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Clinical application of radioiodinated antibodies: where are we?

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Abstract

Eradication of cancer still remains an upsetting issue despite our increased understanding of the molecular basis of carcinogenesis. Factors such as the molecular heterogeneity of some tumours and initial diagnosis at advanced stages hamper effective disease treatment. Given the ineffectiveness of current treatments, the development of newer therapeutic modalities to address clinical unmet needs is still mandatory. Radioimmunotherapy (RIT) that combines the use of specific antibodies against tumour-associated antigens with the cytotoxic properties of therapeutic radionuclides is amongst those approaches. The potential of monoclonal antibodies to complement current treatment protocols may bring a significant improvement to the overall therapeutic outcomes of oncologic disorders. RIT permits the delivery of a high dose of therapeutic radiation to cancer cells, while minimizing the exposure of normal cells. 131I and 90Y have been used in > 95% of clinical RIT trials and represent the current standard to which all other radionuclides are compared. Both β-particle-emitting isotopes qualify for RIT because of their favourable emission characteristics and availability and flexible radiochemistry. The importance of radioiodine in nuclear medicine together with the success of radioiodinated antibody-based drugs in the clinical setup prompted us to provide an updated overview of the application of radioiodinated antibodies in RIT and anticipate potential relevant accomplishments in the near future.

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Abbreviations

L8A4:

EGFRvIII-targeting monoclonal antibodies

Hepama-1:

Anti-HCC monoclonal antibody

L6:

Tumour-associated antigen

[125I]-SGMIB:

N-succinimidyl 4-guanidinomethyl-3-[125I]iodobenzoate

131I-chTNT-1/B mAb:

Cotara®

131I-ERIC-1:

Labelled monoclonal antibody against NCAM

131I-L19SIP:

Radretumab

131I-UJ13A:

Labelled monoclonal antibody against NCAM

18F-FDG:

18F-fluorodeoxyglucose

3F8:

Murine monoclonal IgG3 antibody against GD2

A33 antigen:

Transmembrane protein expressed almost exclusively by intestinal epithelial cells

AFP:

Alpha-fetoprotein

alpha-IFN:

Alpha interferon

ASCO:

American Society of Clinical Oncology

B72.3:

Monoclonal anti-TAG-72 antibody

BC:

Breast cancer

BC-2, BC-4, 81C6, ST2146, ST2485, F16, P12:

Murine antibodies against tenascin-C

BT-474:

Human breast carcinoma cell line (HER2+, ER+)

BTD:

Breakthrough therapy designation

c, ch :

Chimeric

C5:

Complement protein

CA125:

Cancer antigen 125

CaPan1:

Human pancreatic ductal adenocarcinoma cell line

CC49:

Monoclonal anti-TAG-72 antibody

CD:

Cluster of differentiation

CDR:

Complementarity-determining region

CEA:

Carcinoembryonic antigen

CED:

Convection-enhanced delivery

ch81C6:

Chimeric antibody against tenascin-C

CHOP:

Cyclophosphamide-Adriamycin-Oncovin-prednisone

CLM:

Colorectal liver metastasis

COL-1:

Monoclonal antibody specific for CEA

CR:

Complete response

CRC:

Colorectal cancer

cRIT:

Compartmental radioimmunotherapy

CT:

Computed tomography

CTV:

Clinical target volume

CVP:

Cyclophosphamide–vincristine–prednisolone

DLBCL:

Diffuse large B-cell lymphoma

DLT:

Dose-limiting toxicity

DNA:

Deoxyribonucleic acid

EDB:

Extra domain B of fibronectin

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMA:

European Medicines Agency

EpCAM, KSA, KS1/4 or 17–1 antigen:

Epithelial cell adhesion molecule

F(ab′), F(ab′)2:

Antibody fragments

FA8H1:

Murine–human anti-VEGFR2 chimeric Fab

FDA:

Food and Drug Administration

FL:

Follicular lymphoma

FN:

Fibronectin

GBM:

Glioblastoma multiforme

GD2:

Disialoganglioside

GLOBOCAN:

Global cancer incidence, mortality and prevalence

GP38:

Glycoprotein 38

GSK:

Glaxo Smith Kline

HAb18G/CD147:

Hepatocellular carcinoma-associated antigen

HAMA:

Human anti-murine antibody

HACA:

Human anti-chimeric antibody

HCC:

Hepatocellular carcinoma

HER2:

Human epidermal growth factor receptor 2

HMFG:

Human milk fat globule

IgE, IgG:

Immunoglobulin

IL:

Interleukin

ic:

Intracavitary

ip:

Intraperitoneal

it:

Intratumoural

iv:

Intravenous

kDa:

Kilodalton

LNCaP cells:

Androgen-sensitive human prostate adenocarcinoma cells

LQC:

Last qualifying chemotherapy

LS-174 T:

Human colon cancer cell line

m :

Murine

MA:

Meconium antigen

mAb:

Monoclonal antibody

mAb806:

EGFRvIII-targeting monoclonal antibodies

mCRPC:

Metastatic castration-resistant prostate cancer

MDA-MB-453:

Breast cancer cell line (AR+, ER−, PR−, HER2/neu−)

MG:

Malignant glioma

MOv:

Murine monoclonal antibody against the epitope of human folate-binding protein

MSKCC:

Memorial Sloan Kettering Cancer Center

MTD:

Maximum tolerated dose

MUC:

Mucin

NCA:

Nonspecific cross-reacting antigen

NCAM:

Neural cell adhesion molecule

NED:

No evidence of disease

NHL:

Non-Hodgkin’s lymphoma

NP:

Antibody against CEA

OC:

Ovarian cancer

OC125:

Murine monoclonal antibody that recognizes the antigenic determinant CA125

OS:

Overall survival

PAM4:

Monoclonal antibody with high specificity for pancreatic ductal adenocarcinoma

PD1:

Programmed cell death protein

PET:

Positron emission tomography

PFS:

Progression-free survival

PLAP:

Placental alkaline phosphatase

PR:

Partial remission

PSA:

Prostate-specific antigen

PSMA:

Prostate-specific membrane antigen

rec:

Recombinant

RIS:

Radioimmunoscintigraphy

RIT:

Radioimmunotherapy

RSV:

Respiratory syncytial virus

scFv:

Single-chain variable fragment

SCRC:

Surgery-created resection cavities

SIP:

Small immunoprotein

SPECT:

Single-photon emission computed tomography

SWOG:

Southwest Oncology Group

TAG-72:

Tumour-associated glycoprotein 72

TNF:

Tumour necrosis factor

TNT:

Tumour necrosis therapy

VEGF:

Vascular endothelial growth factor

WBRT:

Whole brain radiation treatment

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Funding

This study was partially supported by Fundação para a Ciência e Tecnologia (UID/Multi/04349/2020 and PTDC/QUINUC/30147/2017.)

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  1. Departamento de Engenharia e Ciências Nucleares (DECN) e Centro de Ciências e Tecnologias Nucleares (C2TN), Instituto Superior Técnico, Universidade de Lisboa, CTN, Estrada Nacional 10 (km 139,7), 2695-066, Bobadela, LRS, Portugal

    Maria Cristina Oliveira & João D. G. Correia

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  1. Maria Cristina Oliveira
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  2. João D. G. Correia
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Both authors, M-CNO and JDGC, have contributed equally to the conceptualization, writing, review and editing of this manuscript.

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Oliveira, M.C., Correia, J.D.G. Clinical application of radioiodinated antibodies: where are we?. Clin Transl Imaging 10, 123–162 (2022). https://doi.org/10.1007/s40336-021-00477-2

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