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Review

Relevance of radiobiological concepts in radionuclide therapy of cancer

, , , , &
Pages 173-186 | Received 04 Jun 2015, Accepted 08 Jan 2016, Published online: 26 Feb 2016
 

Abstract

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.

Abbreviations
ALL=

Acute Lymphoid Leukaemia

AML=

Acute Myeloid Leukaemia

CEA=

Carcinoembryonic Antigen

CD=

Cluster of Differentiation

CLL=

Chronic Lymphocytic Leukaemia

CNS=

Central Nervous System

CPP=

Cell Penetrating Peptide, DC, Dendritic Cell

DOTA=

1,4,7,10-Tetraazacyclododecane-1,4,7,10-Tetraacetic Acid

DTPA=

Diethylene Triamine Pentaacetic Acid

EDTMP=

Ethylenediamine Tetra(methylene Phosphonic Acid); EGFR, Epidermal Growth Factor Receptor

EU=

European Union

FDA=

Food and Drug Administration

Her2=

Human Epidermal Growth Factor Receptor 2

HEDP=

1-Hydroxy Ethylidene-1,1-Diphosphonic Acid

GI=

Gastro Intestinal

HLA=

Human Leukocyte Antigen

HRS=

Hyper-radiosensitivity

LET=

Linear Energy Transfer

MCL=

Mantle Cell Lymphoma

MIBG=

Metaiodobenzylguanidine

MN=

Micronuclie

4-NCS-Bz-TCMC=

S-2-(4-isothiocyanatobenzyl) -1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl) cyclododecane

NHL=

Non-Hodgkin’s Lymphoma

PSMA=

Prostate Specific Membrane Antigen

RGD=

Arginylglycylaspartic Acid

RIAR=

Radiation-Induced Adaptive Response

RIBE=

Radiation-Induced Bystander Effect

RIGI=

Radiation-Induced Genomic Instability

RNT=

Radionuclide Therapy

TAT=

Targeted Alpha Therapy

TATE=

Tyr3-octreotate

TIMP=

Tissue Inhibitor of Metalloproteinase

TOC=

Tyr3-octreotide

VEGF=

Vascular Endothelial Growth Factor.

Acknowledgements

Sejal Desai would like to acknowledge DAE Graduate Fellowship provided from Department of Atomic Energy, Government of India.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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