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 image its invivo distribution.
Nuclear Medicine is broadly classified into “Diagnostic Nuclear Medicine” and “Therapeutic Nuclear Medicine”.
What is Diagnostic Nuclear Medicine?
Diagnostic Nuclear Medicine involves administration of trace quantities of radiopharmaceuticals to diagnose functional abnormalities in body tissues. It involves invivo imaging, invivo non-imaging (e.g. Thyroid Uptake studies, GFR estimation by Plasma sampling) and invitro laboratory procedures (e.g. Radioimmuno assays.
The invivo 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 (99mTc), having a physical half-life of 6 hours. The 99Mo-99mTc radionuclide generators are the typical routine in-house laboratory source of 99mTc 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 (18F). The 18F 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.
What is Therapeutic Nuclear Medicine?
Therapeutic nuclear medicine involves administration of radiopharmaceuticals for curative (e.g.131I-Sodium Iodide for treatment of hyperfunctioning thyroid gland in Graves’ disease, differentiated thyroid cancer) or palliative (e.g. 153mSm-EDTMP for bone pain palliation) applications.
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 are 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 an organ 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.
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 perturbing them. The Nuclear Medicine procedures like SPECT and PET imaging, functional MRI and Optical imaging are examples of Molecular Imaging.
What is PET imaging?
PET scan is a functional diagnostic imaging modality which involves administration of positron radiation emitting radiopharmaceutical, to map the various invivo 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.
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 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 compared to PET and CT alone.
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;
• Diagnose disease in its early stages, often before the patient becomes symptomatic, especially when other diagnostic tests are likely to give negative results.
• Assessment of the extent and severity of the disease.
• Individualise therapy based on the unique biologic 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 help manage ongoing care.
Which radiotracers are used for PET imaging?
‘Positron radiation emitting’ radioisotope based radiopharmaceuticals are used for PET imaging. Positron perse 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 available PET tracers in India are 18F –Fluorodeoxyglucose (18F-FDG) & 18F-Sodium Fluoride (18F-NaF).
18F-Fluorodeoxyglucose (18F-FDG): Almost 90% of PET-CT studies are performed using 18F-FDG. 18F-FDG (also called as “Molecule of the Century”) is a glucose analog in which the hydroxyl group at C-2 position is substituted by 18F. 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 cannot 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 18F-FDG forms the basis of 18F-FDG PET-CT scan.
18F Sodium Fluoride (18F-NaF): It is used for imaging the skeletal system. It is localized in bones by binding to the hydroxyl group of the Hydroxyapatite. It has higher sensitivity and diagnostic accuracy than the conven-tionally used 99mTc-MDP Bone scan.
Is PET-CT scan an O.P.D. procedure?
Yes! PET-CT scan is an O.P.D. procedure.
What are the indications of 18F-FDG PET-CT scan in clinical practice?
18F-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 up regulation 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 18F-FDG PET-CT scan for oncological applications.
Some of the malignancies in which PET-CT modality is useful are described below:
• Routine pre-treatment staging of patients with Hodgkin’s disease and Non Hodgkin’s Lymphoma.
• Routine restaging after completion of chemotherapy and after radiotherapy.
• 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) 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.
(iv) Carcinoma Esophagus:
• Staging of stage I-III cancer.
• Restaging after neoadjuvant chemoradiation therapy.
(v) 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.
(vii) 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.
(viii) Carcinoma Breast:
(ix) Genitourinary cancer:
• Initial treatment planning, including determination of nodal status and systemic spread.
• Detection of residual or recurrent disease.
(x) Musculoskeletal system:
• Staging and interim response evaluation of PNET / Ewings Sarcoma.
• To assess treatment response to therapy when pre-treatment PET-CT 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.
• To stage the disease.
• Assessment of treatment response.
• Restaging the disease.
(b) Non-Oncological Applications
Increased glycolysis in the inflammatory cells forms the basis of 18F – FDG PET-CT imaging for various non-oncological pathologies such as aseptic inflammatory processes 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.
In cases of temporal lobe epilepsy, increased tracer uptake is noted on the 99mTc-ECD ictal study. 18F-FDG 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 may be the ideal test for selecting the 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.
• Vasculitis involving major vessels:
To evaluate the extent of disease and monitor effectiveness of therapy.
To assess viability in dysfunctional myocardial segments.
What are the indications of 18F-NaF Bone Scan in clinical practice?
Recently, 18F- Sodium Fluoride (NaF) PET-CT scan has gained popularity as an alternative to the conventionally used 99mTc-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 and 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 and IV carcinoma breast and symptomatic cases of Stage I and II.
- 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.
What are the typical instructions a patient needs to follow for a 18F-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 (a glucose analog) 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 tracer 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 < 150mg/dl is desirable.
What are the typical instructions a patient needs to follow for a 18F-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 of 18F –FDG PET-CT scan (mentioned in the previous section).
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 60-90 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. It may be repeated if required.
• The PET-CT scan is finally examined by an experienced Nuclear Medicine Physician and findings are reported.
Are PET-CT procedures safe and cost-effective?
Yes! The PET-CT procedures are safe, painless, non-invasive and cost-effective.
Does one experience any discomfort during the PET-CT procedure?
PET-CT scan procedures are rarely associated with any significant discomfort or side effects.
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.
Sr. No. Procedure Effective Dose(mSv) 1 18F FDG PET scan 7 2 99mTc Bone Scan 4.4 3 Whole body CT scan 8-30 4 CT head 2 5 CT chest 8 6 CT abdomen 10 7 CT pelvis 10 8 Coronary Angiography 5-15 9 Mammography 0.13 10 X-Ray chest 0.04 11 X-Ray Abdomen 0.7
The estimated effective dose from a typical PET scan is 8 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.
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 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. 0.01%) may lead to death.
Can a breastfeeding mother undergo a PET-CT scan?
Yes! However, it is recommended that the patient does not breastfeed 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.
Are there any restrictions on patients’ 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.
How long does it take to get a PET-CT scan report?
The PET-CT scan results are usually available within 2 days.
What is the future of PET-CT imaging?
The accessibility of PET-CT scans has led to the widespread availability of metabolic scan which 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.