Healthcare applications of radioisotopes

Radioisotopes have several important applications in the field of medicine. The use of
a particular radioisotope for medical use depends upon its nuclear decay characteristics
(decay mode, decay energy, half life etc). If the nuclear characteristics are suitable, the next
stage is the mode of production (in nuclear reactors/accelerators). The availability of target
for irradiation is also an important criterion, as enriched targets are highly expensive. Not all
radioisotopes can be used for medical use. Radioisotopes for medical use are produced in
nuclear reactors as well as in accelerators (which include medical cyclotrons). Almost all the
radioisotopes which are currently in medical use are beta emitters and gamma emitters.
Recently an alpha emitter 225Ac is being used for cancer therapy.
Radioisotopes are used in sealed form (in teletherapy and brachytherapy in cancer
treatment) or as unsealed sources (radiopharmaceuticals) in nuclear medicine. Currently, the
radiopharmaceuticals which are produced and supplied by the Board of Radiation & Isotope
Technology (BRIT), DAE are prepared using radioisotopes produced in the Dhruva reactor of
BARC and processed at RPhD, BARC. Recently, APSARA reactor has also been
commissioned in BARC using which radioisotopes such as 64Cu can also be produced which
required high fast neutron flux.
External beam radiation therapy (Teletherapy) and brachytherapy are extensively used
for cancer treatment. Both use sealed sources of radiation. In teletherapy, radiations from an
external sealed source of radiation (Cobalt-60 as in Bhabhatron) are focussed on the patient’s
tumor to cause its killing. In this mode of therapy, the radiation dose is away from the patient.
The patient’s tumor is exposed to the radiations from the external source. BRIT has a
Regional Centre at KOTA, Rajasthan (near the RAPS) for the fabrication of 60Co sources
called RAPPCOF (Rajasthan Atomic Power Plant Cobalt Facility). X rays and gamma
radiation sources are being extensively used in the form of external beam therapy for cancer
cell killing. Recently, proton therapy is introduced in India for cancer treatment. Proton
therapy is another form of external beam therapy which makes use of high energy protons
produced in synchrotrons or cyclotrons. The high energy protons are directed to deposit on
the tumor thereby resulting in its destruction. An important advantage of proton beam therapy
is that the energy of the protons can be tuned in such a way that the proton beam strikes the
tumor which is located at a particular depth inside the body. This mode of therapy
significantly reduces the radiation dose to the normal cells. Proton therapy reportedly results
in less radiation dose to the normal cells than conventional external beam therapy using X
rays and 60Co sources. In India, proton therapy facility is available in few private hospitals
currently, but is highly expensive. In brachytherapy, the sealed source (in the form of wires,
seeds, plaque etc.) is kept in close contact with the tumor, either temporarily or permanently
depending on the type of cancer. The radioisotopes commonly used for brachytherapy are
Iridium-192 (192Ir), Iodine-125 (125I), Palladium-103 (103Pd), Ruthenium-106 (106Ru) etc.
Brachytherapy is commonly used for treatment of eye cancers, cancer of the cervix, prostate
cancer etc. Waste Management Group, BARC has recently launched a 106Ru plaque source
for treatment of eye cancers by brachytherapy.
Nuclear Medicine:
Nuclear medicine is a branch of medicine which utilizes radiopharmaceuticals for
diagnosis (diagnostic nuclear medicine) or treatment of diseases (therapeutic nuclear
medicine). Radiopharmaceuticals are special radiochemical formulations which are certified
to be safe for human administration. Usually a radiopharmaceutical consists of a radioisotope
which is linked to a vector (which can be a drug, particle, biomolecule etc.). In few cases,
simple radiochemical solutions are also used. For example, 131I-sodium iodide solution is
used for treatment of thyroid disorders (as iodine has affinity for thyroid), 89SrCl2 is used for
bone pain palliation as 89Sr is taken up by bone mistaking it as calcium, as strontium and
calcium have somewhat similar chemical properties, being elements belonging to the same
group.

Diagnostic radiopharmaceuticals:
Diagnostic nuclear medicine is a non-invasive imaging modality which utilizes
radiopharmaceuticals to diagnose diseases at very early stage as well as for the detection of
malfunctioning of various organs of the body. Diagnostic radiopharmaceuticals are also
routinely used to monitor response to therapy. Diagnostic radiopharmaceuticals make use of
gamma emitters or positron emitters tagged to suitable carrier. The requirements for a
radioisotope to be used for diagnosis are i) short-half life (few hours to few days) ii) Gamma
or positron emitter iii) No particulate emission means no emission of negatrons and alphas iv)
the gamma radiations emitted should be in the low energy range v) easy of availability
Gamma Emitters
The most common gamma emitter used in diagnostic nuclear medicine is
Technetium-99m (99mTc). 99mTc has a 6 h half life, it emits gamma radiations of 140 keV, it
is available from 99Mo/99mTc generator 99mTc is called as the workhorse of nuclear medicine.
When the generator (in which Molybdenum-99 is adsorbed on an alumina column) is eluted
with saline, the 99mTc elutes out as 99mTc does not have any affinity to the alumina. It is then
used to prepare 99mTc radiopharmaceuticals by tagging to suitable carrier. Different types of
cold kits (containing diverse ligands depending upon the disease/organ to be imaged) are
commercially available for labelling with 99mTc. In India, the Board of Radiation & Isotope
Technology (BRIT) (under DAE) supplies 99Mo/99mTc generators as well as the cold kits to
nuclear medicine centres all over India. BRIT is also executing a Fission Moly Project for the
production of 99Mo towards the production and supply of 99Mo/99mTc generators as currently
the 99Mo used is imported. More than 80 % of nuclear medicine is diagnostic nuclear
medicine. Table-1 represents the various cold kits available for preparation of 99mTc
radiopharmaceuticals.
 Table:1 : Cold kits for 99mTc radiopharmaceuticals

Kit for 99mTc radiopharmaceutical End Use

99m
Tc-MIBI;99mTc-Tetrofosmin Myocardial perfusion imaging

99m
Tc-MDP Bone imaging
99m
Tc-DTPA, 99mTc(III)-DMSA, 99m
Tc- Kidney function studies
EC, 99mTc-GHA
99m
Tc-Mebrofenin Hepatobiliary function studies
99m
Tc - Sulphur Colloid; 99mTc-Phytate Liver imaging
99m
Tc-ECD Brain perfusion imaging
99m
Tc-TRODAT Brain imaging
99m
Tc-HYNIC-TOC/ HYNIC-TATE Neuroendocrine tumor imaging
99m
Tc-MAA Lung perfusion imaging
99m
Tc-HSA Nanocolloid Sentinel lymph node imaging
99m
Tc(V)-DMSA Medullary thyroid carcinoma
99m
Tc-UBI Infection imaging

The 99Mo/99mTc generators as well as the cold kits are supplied to nuclear medicine
centres. The protocol for preparation of the 99mTc radiopharmaceuticals using the kit is also
provided along with the kit. The nuclear medicine centres then prepare the
radiopharmaceutical at their hospital radiopharmacy just before use in patients. Other gamma
emitters used for diagnostic radiopharmaceuticals include 201Tl, 123I etc. Currently, BRIT
does not supply 201Tl and 123I.
Positron Emitters:
Positron emitters are also used for disease detection and the corresponding imaging
modality is called Positron Emission Tomography. While gamma emitters are produced in
nuclear reactors or accelerators, positron emitters are produced exclusively in accelerators.
Medical cyclotrons are compact accelerators which are used for production of positron
emitting radioisotopes. The first medical cyclotron in India was established at Radiation
Medicine Centre, BARC in the year 2002. Subsequently, medical cyclotrons were established
by several private companies. There are more than 20 medical cyclotrons in India under the
private sector. Table-2 lists the positron emitters which are being used for PET imaging
applications.

Table-2: Positron emitters for PET imaging

Radioisotope Half Life E+(Max) (keV)

Oxygen-15 (15O) 2 min 1732
Nitrogen-13 (13N) 10 min 1199
Carbon-11 (11C) 20.4 min 960
Gallium-68 (68Ga) 67.7 min 1899
Fluorine-18 (18F) 110 min 634

Fluorine-18 is the most widely used positron emitter used in nuclear medicine due to
its suitable nuclear decay characteristics as well as its chemical properties. Fluorine-18
decays to stable 18O by the emission of positrons of maximum energy 635 keV (97 %
positron branching) with a half life of 109.9 minutes.
Fluorine-18 can be produced in medical cyclotrons by the bombardment of 18O
enriched water with high energy protons according to the reaction 18O(p,n)18F. Some of the
18
F radiopharmaceuticals of routine use are given in the following table. Among these, 18F-
FDG (18F-Fluorodeoxy glucose) is the most widely used for PET imaging and is called the
“molecule of the millennium”. The basis of PET imaging with FDG is the increased demand
for glucose exhibited by many cells including cancer cells. Hence, the increased uptake of
FDG can be attributed to this basic trait of cancer cells. Table-3 lists some 18F
radiopharmaceuticals and their applications.

Table-3: Few 18F radiopharmaceuticals and their end use

Product PET Imaging Application

18
F-FDG injection Oncology, neurology, cardiology
18
F-Sodium fluoride injection Bone imaging
18
F-Fluoro-thymidine injection Tumor imaging
18
F-Fluoro-Ethyl tyrosine injection Tumor imaging
18
F-Fluoro-Misonidazole injection Tumor imaging

Positron emitting radiopharmaceuticals are routinely produced using automated

synthesis modules unlike the 99mTc radiopharmaceuticals which are prepared using cold kits
and 99mTc from generator. Hence, the PET radiopharmaceuticals are produced and supplied
“ready for use” to hospitals. Gallium-68 is a positron emitter having 68 min. half life which is
available from 68Ge/68Ga generators. Hence, unlike 18F, it does not require a nearby cyclotron
for its production, although its parent 68Ge is cyclotron-produced. Gallium-68 labeled
peptides DOTATATE and PSMA-11 are used for PET based detection of neuroendocrine
tumors and prostate cancers respectively.
Once the diagnostic radiopharmaceutical is injected inside the patient by intravenous
injection, the patient is then imaged using a Single Photon Emission Computed Tomography
(SPECT) system (for gamma emitters) or Positron Emission Tomography (PET) system (for
positron emitters) which images the distribution of the radiopharmaceutical inside the
patient’s body. SPECT and PET are functional imaging techniques as they detect minute
changes in the underlying biochemical/physiological processes during disease progression.
These imaging technologies aid the early detection and staging of lesions. Both modalities
give 3D images of the distribution of the radiopharmaceutical injected to the patient. SPECT
system detects the single gamma ray emitted by the gamma emitter (for instance 99mTc) and
reconstructs a 3D image of the distribution inside the body with the help of computer
software. Decay of the positron emitter results in the emission of a positron which after
dissipating its energy combines with a nearby electron (annihilation) resulting in the emission
of two gamma rays at opposite directions (180) to each other. The coincident gamma rays
are detected by the PET detector. Most of the current SPECT and PET systems are integrated
with Computed Tomography (CT) units for precise and accurate diagnosis of abnormalities.
While the CT component provides anatomical image, SPECT/PET imaging provides
functional information about the lesion, the fused image assists the physician to exactly locate
the lesion.
PET radiopharmaceutical use has increased significantly in India. This can be gauged
from the number of PET-CT systems installed which come to greater than 250. The 30 MeV
Cyclon-30 medical cyclotron became operational at VECC Kolkata last year. This cyclotron
is operated by BRIT Regional Centre at Kolkata along with VECC. It has started regular
production and supply of 18F-FDG to nuclear medicine centres in Kolkata. There are plans for
the regular production of radioisotopes such as 68Ge, 68Ga, 201Tl, 123I etc.

Therapeutic radiopharmaceuticals
Therapeutic radiopharmaceuticals are also used for treatment of diseases, especially
cancer. Therapeutic radiopharmaceuticals utilize β- emitting radioisotopes or  emitters as the
purpose here is to selectively kill the cancer cells. The radioisotopes used for the purpose
should have suitable nuclear decay characteristics as well as chemical properties. Almost all
the therapeutic radiopharmaceuticals used till date make use of β- emitters. Iodine-131
radiopharmaceuticals (for thyroid cancer and thyroid related disorders) comprise the
maximum used therapeutic radiopharmaceuticals while Lutetium-177 labeled
radiopharmaceuticals come next. Other β- emitters used include 153Sm, 90Y etc.
 Radioisotope Half Emax(MeV) E(keV) Production Method
life
130
Iodine-131 8d 0.606 (89%) 364 Te target (neutron irradiation)
(81%)
90
Yttrium-90 64.1 h 2.28 (100%) - Sr/90Y generator
90
Sr is a fission product
176
Lutetium-177 6.9 d 0.497 (76%) 208 Lu(n,γ)177Lu – currently used
(11%) production route in BARC
176
Yb(n,γ)177Yb
177
Yb decays to 177Lu by β- emission

Apart from 131I radiopharmaceuticals (oral solution and capsules) which are supplied
to nuclear medicine centres spanning all over India, 177Lu labelled radiopharmaceuticals are
also supplied by BRIT. This includes 177Lu-DOTATATE (therapy of neuroendocrine
tumors), 177Lu-PSMA-617 (therapy of prostate cancers) and 177Lu-EDTMP (for bone pain
palliation). 153Sm-EDTMP is also produced and supplied for bone pain palliation in cancer
patients. There are reports on the production of 89SrCl2 at FBTR, Kalpakkam towards bone
pain palliation.
A recent development is the use of alpha emitter 225Ac for therapy. 225Ac has a half
life of 9.9 days and emits several alphas of suitable energy during its decay. 225Ac-PSMA is
being used in many countries for treatment of prostate cancers. Large scale production
underway in countries including USA and Canada.

DOTATATE : DOTA-3Tyr-Octreotide wherein DOTA is the bifunctional chelator (linker)

linking Lutetium-177 to the peptide (3Tyr-Octreotide)
PSMA : Prostate Specific Membrane Antigen
EDTMP :Ethylene diamine tetramethylene phosphonic acid

Other Applications in healthcare

Radioimmunoassay (RIA) and Immunoradiometric assay (IRMA)
RIA and IRMA are in vitro diagnostic techniques which are mainly being used for the
determination of concentrations of various hormones in blood. These techniques were
extensively used till the 1990s for the purpose and are now replaced by
chemiluminescence/fluorescence based techniques. BRIT supplies RIA and IRMA kits for
the detection of thyroid hormones in blood. These techniques use the radioisotope Iodine-125
in very small quantities.
Sterilisation of medical products
Sealed radioactive sources such as 60Co are also used for the sterilisation of medical
products. ISOMED plant (under BRIT) was set up in BARC, Trombay premises in 1974 to
sterilize medical and herbal products which uses 60Co source (1000 KiloCi). The plant is
currently under refurbishment.