Relevance of radiobiological concepts in radionuclide therapy of cancer

Purpose Radionuclide therapy (RNT) is a rapidly growing area of clinical nuclear medicine, wherein radionuclides are employed to deliver cytotoxic dose of radiation to the diseased cells/tissues. During RNT, radionuclides are either directly administered or delivered through biomolecules targeting the diseased site. RNT has been clinically used for diverse range of diseases including cancer, which is the focus of the review.Conclusions The major emphasis in RNT has so far been given towards developing peptides/antibodies and other molecules to conjugate a variety of therapeutic radioisotopes for improved targeting/delivery of radiation dose to the tumor cells. Despite that, many of the RNT approaches have not achieved their desired therapeutic success probably due to poor knowledge about complex and dynamic (i) fate of radiolabeled molecules; (ii) radiation dose delivered; (iii) cellular heterogeneity in tumor mass; and (iv) cellular radiobiological response. Based on understanding gathered during recent years, it may be stated that besides the absorbed dose, the net radiobiological response of tumor/normal cells also determines the clinical response of radiotherapeutic modalities including RNT. The radiosensitivity of tumor/normal cells is governed by radiobiological phenomenon such as radiation-induced bystander effect, genomic instability, adaptive response and low dose hyper-radiosensitivity. These concepts have been well investigated in the context of external beam radiotherapy, but their clinical implications during RNT have received meagre attention. In this direction, a few studies performed using in vitro and in vivo models envisage the possibilities of exploiting the radiobiological knowledge for improved therapeutic outcome of RNT.AbbreviationsALLAcute Lymphoid LeukaemiaAMLAcute Myeloid LeukaemiaCEACarcinoembryonic AntigenCDCluster of DifferentiationCLLChronic Lymphocytic LeukaemiaCNSCentral Nervous SystemCPPCell Penetrating Peptide, DC, Dendritic CellDOTA1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic AcidDTPADiethylene Triamine Pentaacetic AcidEDTMPEthylenediamine Tetra(methylene Phosphonic Acid); EGFR, Epidermal Growth Factor ReceptorEUEuropean UnionFDAFood and Drug AdministrationHer2Human Epidermal Growth Factor Receptor 2HEDP1-Hydroxy Ethylidene-1,1-Diphosphonic AcidGIGastro IntestinalHLAHuman Leukocyte AntigenHRSHyper-radiosensitivityLETLinear Energy TransferMCLMantle Cell LymphomaMIBGMetaiodobenzylguanidineMNMicronuclie4-NCS-Bz-TCMCS-2-(4-isothiocyanatobenzyl) -1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl) cyclododecaneNHLNon-Hodgkin’s LymphomaPSMAProstate Specific Membrane AntigenRGDArginylglycylaspartic AcidRIARRadiation-Induced Adaptive ResponseRIBERadiation-Induced Bystander EffectRIGIRadiation-Induced Genomic InstabilityRNTRadionuclide TherapyTATTargeted Alpha TherapyTATETyr3-octreotateTIMPTissue Inhibitor of MetalloproteinaseTOCTyr3-octreotideVEGFVascular Endothelial Growth Factor.