2. Introduction
● Also known as Targeted Radionuclide Therapy.
● Selective delivery of radionuclide to cancer cells using antibody or other
conjugate.
● FDA approved Radioimmunotherapy(RIT) using antibody or antibody derived
conjugates in the year 2000.
● Efficacy depends on a number of factors like properties of targeted antigen or
receptor,affinity and avidity of antibody and tumor factors like
vascularity,blood flow and permeability.
● Earlier murine immunoglobulin G(IgG) were used and due to fear of
immunogenicity of nonhuman antibodies,it was regarded as a serious
limitation of RIT,but now humanized and human monoclonal antibodies and
even non antibody carriers have been used.
3. ● Much of the pioneering work done in this field by Stanley Order and his
colleagues in 1980.
● Historically performed first for Hodgkins Lymphoma.
● Primary focus on antiferritin antibody labelled with radioactive iodine or
yttrium.
● Disadvantage of I-131 was large amount of radioactivity needed(30 mCi)
and had weak beta emission(0.3 Mev) as compared to yttrium-90 which
had pure beta emission of high energy(0.9 Mev) but indium-111 which is a
gamma emitter needed to be added to allow visualization which was not
the case in I-131 as it itself had gamma emission too.
● Nut die to availability of SPECT, it is no longer required to add gamma
emitters.
4. Radiobiology
● Biological effects of RIT depend both on the radionuclide as well as the
carrier.
● Some antibody themselves have antitumor efficacy like anti CD20
antibody.
● They can induce apoptosis,complement dependent cytotoxicity as well as
antibody dependent cytotoxicity which is very well useful in lymphomas.
● Solid tumors do not generally undergo apoptosis but they undergo
mitotic death.
● It works like Low Dose Rate (LDR) radiation which blocks cells in G2M
phase of cell cycle which makes them very much sensitive to radiation
induced cell killing known as inverse dose effect.
5. ● Can be combined with External Beam Radiotherapy,chemotherapy as well
as hyperthermia.
● Trials done so far have shown positive results.
● Most preferable results have been obtained in low tumor burden settings
like in case of subclinical or microscopic residual disease.
● Can be administered in fractionated setting by giving divided infusions in
space of days to weeks to minimize the normal tissue toxicity and take
advantage of difference in uptake and clearance kinetics of normal tissue
and tumor.
6. Combined approaches
★ RIT and Chemotherapy:Multiple preclinical studies have shown additive or
supra-additive effects with this combination including gemcitabine,taxanes,5-
FU,doxorubicin and anti EGFR antibody like Cetuximab and anti Her2 antibody
like Trastuzumab.
★ RIT and EBRT:Two modalities in combination would deliver a higher
cumulative dose of radiation to tumor and post EBRT, due to death of
cancerous cells increased expression of tumor antigen and increase in
vascular permeability of tumors due to reduction in tumor mass would
enhance the effects of RIT.
7. ★ RIT and Hyperthermia:It enhances the effect of RIT through increased
antigen expression,increase tumor blood flow and vascularity,decrease
tumor interstitial pressure and radiosensitization through inhibition of
sublethal and potentially lethal damage repair.
9. Clinical Uses
● Regional administration like intraperitoneal,intracavitary,intralesional and
intra-arterial to optimize uptake at tumor site to minimize normal tissue
toxicity.
● Done in cases of ovarian cancer,glioblastoma multiforme and other
gliomas.
● Hematological malignancies like relapsed or refractory low grade
lymphomas like B cell NHL and some T cell NHL and leukemias.
● Doses are of the order of 20 to 30 Gy.
10. Toxicities
● Bone marrow suppression has been the primary dose limiting toxicity.
● Acute symptoms are rather due to the antibody than the radionuclide
itself which includes fatigue,nausea,vomiting,headache,allergy,GI
disturbances.
● Steroids help in ameliorating these symptoms.
● Bladder toxicity has been the most severe one which can be decreased by
continuous irrigation during the therapy.
11. Dosimetry
● Complicated!
● Data are usually acquired by serial gamma camera imaging.
● TLD implantation inside the tumor cavity or biopsy of the tumor post
therapy can be done but are invasive procedures.
● Difficult due to inhomogeneous dose distribution.
12. ➔ RIT is a promising therapeutic modality and ongoing research work in this
area will lead to its improved efficacy.
