India, with a population of over 130 crore people has had to bear its share of misery and
despair caused by cancer - every year, 7 lakh new cases are registered in our country, and
more than 70% of these cases die because of late detection. Many cases are not even
registered because of the speed of the disease.
When detected early, localized cancers can be managed and treated. They can be surgically
excised, and the patients can be regularly monitored.
PET-CT is a state of the art imaging technology that allows for screening, diagnosis and
monitoring of cancer and helps in improving clinical outcomes and survival rates.
This technology is heavily under penetrated in India we have <200 PET-CTs in India, mostly
concentrated in metro cities. India needs more than 1,000 machines spread across the country
- The global WHO standard is 1 PET-CT Scanner per 500,000 people.
PET-CT- A History
While the CT scan was invented in the 1972 and the first Positron Emission Tomography (PET)
Scanner was developed in 1974, more than 25 years passed before Davis Townsend and Ronald
Nutt built and installed the first system at the University of Pittsburgh in 1998.
The first commercial systems were made available in 2001, in which year the PET-CT scan was
recognized by the TIME magazine on its cover as perhaps the most important medical invention
over the previous decade.
In India, the first PET-CT was installed at the Radiation Medicine Centre of BARC in Mumbai.
What is PET-CT?
PET-CT is a fusion imaging technique in which a PET scanner and a CT scanner work together
to acquire images of the human body, which are subsequently put together to give a more
informed view of the state of the body to the doctors.
In one of the rare real-life situations where the whole is considerably more than the sum of its
parts, the functional imaging obtained from the PET, which depicts the spatial distribution of
Metabolic or biochemical activity in the body can be more precisely aligned or correlated with
anatomic imaging obtained by CT scanning.
PET-CT has revolutionized medical diagnosis in many fields, and has become the diagnostic
imaging modality of choice for procedures in oncology, surgical planning, radiation therapy
and cancer staging.
What is FDG?
While PET-CTs are almost miraculous in terms of what they can achieve, there is a significant
obstacle to their widespread use. Production and transport of radiopharmaceuticals used for
PET imaging is complicated, and extremely expensive.
The key radiotracer used for PET-CT scans is FDG (Fluoro DeoxyGlucose). It is a molecule of
glucose in which one of the oxygen atoms has been replaced with a radioactive Fluorine-18
(18F) atom. As this glucose is absorbed and metabolized by the body, the distribution of the
glucose usage identifies cancers, which are effectively abnormal, uncontrolled growths consuming
huge amounts of energy in the form of glucose.
The key challenge with FDG is the extremely short halflife of 18F - approximately 2 hours. In
practice, it means that every two hours of travel time between the cyclotron (which produces
the FDG) to the PET-CT scanner doubles the costs of FDG - which are the single largest variable
cost in any PET-CT business.
How does PET-CT help the Patients?
When detected early, localized cancers can be managed and treated. They can be surgically
excised, and the patients can be regularly monitored.
By diagnosing cancers early, PET-CT helps the doctors in not only improve survivability, but it
also allows them to cheaply and efficiently monitor the impact of the treatment. For a disease,
whose treatment is effectively injecting high doses of chemicals whose speed of killing the
cancer cells is only very slightly faster than the speed at which it kills the human body, this is critical.
Non-invasive, cheap and quick monitoring using PETCT scans helps save the patients from overtreatment
and the debilitating effects of chemotherapy which are capable of significantly reducing quality of life.
Even after a successful treatment, cancers often return, and when they do, they are even Once again,
early detection is the key to successful treatment. Regular monitoring through planned PETCT scans
allows the doctors to efficiently monitor the recurrence of the disease.
Economics of PET-CT Business
While the typical PET-CT Scanner costs anywhere between INR 7 to 10 Crores, the Cyclotron,
which produced the radiotracers without which the PET-CT cannot function costs more than
INR 40 Crores.
This creates a huge entry barrier in what is an otherwise simple business.
Most of the costs, other than FDG in a PET-CT scan business are fixed, and do not scale up
significantly with the number of scans - which means that volumes are the single most critical
factor determining the viability of a PET-CT business.
In a typical set-up, a PET-CT breaks even at - 10 scans per day, while it makes good returns at 15
scans per day. However, given the high costs of FDG, most service providers are pricing PETCT
scans quite high, trading volumes for margins that only serves to reduce the accessibility of this
lifesaving technology for those who need it the most.
The key then, is to also own the cyclotron, which allows one to control the costs of FDG,
and smart network development that optimizes costs of real estate, logistics and manpower to
create an efficient hub and spoke model.
However, it is sad to see that most PETCT scan services are priced very high, and seem to
be either ignoring, or unaware of the volume benefits in this space.
The Cost Angle, and how Nueclear is tackling it
In India, 80% of healthcare spending is private, effectively meaning that pricing is critical to
the ability of a patient to afford a treatment or diagnostic modality.
For a disease like cancer, for which treatment costs can exceed INR 4-5 lakhs, the oncologist
is often forced to treat the cancer aggressively, forgoing the information given by the scan
because the additional financial burden of the PET-CT scans, which are typically priced in
India at INR 15,000 to INR 20,000. The high prices effectively make PET-CT Scans unaffordable
for a very large strata of cancer patients. Nueclear Healthcare Limited (NHL), was created
to challenge this status quo.
Nueclear has made a conscious decision to control every part of the value chain, right from
the production of the FDG to owning the centres.
This allows NHL to offer tests at prices as low as INR 9999-a discount of almost 50% to the
market. NHL uses state of the art machines, employs some of the most qualified doctors in
this field in India and provides unparalleled accuracy, affordability and accessibility to patients.
Nueclear is building a pan-Indian network of Cyclotrons and PET-CT centres. In the next 3-5
years, Nueclear will build a network of - 80 PET-CT machines and 4 cyclotrons serving the
length and breadth of India.
The wider acceptance of PET-CT scans in India will be driven by the availability of qualified
Nuclear Medicine Doctors and better air connectivity linking cyclotrons with PET-CT machines.
Airlines, AERB and the aviation regulator also need to work together to give priority handling
to FDG - given its short half life and life-saving potential.
Lastly, there is a conscious need for patients to be educated so that they are not blindly sent
by doctors to specific centres which have referral based financial arrangements with the doctors.
Such rent-seeking behavior only harms them. Patients need to be informed that they have the
right to choose any service provider of their choice, and that they should make this decision
based on their convenience and affordability.
1. What is Nuclear Medicine?
Nuclear Medicine is a clinical speciality where radiopharmaceuticals are administered to
the patients for various diagnostic and therapeutic applications. Radiopharmaceuticals
are radioactive drugs which consist of two components, one which is radioactive and
the other, non-radioactive. The non-radioactive component determines the mode and
organ of localization (specificity of localization in the organ of interest) and the kinetics
of its biodistribution. The radioactive isotope is tagged to the non-radioactive component
and the radiations emitted are used to form an image of its in vivo distribution.
Nuclear Medicine is broadly classified into "Diagnostic Nuclear Medicine" and
"Therapeutic Nuclear Medicine"
2. What is Diagnostic Nuclear Medicine?
Diagnostic Nuclear Medicine involves administration of trace quantities of radiopharmaceuticals
to diagnose functional abnormalities in body tissues. It involves in vivo imaging, in vivo
nonimaging (e.g. Thyroid Uptake studies, GFR estimation by Plasma sampling) and in vitro
laboratory procedures (e.g. Radioimmuno assays.
The in vivo imaging is broadly divided into Planar Imaging, Single Photon Emission Computed
Tomography (SPECT) and Positron Emission Tomography (PET).
The most commonly used radioisotope for Planar and SPECT imaging is Technetium-99m Tc),
having a physical half-life of 6 hours. The "Momc radionuclide generators are the typical
routine inhouse source of intc availability in a nuclear medicine department. These generators
have a useful life of around 7-15 days and needs to be periodically replaced.
The most commonly used radioisotope for PET imaging is Fluorine-18 (''F). The "F labeled
radiopharmaceuticals are produced in a Medical
Cyclotron facility and are supplied to PET centers. The short half-life of 110 minutes often
does not permit its transportation to distant PET facilities.
The radiopharmaceuticals in nuclear medicine are available in variety of forms viz. solution,
colloidal solution, capsules or aerosols. Depending on its form, they are either administered
intravenously, intracavitatory, orally or through inhalation.
The gamma radiations emitted by the radiopharmaceuticals are detected by specialized
detectors (scintillation, detectors) which convert the incident radiation into light energy.
This light energy is converted into electric signals and is processed further using sophisticated
reconstruction algorithms to generate an image of the biodistribution of the radiopharmaceutical.
3. What is Therapeutic Nuclear Medicine?
Therapeutic Nuclear Medicine involves administration of radiopharmaceuticals for curative
le.g. -Sodium iodide for treatment of hyper-functioning thyroid gland in Graves' disease,
differentiated thyroid cancer) or palliative (e.g. 153Sm-EDTMP for bone pain palliation) applications.
4. How is Nuclear Medicine different from Radiology?
Nuclear Medicine differs from Radiology in the following ways:
(a) Nuclear Medicine involves internal administration of radiopharmaceuticals to the
patients (radiation source is internal) while Radiology involves use of external source of radiation
(b) In Nuclear Medicine, radiations emitted from the radiopharmaceutical inside the
body is used for imaging. In Radiological investigations like X-ray and Computed Tomography
(CT) scan, radiations produced from a X-ray generating device are directed towards the patients
body and radiation transmitted through the body is used for obtaining an image. Difference in
the absorption of X-rays by various tissues is the basis of imaging in these investigations.
Ultrasonography (USG) and Magnetic Resonance Imaging (MRI) do not involve use of radiation.
(c) Nuclear Medicine is unique as it provides functional information of organs or tissues in the body
unlike structural information obtained from radiological investigations like X-ray, CT scan and conventional
MRI scan. Since, the biochemical/functional changes precede morphological changes in the evolution of
disease process, Nuclear Medicine imaging modalities can provide information on metabolic changes at
cellular level and are capable of detecting diseases much earlier than CT and MRI scans.
5. What is Molecular Imaging?
Molecular imaging is a discipline which enables the visualization, characterization and quantitation
of biological processes taking place at cellular level in living organism without affecting them. The
Nuclear Medicine procedures like SPECT and PET imaging, functional MRI and Optical imaging are
examples of Molecular Imaging.
6. What is PET imaging?
PET scan is a functional diagnostic imaging modality which involves administration of positron
radiation emitting radiopharmaceutical, to map the various in vivo biological processes. It provides
clinician with 3-dimensional images and information about how organs/tissues inside the body are
functioning at cellular and molecular level.
7. What is PET-CT fusion imaging?
When a CT scan is performed along with a PET scan as a part of the same diagnostic work up,
it is termed as PET-CT fusion imaging. It uniquely combines the functional information provided
by the PET scan with the anatomical information obtained from the CT scan. Fusion imaging with
a CT scan thus, helps to localize the functional abnormality and also characterize the lesion.
This increases the sensitivity, specificity and overall diagnostic accuracy when as compared to
PET and CT alone.
8. What information does a PET-CT scan provide?
PET-CT has emerged as an important complimentary modality that is advancing our understanding
of the underlying cause of disease and improving disease detection and management. It provides
information that may not be possible to obtain from other imaging techniques or possibly would
require use of more invasive procedures such as biopsy or surgery.
PET-CT fusion imaging helps
1. Diagnose disease in its early stages,often before the patient becomes symptomatic, especially
when other Diagnostic tests are likely to give negative results.
2. Determine the extent and severity of the disease.
3. Individualize therapy based on the unique biological properties of the disease.
4. Evaluate the effectiveness of a treatment regimen.
5. Modify treatment plans in response to altered biological behaviour of the tissue.
6. Assess disease progression.
7. Identify recurrence of disease and further disease management.
9. Which radiotracers are used for PET imaging?
Positron radiation emitting radioisotope based radiopharmaceuticals are used for PET imaging.
Positron per se are not useful for imaging as they will be absorbed within the body. However, the
positrons emitted travel a short distance before losing its kinetic energy. It then annihilates with
an electron to emit 2 photons of 511 keV each which travel in opposite directions. These annihilation
photons (and not positrons) are detected by the PET scanner and the light signals generated are
processed by computers to provide 3-dimensional images of the tracer distribution in the body.
The most widely used PET tracers in India are
F -Fluorodeoxyglucose (F-FDG) & FSodium Fluoride (F-NaF).
Almost 90% of PET-CT studies are performed using F-FDG. F-FDG (also called as "Molecule of
the Century") is a glucose analog group at C-2 position is substituted by F. It is taken up by the
cells via Glucose Transporter (GLUT) receptors and is subsequently phosphorylated by the
Hexokinase enzyme to Fluorodeoxyglucose-6-phosphate. However, it can't be further
metabolized to deoxy
fructose-6-phosphate as this step involves rearrangement of the carbonyl group from C-1 to C-2
position in the ring and thus gets trapped in the cells. This 'metabolic trapping of "F-FDG forms
the basis of "F-FDG PET imaging.
F Sodium Fluoride (F-NaF) is used for imaging of skeletal system. It localizes in the bones by
binding to the hydroxyl group of the Hydroxyapatite. It has higher sensitivity and diagnostic
accuracy than the conventionally used Tc-MDP Bone scan.
10. Is PET-CT scan an O.P.D. procedure?
Yes! PET-CT scan is an O.P.D. procedure.
11. What are the indications for a 18F-FDG PET-CT scan in clinical practice?
F-FDG PET-CT scan has a proven efficacy in various oncological and non- oncological applications.
They are summarized below
(a) Oncological Applications
There are subtle biochemical differences between normal cells and malignant cells. In malignant
cells, there is upregulation of Glucose Transporters (GLUT receptors), over expression of Hexokinase
and absence or very low levels of Glucose-6-Phosphatase. All these factors result in increased
FDG uptake by tumor cells relative to the normal healthy cells. This increased FDG accumulation
by malignant cells, forms the basis of "F-FDG PET-CT scan for oncological applications.
Some of the malignancies in which PET-CT modality is useful in disease management
are described below
A normal FDG PET scan with physiological bio-distribution of F-FDG in brain, Waldeyer's ring,
liver, spleen, myocardium, bowel and urinary bladder.
1. Routine pre-treatment staging of patients with Hodgkin's disease and Non Hodgkin's Lymphoma.
2. Routine restaging after completion of chemotherapy and after radiotherapy.
3. Interim assessment of treatment response for prognostication.
4. Prognostication prior to bone marrow transplant/autologous stem cell therapy.
(11) Carcinoma Lung
1. Solitary Pulmonary Nodule (SPN): To characterize a solitary pulmonary nodule > 1cm in an
individual with an intermediate risk for carcinoma lung.
2. Staging of Non-Small Cell Lung carcinoma (NSCLC).
3. Treatment response assessment post-chemotherapy and radiation therapy in NSCLC.
4. To assess completeness of Radiofrequency Ablation (RFA) of carcinoma lung or pulmonary metastasis.
5. Restaging of NSCLC.
6. Delineation of gross-tumor volume in patients scheduled for radiation therapy.
>> Detection of extra nodal metastases in stage II & Ill malignant melanoma.
>> Evaluation of extent of recurrent disease
(iv) Head and Neck Cancer:
>>Detection of occult primary tumors in patients presenting with metastatic disease.
(v) Carcinoma Esophagus:
>>Pre-treatment evaluation of stage I-Ill cancer.
>>Restaging after neoadjuvant chemoradiation therapy.
(vi) Colorectal Cancer:
>>Preoperative evaluation of patients with potentially resectable hepatic or other metastases.
>>Determining location of tumors if rising CEA level suggests recurrence.
>> To identify anaplastic transformation of non-enhancing low grade gliomas.
>> To grade gliomas non-invasively and guide biopsy.
>> To differentiate radiation necrosis from disease recurrence.
(viii) Thyroid Cancer
1. Detection of residual or recurrent differentiated thyroid cancer when serum thyroglobulin is
elevated and radioiodine scan is negative.
2. Staging of poorly differentiated/anaplastic thyroid carcinoma.
(ix) Carcinoma Breast
Detection of metastatic or recurrent breast cancer in patients clinically suspected of
metastases or recurrence.
(x) Genitourinary Cancer
1. Initial treatment planning, including determination of nodal status and systemic spread.
2. Detection of residual or recurrent disease.
(xi) Musculoskeletal system
1. Staging and interim response evaluation of PNET/Ewings Sarcoma.
2. To assess treatment response to therapy when pretreatment PET-CT scan shows FDG avid lesions.
3. To assess sarcomatous change in Osteochondroma, grade it non-invasively and direct biopsy.
4. To assess the completeness of RFA in cases of Osteoid Osteoma.
5. To differentiate Plasmacytoma from Multiple Myeloma.
1. To stage the disease.
2. Assessment of treatment response.
3. Restaging the disease.
(xiii) Gastro Intestinal Stromal Tumors (GIST)
Treatment response assessment for targeted therapies.
(b) Non-Oncological Applications
Increased glycolysis in the inflammatory cells forms the basis of "F-FDG PET-CT imaging for various
non-oncological pathologies such as aseptic inflammatory conditions as well as in a wide variety of
infections. The non-oncological applications of FDG PET-CT scan are as follows:
1. Pyrexia of Unknown Origin (PUO)
Three categories that account for the majority of PUO are infections, malignancies and collagen
vascular or autoimmune diseases. Early identification and localization of an infectious or inflammatory
process can be critical for the management of these patients. Because of its high sensitivity in
detecting malignant lesions, infections like Tuberculosis, as well as various inflammatory processes,
FDG-PET has the potential to play a central role in the management of patients with PUO.
In cases of temporal lobe epilepsy, increased tracer uptake is noted on the ""Tc-ECD ictal study.
"F-FDG PET-CT interictal scan is performed to increase the specificity of diagnosis.
In its early stages, the identification and differential diagnosis of dementia is especially challenging,
because of the difficulty in distinguishing it from the mild cognitive decline associated with normal
aging, The specific patterns of altered metabolism are suggestive of the cause of dementia. FDG PET-CT
may be the ideal test for selecting appropriate patients for treatment when the disease process is at
the molecular level and before structural alterations have taken place.
To evaluate the extent of disease in diagnosed cases of sarcoidosis and assessing treatment response.
12. What are the indications for a F-NaF Bone Scan in clinical practice?
Recently, F-Sodium Fluoride (NaF) PET-CT scan has gained popularity as an alternative to the conventionally
used TC-MDP Bone scans due to following advantages:
1. NaF PET-CT has higher sensitivity and specificity in distinguishing benign from malignant
lesions as compared to MDP Bone scan.
2. It provides sharper images with higher resolution than conventional, planar bone scan & SPECT.
3. The Fluoride bone scan requires 90 minutes for its completion while the MDP bone scan requires 3-4 hours.
4. Low dose CT associated with PET-CT study increases its specificity and thus obviates the need of
an additional diagnostic CT or MRI scan.
The indications of Naf bone scan are as follows
1. Evaluation of skeletal metastases in a case of Carcinoma prostate,
2. Evaluation for skeletal metastases in stage III & IV Carcinoma breast and symptomatic
cases of Stage 1 &ll.
3. Evaluation of case of Osteogenic Sarcoma.
4. Assessment of treatment response in metabolic bone diseases.
5. Evaluate a case of Osteoid Osteoma prior to and post-RFA for assessment for completion of ablation.
6. Evaluation of low back ache. Prior to radioisotopic bone pain palliation therapy.
13. What are the typical instructions a patient needs to follow for a 18F-FDG PET-CT scan?
1. The patient should strictly fast for atleast 6 hours. Increase in the blood sugar levels after
a meal may competitively inhibit the uptake of FDG in the lesions and thus decrease the diagnostic
sensitivity and overall accuracy of the modality. Also, it causes endogenous release of insulin
which results in increased FDG uptake in skeletal muscles. This altered biodistribution of FDG
makes the study suboptimal for qualitative and quantitative assessment. The patient may,
however, be permitted to drink plain water.
2. The patient should not undertake any intense and strenuous physical activity or exercise for
24 hours before the scan as it results in increased uptake in the skeletal muscles (.e. altered biodistribution).
3. The patient should carry all the relevant medical records, reports, film and/or CD of X-rays,
CT, MRI, PET-CT or any other investigation done till date on the day of the study.
4. An adult attendant should accompany the patient at the time of the scan. The patient should
not be accompanied by children and pregnant women.
1. The patient should wear loose and comfortable clothing on the day of the scan. The patient
should not wear any metallic objects, jewellery or valuables.
2. For nursing and pregnant patients
If a patient is nursing, pregnant or thinks that she may be pregnant, she should inform the
staff at the time of appointment.
3. For diabetic patients only
in addition to the earlier instructions
The patient should not take any anti-diabetic medicines (tablets/insulin injections)
on the day of the scan.
The patient should have a good glycemic control. A fasting blood sugar of < 150 mg/dl
14. What are the typical instructions a patient needs to follow for a F-NaF Bone scan?
1. The patient need not be fasting at the time of the study.
2. Diabetic patients can have breakfast and their anti-diabetic medicines. High blood sugar does
not interfere with the results of the scan.
3. Rest of the instructions to be followed are same as those for "F-FDG PET-CT scan
(mentioned in the previous section).
15. How is a PET-CT scan routinely performed?
The patient is injected with the radiopharmaceutical and asked to stay in a separate room
for approximately 45-75 minutes. This mandatory waiting period is required for the radiotracer
to localize in the target tissues. The patients are advised to restrict physical movements and
avoid talking to others while present in the room. During this resting period, unless recommended
by the staff, no attendants or relatives would be permitted to stay with the patients.
1. The patient may be given oral contrast to drink. This will help to obtain more informative
images of the abdomen. Just before starting the scan, the patient would be asked to pass urine,
2. The patient is then subjected to scanning and during the scanning, it is expected to remain
still for 15-20 minutes.
3. After the completion of scanning, the PET-CT scan is reviewed for quality and adequacy of the study,
4. The PET-CT scan is finally examined by an experienced Nuclear Medicine Physician and
findings are reported.
16. Are PET-CT procedures safe and cost-effective?
Yes! The PET-CT procedures are safe, painless, non-invasive and cost-effective.
17. Does one experience any discomfort during the PET-CT procedure?
PET-CT scan procedures are rarely associated with any significant discomfort or side effects.
18. Is the amount of radiation received from a PETCT scan very high?
A PET-CT scan have two components: a PET scan and a CT scan, which are done in tandem. For
a PET scan, radiopharmaceutical is injected in small (tracer) quantities. It is excreted from the
body through urine. The unexcreted, radiopharmaceutical decays with a short half-lite (110, minutes).
Thus, the amount of radiation exposure received by the patient is very low.
The estimated effective dose from a typical PET scan is 7 milliSievert (mSv). It is equivalent
to the radiation dose receive from natural environment in 3 years. The effective dose from
CT has a very wide range (8-30 mSv) depending on the type of the test, the region of the
body scanned and the purpose of the test.
19. Does PET-CT scan cause any allergic reactions?
The radiopharmaceuticals used for PET scan are absolutely safe and have no reported
The CT scan done as a part of PET-CT procedure may be performed with or without contrast
enhancement. These contrast agents are known to cause allergic reactions in few patients
as seen with any
other contrast enhanced CT procedure. The routinely used non-ionic contrast media are safe.
However, in very few cases some side effects may be noticed like;
Minor Reactions: Itching, rashes, chills, nausea and vomiting. They are self-limiting
and require no treatment.
Moderate reactions: They include dyspnea, tachycardia, generalized erythema, mild hypotension.
The chance of such reactions is 1 in 1,000 i.e 0.1%.
Severe Reactions: They occur rarely and include convulsion, cardiopulmonary arrest, profound
hypotension and arrhythmias. One in 1,00,000 studies (i.e. 0.001%) may lead to death.
20. Can a breast-feeding mother undergo a PET-CT scan?
Yes! However, it is recommended that the patient does not breast-feed her baby for 6-8 hours
after the scan has been performed as small amounts of the administered radiopharmaceutical
might be excreted in breast milk. It is advisable to collect expressed breast milk before the
radiotracer injection, so that it can be used to feed the baby.
21. Are there any restrictions on patient's social behavior after a PET-CT scan?
Generally, there are no restrictions on patient's social behavior after a PET-CT scan.
The patients may resume their routine activities immediately after the scan is over. However,
it is advisable to avoid prolonged contact with infants, small children and pregnant women
for at least 6 hrs after the scan.
22. How long does it take to get a PET-CT scan report?
The PET-CT scan results are usually available within 2 days.
23. What is the future of PET-CT imaging?
With wide availability of PET-CT scans, metabolic biopsy is likely to be adopted on a
large scale. Such biopsies are likely to yield reliable and better diagnostic results.
With the development of new specific radiotracers and targeted therapies, improvement
in resolution of the imaging systems and fusion imaging with MRI, the existing list of
applications of PET scan in clinical practice is likely to increase.