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 non-imaging
(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-CT Scan).
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
(e.g. ** -Sodium lodide for treatment of hyperfunctioning thyroid gland in Graves disease,
differentiated thyroid cancer) or palliative (e.g.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 PET-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, PET-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-CT Scan, functional MRI and Optical imaging are examples
of Molecular Imaging.
6. What is PET imaging?
PET-CT 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 PETCT 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;
- Diagnose disease in its early stages, often before the patient becomes symptomatic, especially when
other Diagnostic Test are likely to give negative results.
- Determine the extent and severity of the disease
- Individualize therapy based on the unique biological properties of the disease.
- Evaluate the effectiveness of a treatment regimen.
- Modify treatment plans in response to altered biological behaviour of the tissue.
Assess disease progression.
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
(FFDG) & "F-Sodium Fluoride (F-NaF).
F-Fluorodeoxyglucose (F-FDG)
Almost 90% of PET-CT studies are performed using F-FDG. F-FDG (also called as "Molecule of the Century")
is a glucose analog in which the hydroxyl 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-6phosphate. 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 18F-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 F-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 phosphate dehydrogenase (G6PD). 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
(1) Lymphoma:
- Routine pre-treatment staging of patients with Hodgkin's disease and Non Hodgkin's Lymphoma.
- Routine restaging after completion of chemotherapy and after radio therapy.
- Interim assessment of treatment response for prognostication.
- Prognostication prior to bone marrow transplant/Autologous stem cell therapy .
(ii) Carcinoma Lung
- Solitary Pulmonary Nodule (SPN): To characterize a solitary pulmonary nodule > 1cm in an individual with an
intermediate risk for Carcinoma lung.
- Staging of Non-Small Cell Lung carcinoma (NSCLC).
- Treatment response assessment post-chemotherapy and radiation therapy in NSCLC.
- To assess completeness of Radiofrequency Ablation (RFA) of carcinoma lung or pulmonary metastasis.
- Restaging of NSCLC.
- Delineation of gross-tumor volume in patients scheduled for radiation therapy.
(iii) Melanoma
- Detection of extra nodal metastases in stage II & III malignant melanoma.
- Evaluation of extent of recurrent disease.
(iv) Head and Neck Cancer
- Detection of occult primary tumors in patients presenting with metastatic disease.
- Initial staging, including detection of cervical lymph node metastases when the neck nodes are not
palpable and detection of distant metastases in patients with locally advanced disease.
- Detection of residual or recurrent disease.
(v) Carcinoma Esophagus
- Pre-treatment evaluation of stage l-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.
(vii) Brain
- 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
- Detection of residual or recurrent differentiated thyroid cancer when serum thyroglobulin is
elevated and radioiodine scan is negative.
- 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
- Initial treatment planning, including determination of nodal status and systemic spread.
- Detection of residual or recurrent disease.
(xi) Musculoskeletal system
- Staging and interim response evaluation of PNET/Ewings Sarcoma,
- To assess treatment response to therapy when pre-treatment PET-CT scan shows FDG avid lesions.
- To assess sarcomatous change in Osteochondroma, grade it non invasively and direct biopsy.
- To assess the completeness of RFA in cases of Osteoid Osteoma,
- To differentiate Plasmacytoma from Multiple Myeloma,
(xii) Neuroblastoma
- To stage the disease.
- Assessment of treatment response.
- 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
- 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.
- Epilepsy
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.
- Dementia
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.
- Sarcoidosis
To evaluate the extent of disease in diagnosed cases of sarcoidosis and assessing treatment response.
- Vasculitis involving major vessels
To evaluate the extent of disease and monitor effectiveness of therapy.
- Cardiology
To assess viability in dysfunctional myocardial segments.
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
- NaF PET-CT has higher sensitivity and specificity in distinguishing benign from malignant lesions as compared
to MDP Bone scan.
- It provides sharper images with higher resolution than conventional planar bone scan & SPECT.
- The Fluoride bone scan requires 90 minutes for its completion while the MDP bone scan requires 3-4 hours.
- 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
- Evaluation of skeletal metastases in a case of Carcinoma prostate.
- Evaluation for skeletal metastases in stage III & IV Carcinoma breast and symptomatic cases of Stage 1 & ll.
- Evaluation of case of Osteogenic Sarcoma.
- Assessment of treatment response in metabolic bone diseases.
- Evaluate a case of Osteoid Osteoma prior to and post-RFA for assessment for completion of ablation.
- 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 F-FDG PET-CT scan?
- 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.
- 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 i.e. altered biodistribution).
- 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.
- An adult attendant should accompany the patient at the time of the scan. The patient should not
be accompanied by children and pregnant women.
- 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.
- 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.
- 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 is desirable.
14. What are the typical instructions a patient needs to follow for a "F-NaF Bone scan?
- The patient need not be fasting at the time of the study.
- Diabetic patients can have breakfast and their anti-diabetic medicines. High blood sugar does not
interfere with the results of the scan.
- 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.
- 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.
- The patient is then subjected to scanning and during the scanning is expected to
remain still for 15-20 minutes.
- After the completion of scanning, the PET-CT scan is reviewed for quality and adequacy of the study.
- The PET-CT scan is finally examined by an experienced Nuclear Medicine Physician and findings 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 PET-CT scan very high?
A PET-CT scan has 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-life (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 allergic reactions.
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, generalised eryth-ema, 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. 0.01%) 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 patients' 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.
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
