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Current Cancer Therapy Reviews


ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Applications of Radiopharmaceuticals in the Treatment of Cancer: Recent Developments

Author(s): Priyanshi Goyal and Rishabha Malviya*

Volume 20, Issue 2, 2024

Published on: 07 September, 2023

Page: [154 - 165] Pages: 12

DOI: 10.2174/1573394719666230717103228

Price: $65


An emerging safe and efficient targeted method of treating many different types of cancer is radiopharmaceutical treatment (RPT). RPT uses medications that either bind more selectively to cancer cells or accumulate through physiological processes to deliver radiation either systemically or locally. Nearly all radionuclides employed in RPT generate imageable photons, allowing for noninvasive visualization of the therapeutic agent's biodistribution. RPT has demonstrated efficacy with little toxicity when compared to practically all other systemic cancer treatment approaches. The tremendous potential of this treatment is finally being acknowledged as a result of the FDA's recent approval of many RPT medicines. The fundamental characteristics, clinical advancement, and related difficulties of RPT are covered in this review.

Keywords: Cancer, radiation therapy, cell cycle, radiopharmaceuticals, targeted therapy, cyclin-dependent kinases.

Graphical Abstract
GLOBOCAN. 2008, Cancer incidence and mortality worldwide. Lyon, France: IARC 2010.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61(2): 69-90.
[] [PMID: 21296855]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12): 2893-917.
[] [PMID: 21351269]
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57-70.
[] [PMID: 10647931]
Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011; 331(6024): 1559-64.
[] [PMID: 21436443]
von Sonntag C. Free-radical-induced DNA Damage and its Repair. Berlin, Heidelberg: Springer 2006.
Baserga R. Ed The Cell Cycle and Cancer. New York: Dekker 1971; p. 1.
Quastler H, Sherman FG. Cell population kinetics in the intestinal epithelium of the mouse. Exp Cell Res 1959; 17(3): 420-38.
[] [PMID: 13672199]
Baserga R. Cell Tissue Kinet 1968; 1: 167.
Hill BT, Symington T, Carter R. Scientific foundations of oncology. W. Heinemann (Medical), London 1975.
The science behind radiation therapy. Available from:
Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 2009; 461(7267): 1071-8.
[] [PMID: 19847258]
Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 2011; 11(4): 239-53.
[] [PMID: 21430696]
External Beam Therapy (EBT) 2019. Available from:
Brachytherapy. 2019. Available from:
Introduction to cancer therapy (radiation oncology). 2019. Available from:
Hall EJ. Cancer caused by x-rays-a random event? Lancet Oncol 2007; 8(5): 369-70.
[] [PMID: 17466892]
Baskar R. Emerging role of radiation induced bystander effects: Cell communications and carcinogenesis. Genome Integr 2010; 1(1): 13.
[] [PMID: 20831828]
Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991; 21(1): 109-22.
[] [PMID: 2032882]
Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: current advances and future directions. Int J Med Sci 2012; 9(3): 193-9.
[] [PMID: 22408567]
Mohammad Bagher A, Vahid M, Mohsen M. Introduction to radioactive materials. Int J Renew Sustain Energy 2014; 3(3): 59-67.
Goggen TJ. Physical aspects of brachytherapy. (1st ed.). CRC Press 1988; p. 304.
Rostelato MECM. Physical aspects of brachytherapy. In: Radiation Oncology Physics:A Handbook for Teachers and Students. Sao Paulo: IPEN/USP 1997.
Rostelato MECM, Silva CPG, Rela PR, Zeituni CA, Lepki V, Feher A. Research reactor application to Iridium-192 production for cancer treatment. PHYSOR 2004 -The Physics of Fuel Cycles and Advanced Nuclear Systems: Global Developments. Chicago, Illinois. American Nuclear Society 2004.April 25-29, 2004
Russel J. A century of brachytherapy. Nucl News 2004; 47: 44-6.
Cardoso RM, de Souza CD, Rostelato MECM, Araki K. Highly efficient method for production of radioactive silver seed cores for brachy-therapy. Appl Radiat Isot 2017; 120: 76-81.
[] [PMID: 27918920]
Zeituni CA, Souza CD, Moura ES, et al. Theoretical, manufacturing and clinical application aspects of a prostate brachytherapy I-125 source in Brazil. BRACHYTHERAPY InTech. Rijeka: Croacia 2012; p. 17.
Goldner G, Pötter R, Battermann JJ, et al. Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients. Strahlenther Onkol 2012; 188(4): 305-10.
[] [PMID: 22349713]
Chodak G. Prostate brachytherapy has good long-term outcomes 2014. Available from:
Daruich de Souza C. Brachytherapy with seeds of iodine-125: Manufacture and treatment. Institute of biosciences, São Paulo State University 2009. Available from:
Lawrence DC. Therapeutic metal seed containing within a radioactive isotope disposed on a carrier and method of manufacture. Hazleton Nuclear Science Corporation 1967.
Andrews GA, Root SW, Kerman HD, Bigelow RR. Intracavitary colloidal radiogold in the treatment of effusions caused by malignant neo-plasms. Ann Surg 1953; 137(3): 375-81.
[] [PMID: 13031468]
Wheeler HB, Jaques W, Botsford TW. Experiences with the use of radioactive colloidal gold in the treatment of cancer. Ann Surg 1955; 141(2): 208-17.
[] [PMID: 13229255]
Buchsbaum HJ, Keettel WC. Radioisotopes in treatment of stage Ia ovarian cancer. Natl Cancer Inst Monogr 1975; 42: 127-8.
[PMID: 1234628]
Rogoff EE, Romano R, Hahn EW. The prevention of Ehrlich ascites tumor using intraperitoneal colloidal 198Au. Dose vs. size of inoculum. Radiology 1975; 114(1): 225-6.
[] [PMID: 1208864]
Bhattacharya R, Mukherjee P. Biological properties of “naked” metal nanoparticles. Adv Drug Deliv Rev 2008; 60(11): 1289-306.
[] [PMID: 18501989]
Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 2006; 79(939): 248-53.
[] [PMID: 16498039]
Chanda N, Kan P, Watkinson LD, et al. Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-198AuNP nanoconstruct in prostate tumor–bearing mice. Nanomedicine 2010; 6(2): 201-9.
[] [PMID: 19914401]
Diagaradjane P, Shetty A, Wang JC, et al. Modulation of in vivo tumor radiation response via gold nanoshell-mediated vascular-focused hyperthermia: characterizing an integrated antihypoxic and localized vascular disrupting targeting strategy. Nano Lett 2008; 8(5): 1492-500.
[] [PMID: 18412402]
Häfeli UO, Warburton MC, Landau U. Electrodeposition of radioactive rhenium onto stents to prevent restenosis. Biomaterials 1998; 19(10): 925-33.
[] [PMID: 9690834]
ICRU Report 50, prescribing, recording, and reporting photon beam therapy. 1999. Available from:
Feng FY, Kim HM, Lyden TH, et al. Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 2007; 68(5): 1289-98.
[] [PMID: 17560051]
Wang-Chesebro A, Xia P, Coleman J, Akazawa C, Roach M III. Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2006; 66(3): 654-62.
[] [PMID: 17011444]
Mundt AJ, Lujan AE, Rotmensch J, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002; 52(5): 1330-7.
[] [PMID: 11955746]
Langen KM, Jones DTL. Organ motion and its management. Int J Radiat Oncol Biol Phys 2001; 50(1): 265-78.
[] [PMID: 11316572]
Jaffray DA, Siewerdsen JH, Wong JW, Martinez AA. Flat-panel cone-beam computed tomography for image-guided radiation therapy. Int J Radiat Oncol Biol Phys 2002; 53(5): 1337-49.
[] [PMID: 12128137]
radiotherapy. Radiat Oncol. 2011; 6:145. 23. Duma MN, Kampfer S, Wilkens JJ, Schuster T, Molls M, Geinitz H. Comparative analysis of an image-guided versus a non-image-guided setup approach in terms of delivered dose to the parotid glands in head-and-neck cancer IMRT. Int J Radiat Oncol Biol Phys 2010; 77: 1266-73.
Barney BM, Lee RJ, Handrahan D, Welsh KT, Cook JT, Sause WT. Image-guided radiotherapy (IGRT) for prostate cancer comparing kV imaging of fiducial markers with cone beam computed tomography (CBCT). Int J Radiat Oncol Biol Phys 2011; 80(1): 301-5.
[] [PMID: 20864274]
Gill S, Thomas J, Fox C, et al. Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy. Radiat Oncol 2011; 6(1): 145.
[] [PMID: 22035354]
Lo SS, Fakiris AJ, Chang EL, et al. Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol 2010; 7(1): 44-54.
[] [PMID: 19997074]
Tipton K, Launders JH, Inamdar R, Miyamoto C, Schoelles K. Stereotactic body radiation therapy: scope of the literature. Ann Intern Med 2011; 154(11): 737-45.
[] [PMID: 21536933]
Lo SS, Moffatt-Bruce SD, Dawson LA, et al. The role of local therapy in the management of lung and liver oligometastases. Nat Rev Clin Oncol 2011; 8(7): 405-16.
[] [PMID: 21606970]
Wu QJ, Thongphiew D, Wang Z, Chankong V, Yin FF. The impact of respiratory motion and treatment technique on stereotactic body radiation therapy for liver cancer. Med Phys 2008; 35(4): 1440-51.
[] [PMID: 18491539]
Image Guided Radiotherapy (IGRT); Guidance for implementation and use. 2012. Available from: file:///C:/Users/IT-ITS-047/Downloads/National%20Radiotherapy%20Implementation%20Group%20Report%20IGRT%20Final.pdf_1.pdf
Freeman DE, King CR. Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes. Radiat Oncol 2011; 6(1): 3.
[] [PMID: 21219625]
Pascu S, Dilworth J. Recent developments in PET and SPECT imaging. J Labelled Comp Radiopharm 2014; 57(4): 191-4.
[] [PMID: 24737125]
Keresztes A, Borics A, Tömböly C. Therapeutic and diagnostic radiopharmaceuticals. 2015. Available from:
Drozdovitch V, Brill AB, Callahan RJ, et al. Use of radiopharmaceuticals in diagnostic nuclear medicine in the United States: 1960-2010. Health Phys 2015; 108(5): 520-37.
[] [PMID: 25811150]
Laudicella R, Baratto L, Minutoli F, Baldari S, Iagaru A. Malignant cutaneous melanoma: updates in PET imaging. Curr Radiopharm 2020; 13(1): 14-23.
[] [PMID: 31749439]
Fang W, Liu S. New 99mTc radiotracers for myocardial perfusion imaging by SPECT. Curr Radiopharm 2019; 12(3): 171-86.
[] [PMID: 30727939]
Zhang XM, Zhang HH, McLeroth P, et al. [124I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection. Nucl Med Biol 2016; 43(5): 273-9.
[] [PMID: 27150029]
Fan D, Wang K, Gao H, et al. A 64 Cu-porphyrin-based dual-modal molecular probe with integrin α v β 3 targeting function for tumour imaging. J Labelled Comp Radiopharm 2020; 63(5): 212-21.
[] [PMID: 32083750]
Sager O, Dincoglan F, Demiral S, et al. Utility of molecular imaging with 2-deoxy-2-[fluorine-18] fluoro-dglucose positron emission tomography (18F-FDG PET) for Small cell lung cancer (SCLC): a radiation oncology perspective. Curr Radiopharm 2019; 12(1): 4-10.
[] [PMID: 30465520]
Kostenikov NA, Zhuikov BL, Chudakov VM, et al. Application of 82 Sr/82 Rb generator in neurooncology. Brain Behav 2019; 9(3): e01212.
[] [PMID: 30729720]
Carollo A, Papi S, Grana CM, Mansi L, Chinol M. State of the art and recent developments of radiopharmaceuticals for pancreatic neuroendocrine tumors imaging. Curr Radiopharm 2019; 12(2): 107-25.
[] [PMID: 30843499]
Shi S, Zhang L, Wu Z, et al. [68Ga]Ga-HBED-CC-DiAsp: A new renal function imaging agent. Nucl Med Biol 2020; 82-83: 17-24.
[] [PMID: 31869735]
Ilyushenkova J, Sazonova S, Zavadovsky K, et al. Diagnostic efficacy of cardiac scintigraphy with 99mtc-pyrophosphate for latent myocardial inflammation in patients with atrial fibrillation. Cardiol Res Pract 2020; 2020: 1-11.
[] [PMID: 32211203]
Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. J Immunol Res 2016; 2016: 1-13.
[] [PMID: 26885535]
Biaoxue R, Xiguang C, Shuanying Y. Annexin A1 in malignant tumors: current opinions and controversies. Int J Biol Markers 2014; 29(1): e8-e20.
[] [PMID: 24242295]
Chen F, Madajewski B, Ma K, et al. Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles. Sci Adv 2019; 5(12): eaax5208.
[] [PMID: 31840066]
Chen F, Xiao Y, Shao K, Zhu B, Jiang M. Positron emission tomography imaging of a novel Anxa1-targeted peptide 18 F-Al-NODA-Bn-p-SCN-GGGRDN-IF7 in A431 cancer mouse models. J Labelled Comp Radiopharm 2020; 63(12): 494-501.
[] [PMID: 32562502]
Shamsel-Din HA, Gizawy MA, Zaki EG, Elgendy A. A novel 99m Tc-diester complex as tumor targeting agent: Synthesis, radiolabeling, and biological distribution study. J Labelled Comp Radiopharm 2020; 63(8): 376-85.
[] [PMID: 32335935]
Ercan MT, Caglar M. Therapeutic radiopharmaceuticals. Curr Pharm Des 2000; 6(11): 1085-121.
[PMID: 10903384]
Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 2014; 66: 2-25.
[] [PMID: 24270007]
Yeong CH, Cheng M, Ng KH. Therapeutic radionuclides in nuclear medicine: current and future prospects. J Zhejiang Univ Sci B 2014; 15(10): 845-63.
[] [PMID: 25294374]
D'angelo G, Sciuto R, Salvatori M, et al. Targeted “bone-seeking” radiopharmaceuticals for palliative treatment of bone metastases: A systematic review and meta-analysis. Q J Nucl Med Mol Imaging 2012; 56(6): 538-43.
[PMID: 23358407]
Lange R, ter Heine R, Knapp RFF, de Klerk JMH, Bloemendal HJ, Hendrikse NH. Pharmaceutical and clinical development of phospho-nate-based radiopharmaceuticals for the targeted treatment of bone metastases. Bone 2016; 91: 159-79.
[] [PMID: 27496068]
Alsadik S, Yusuf S. AL-Nahhas A. Peptide receptor radionuclide therapy for pancreatic neuroendocrine tumours. Curr Radiopharm 2019; 12(2): 126-34.
[] [PMID: 30714538]
Incerti E, Gangemi V, Mapelli P, et al. 11C-Choline PET/CT based helical tomotherapy as treatment approach for bone metastases in re-current prostate cancer patients. Curr Radiopharm 2017; 10(3): 195-202.
[PMID: 28933270]
Morgenstern A, Apostolidis C, Kratochwil C, Sathekge M, Krolicki L, Bruchertseifer F. An overview of targeted alpha therapy with 225Actinium and 213Bismuth. Curr Radiopharm 2018; 11(3): 200-8.
[] [PMID: 29732998]
Camacho X, Calzada V, Fernandez M, et al. 177Lu-DOTA-Bevacizumab: Radioimmunotherapy agent for melanoma. Curr Radiopharm 2017; 10(1): 21-8.
[] [PMID: 27748184]
Wu L, Shen F, Xia Y, Yang YF. Evolving role of radiopharmaceuticals in hepatocellular carcinoma treatment. Anticancer Agents Med Chem 2016; 16(9): 1155-65.
[] [PMID: 26961314]
Cives M, Strosberg J. Radionuclide therapy for neuroendocrine tumors. Curr Oncol Rep 2017; 19(2): 9.
[] [PMID: 28220446]
Zhang J, Wang H, Jacobson O, et al. Safety, pharmacokinetics, and dosimetry of a long-acting radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in patients with advanced metastatic neuroendocrine tumors. J Nucl Med 2018; 59(11): 1699-705.
[] [PMID: 29653971]
Hagemann UB, Ellingsen C, Schuhmacher J, et al. Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers. Clin Cancer Res 2019; 25(15): 4723-34.
[] [PMID: 31064781]
Khawar A, Eppard E, Roesch F, et al. Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results. EJNMMI Res 2019; 9(1): 102.
[] [PMID: 31781962]
Tesson M, Rae C, Nixon C, Babich JW, Mairs RJ. Preliminary evaluation of prostate-targeted radiotherapy using 131I-MIP-1095 in combination with radiosensitising chemotherapeutic drugs. J Pharm Pharmacol 2016; 68(7): 912-21.
[] [PMID: 27139157]
Banerjee S, Pillai MRA, Knapp FFR. Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications. Chem Rev 2015; 115(8): 2934-74.
[] [PMID: 25865818]
Kolenc Peitl P, Rangger C, Garnuszek P, et al. Clinical translation of theranostic radiopharmaceuticals: Current regulatory status and recent examples. J Labelled Comp Radiopharm 2019; 62(10): 673-83.
[] [PMID: 30741441]
Turner JH. Recent advances in theranostics and challenges for the future. Br J Radiol 2018; 91(1091): 20170893.
[] [PMID: 29565650]
Choudhury P, Gupta M. Personalized & precision medicine in cancer: a theranostic approach. Curr Radiopharm 2017; 10(3): 166-70.
[PMID: 28758574]
Langbein T, Weber WA, Eiber M. Future of theranostics: an outlook on precision oncology in nuclear medicine. J Nucl Med 2019; 60(2) (Suppl. 2): 13S-9S.
[] [PMID: 31481583]
Jadvar H, Chen X, Cai W, Mahmood U. Radiotheranostics in cancer diagnosis and management. Radiology 2018; 286(2): 388-400.
[] [PMID: 29356634]
Boschi A, Martini P, Janevik-Ivanovska E, Duatti A. The emerging role of copper-64 radiopharmaceuticals as cancer theranostics. Drug Discov Today 2018; 23(8): 1489-501.
[] [PMID: 29635027]
Keinänen O, Brennan JM, Membreno R, et al. Dual radionuclide theranostic pretargeting. Mol Pharm 2019; 16(10): 4416-21.
[] [PMID: 31483993]
Ballinger JR. Theranostic radiopharmaceuticals: established agents in current use. Br J Radiol 2018; 91(1091): 20170969.
[] [PMID: 29474096]
Vimalnath KV, Rajeswari A, Sarma HD, Dash A, Chakraborty S. Ce-141-labeled DOTMP: A theranostic option in management of pain due to skeletal metastases. J Labelled Comp Radiopharm 2019; 62(4): 178-89.
[] [PMID: 30663098]
Galiè M, Boschi F, Scambi I, et al. Theranostic role of 32P-ATP as radiopharmaceutical for the induction of massive cell death within avascular tumor core. Theranostics 2017; 7(18): 4399-409.
[] [PMID: 29158835]
Lepareur N, Lacoeuille F, Bouvry C, et al. Rhenium-188 labeled radiopharmaceuticals: current clinical applications in oncology and promising perspectives. Front Med (Lausanne) 2019; 6: 132.
[] [PMID: 31259173]
Kortylewicz ZP, Coulter DW, Han G, Baranowska-Kortylewicz J. Radiolabeled (R)-(-)-5-iodo-3′- O -[2-(ε-guanidinohexanoyl)-2-phenylacetyl]-2′-deoxyuridine: A new theranostic for neuroblastoma. J Labelled Comp Radiopharm 2020; 63(7): 312-24.
[] [PMID: 32150284]
Cimini A, Ricci M, Chiaravalloti A, Filippi L, Schillaci O. Theragnostic aspects and radioimmunotherapy in pediatric tumors. Int J Mol Sci 2020; 21(11): 3849.
[] [PMID: 32481723]
Berenson A. Market forces cited in lymphoma drugs’ disuse. 2007. Available from:
Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics 2019; 20(2): 273-86.
[] [PMID: 29394327]
Lin A, Giuliano CJ, Palladino A, et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci Transl Med 2019; 11(509): eaaw8412.
[] [PMID: 31511426]
Mercadante S, Fulfaro F. Management of painful bone metastases. Curr Opin Oncol 2007; 19(4): 308-14.
[] [PMID: 17545792]
John KUS. DOE tri-lab production effort to provide accelerator-produced 225Ac for radiotherapy: 2019 update. J Nucl Med 2019; 60: 1612.
Hoehr C, Bénard F, Buckley K, et al. Medical isotope production at TRIUMF–from imaging to treatment. Phys Procedia 2017; 90: 200-8.
Karimian A, Ji NT, Song H, Sgouros G. Mathematical modeling of preclinical alpha-emitter radiopharmaceutical therapy. Cancer Res 2020; 80(4): 868-76.
[] [PMID: 31772036]
Kaushik D, Jangra P, Verma R, et al. Radiopharmaceuticals: An insight into the latest advances in medical uses and regulatory perspectives. J Biosci 2021; 46(1): 27.
[] [PMID: 33753578]

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