563–77.

    Article  PubMed  Google Scholar 

  135. Hatt M, Vallieres M, Visvikis D, Zwanenburg A. IBSI: an international community radiomics standardization initiative. J Nucl Med. 2018;59(supplement 1):287.

    Google Scholar 

  136. Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RGPM, Granton P, et al. Radiomics: Extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012;48(4):441–6.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Haralick RM, Shanmugam K, Dinstein I. Textural features for image classification. IEEE Trans Syst Man Cybern. 1973;3(6):610–21.

    Article  Google Scholar 

  138. Avanzo M, Wei L, Stancanello J, Vallières M, Rao A, Morin O, et al. Machine and deep learning methods for radiomics. Med Phys. 2020;47(5):e185–202.

    Article  PubMed  Google Scholar 

  139. Avanzo M, Stancanello J, El Naqa I. Beyond imaging: the promise of radiomics. Phys Med. 2017;38:122–39.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553, INCa-Cancéropôle GSO, AVIESAN PCSI (#ASC20025FSA), LABEX MabImprove, Région Occitanie and Fondation ARC pour la Recherche sur le Cancer.

Author information

Authors and Affiliations

  1. Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France

    Jean-Pierre Pouget, Marion Tardieu & Sophie Poty

Authors
  1. Jean-Pierre Pouget
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marion Tardieu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie Poty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jean-Pierre Pouget or Sophie Poty .

Editor information

Editors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lisa Bodei

  2. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jason S. Lewis

  3. Hunter College - CUNY, New York, NY, USA

    Brian M. Zeglis

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pouget, JP., Tardieu, M., Poty, S. (2023). The Radiobiology of Radiopharmaceutical Therapy: The Input of Imaging and Radiomics. In: Bodei, L., Lewis, J.S., Zeglis, B.M. (eds) Radiopharmaceutical Therapy. Springer, Cham. https://doi.org/10.1007/978-3-031-39005-0_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-39005-0_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-39004-3

  • Online ISBN: 978-3-031-39005-0

  • eBook Packages: Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation