Specialties

The field of Nuclear Medicine is a rapidly evolving specialty which is based on evaluation of function of living tissue. The Department of Nuclear Medicine in Hinduja Hospital is dedicated in providing advanced diagnostic and treatment solutions to many diseases, as well as many fundamental insights into the complex workings of the human body. The scans can help detect physiological changes that often occur prior to morphological changes leading to early diagnosis of disease.

What is Nuclear Medicine and how it works

Nuclear Medicine works by examining the regional chemistry of any living tissue using radioactive agents and is used to diagnose and treat patients. Very small amounts of unsealed (open) radioactive sources are used internally through a vein or mouth or inhalation. It is separate from Radiation therapy where large amounts of radiation from sealed radioactive sources are used externally. Nuclear Medicine imaging identifies the functional changes caused by diseases.

Nuclear Medicine, Radiology and Medical Imaging

Essentially, it falls under the broad umbrella of Medical Imaging in most modern health care institutions. Morphologic or structural modalities of diagnostic imaging (the branch of Radiology) such as X-ray, Magnetic Resonance Imaging (MRI), Transmission Computed tomography (CT scan) or Ultrasonography are complemented by Nuclear medicine procedures like SPECT (Single Photon Emission Computed Tomography) or PET (Positron Emission Tomography). Anatomical abnormalities are best diagnosed by morphologic modality’s high-resolution examinations whereas Nuclear Medicine studies are optimally utilized when the information sought is primarily physiological and biochemical in nature. As a result, most of the current equipments are hybrid, capable of looking at both the structure and function through one examination (SPECT-CT or PET-CT). The diagnostic accuracy and the confidence of the reporting physician are enhanced by hybrid imaging.

The strength of Nuclear Medicine: tissue characterization

Nuclear Medicine evaluates several biological processes like metabolism, receptor expression, apoptosis and other molecular changes happening at a cellular level. Indeed, Nuclear Medicine is more often referred to as “molecular imaging” in recent times. Biological molecules which are specific to certain cells or tumors can be radiolabelled and injected to the patient to monitor specific cell functions or tumor behavior. This makes “tissue characterization” possible, which is a big step towards fulfilling the concept of “personalized medicine”, where no two patients with the same disease are treated in an identical way. For example, the current method of assessing tumor response to therapy, by measuring tumor volume or glucose metabolism, is useful but clearly inadequate and in the near future we will not only be looking at these parameters but also be able to measure other indices of tumor behaviour like cell proliferation, receptor expression or internal hypoxia and may therefore treat patients in an individually tailored and a truly personalized manner.

Over-regulation of the specialty

Yet, the specialty continues to remain over regulated, which is the biggest threat to its expansion. Mass radiation hysteria following the atomic holocaust during the second world war was craftily utilized by a group of professionals (health physicists) in the United States in the 1950’s who scared the senators to a great extent to pass a vast body of legislations that were too harsh and disproportionate to the risk involved in most diagnostic nuclear medicine procedures. The dose of radiation involved in atomic bomb survivors were extrapolated to the miniscule amount of radiation involved in diagnostic procedures to predict detriment (adverse effect), a method which is not unquestionable. Indeed, there is accumulating data that a small dose of radiation has no effect on human body and probably has some beneficial effect (radiation hormesis), stimulating the activation of repair mechanisms that protect against disease that are not activated in absence of ionizing radiation.

Is radiation harmful and how to measure it

Radiation exposure is an intangible concept, not measurable by commonly perceived yardsticks. An average nuclear medicine procedure (4-5 mSv) gives a third of the amount of exposure to individuals of what an inhabitant of the coast of Kerala is exposed to in one calendar year (14 mSv) through natural radiation from the Monazite sands and we are not aware of any increased incidence of cancer in them. This piece of information can probably put radiation exposure in some sort of a comprehensible perspective. When one out of every three individuals is likely to have cancer in their lifetime, a small increase (if at all) in the risk (incidence of 1 in 2000 or 1 in 5000) does not really make a difference.

Other legislative constraints

There has been a significant impediment to radiopharmaceutical (the radioactive chemical injected to trace a biological process) development because of heavy legislations. The process of registration of new radiopharmaceuticals, which are administered once or twice, in quantities less than a milligram with extremely rare side effects, is the same as for drugs that are given daily in doses of several hundreds of milligrams. It is not a fair bargain for the specialty!

Both diagnosis and therapy

Although most of the current nuclear medicine practice is diagnostic, there are many therapeutic uses of unsealed radioactivity. Therapy is performed with a different group of radioisotopes which can potentially cause cellular kill and damage. Because of their potential to cause damage, radionuclide therapy has got to be targeted at the organ of interest with a greater precision. The following sections will outline the uses of SPECT/Gamma imaging, PET and radionuclide therapy.

Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to diagnose or treat a variety of diseases, including many types of cancers, heart disease and other abnormalities within the body.

Nuclear medicine or radionuclide imaging procedures are noninvasive and are usually painless tests that help physicians diagnose medical conditions. Depending on the type of nuclear medicine examination, the radio-tracer is either injected into a vein, swallowed or inhaled as a gas and eventually accumulates in the organ being examined, where it gives off energy in the form of gamma rays. This energy is detected by a device called a gamma camera or a PET (positron emission tomography) scanner. These devices work together with a computer to measure the amount of radio-tracer absorbed by the body and to produce special pictures offering details on both the structure and function of organs and tissues.

The following section describes imaging with a gamma camera capable of performing SPECT (Single photon emission computed tomography). However imaging performed with a gamma camera is often two dimensional, called planar imaging. Tomography is not mandatory in all procedures except the brain and the heart.

Cardiovascular Nuclear Medicine

The first use of radioactivity in humans was made in the 1930’s to measure cardiovascular transit time. The first clinical success was achieved in measuring the cardiac pump function in the 70’s. Cardiovascular procedures are only next to bone scanning in numbers in an average nuclear medicine department. The following applications are now routinely available.

Nuclear imaging procedures in Cardiology

• Ventricular performance (pump function of the heart) is measured by a technique called equilibrium radionuclide ventriculography after labeling red blood cells with Technetium-99m which is the workhorse radionuclide in gamma imaging. Imaging can be done at stress or rest and this method is the most reproducible of all techniques used to assess cardiac pump function.
• Myocardial perfusion reserve is an established measure of the significance of narrowing of coronary arteries. It is now established that opening up of any blocked artery does not necessarily improve outcome except in the setting of an acute coronary syndrome (heart attack). Regional myocardial perfusion (blood flow at the tissue level), which is measured by the Potassium analogue, Thallium 201 and various Technetium labeled agents, is a commonly requested procedure where blood flow is measured both after stress and rest. This is called myocardial perfusion imaging (MPI)
• Myocardial metabolism is conventionally measured with PET techniques although SPECT agents like radio-iodinated fatty acids (BMIPP) are increasingly appreciated as markers of tissue viability.
• Evaluation of autonomic innervations is now possible with SPECT techniques using 123-Iodine MIBG. The availability of the beta receptors in the heart is an accurate indicator of prognosis in patients with poor left ventricular function. Two patients with the same pump function but different degrees of sympathetic innervations have different outcomes.
• Acute myocardial necrosis can be imaged using appropriate SPECT agents like Technetium 99m-glucarate and has potential clinical utility in disease processes like coronary artery disease, myocarditis, transplant rejection and drug induced cardio-toxicity.
• Myocardial apoptosis (programmed cell death) can now be imaged noninvasively using Tc99m-Annexin which has potential applications in patients with heart failure and transplant rejection.

Clinical applications of cardiac nuclear medicine

• Diagnosis of coronary artery disease: CAD can be established or excluded with a high sensitivity and specificity using MPI. It is the most appropriate diagnostic test in patients with an intermediate probability of CAD. For patients with a high clinical probability an invasive procedure is more cost effective.
• Prognostic assessment of CAD: Quantitative assessment of regional perfusion is the most accurate indicator of future risk of coronary events. A normal scan identifies a low risk population regardless of the presence of angiographic disease. And indeed, as demonstrated by the landmark COURAGE trial, such patients with no or limited ischemia do not need intervention and do equally well with optimal medical therapy.
  Conversely, patients showing high risk features on a perfusion scan need intervention to reduce future coronary risk. In an ideal world, perfusion scan should act as the gatekeeper of angiographic procedures in patients with non acute chest pain.
• Acute ischemic syndromes: Nuclear techniques can be used in the emergency department to evaluate patients with chest pain. Separation into high or low risk categories depending on the regional perfusion at rest can reduce unnecessary hospital admissions.
  Risk stratification of patients after a non Q wave myocardial infarction using MPI is useful in the assessment of the need for invasive procedures. Patients with no ischemia are best treated conservatively without any adverse outcome.
• Preoperative risk assessment: MPI is the most accurate marker of peri-operative cardiac risk in patients undergoing non-cardiac surgery who demonstrate high or intermediate high risk as judged by other clinical variables.
• Tissue viability: Patients with poor LV function due to CAD often benefit from surgical revascularization (CABG) if it can be demonstrated that the poorly pumping areas have viable tissue left in them that are ischemic in MPI. Dead and scarred areas do not demonstrate benefit. SPECT techniques using delayed Thallium redistribution or Nitrate augmented Technetium labeled agents are helpful in this context although metabolic imaging with FDG PET is more accurate.

Nuclear Medicine in Oncology

Although the coming of age of FDG PET has significantly reduced the contribution of conventional gamma/SPECT imaging in clinical oncology, there are many areas where it continues to contribute to the care of patients with cancer. The role of PET is separately outlined in the next section.

Cancer staging

Determining if a cancer has spread is crucial for treatment planning. Patients with metastatic disease are not candidates for surgery. Locally contained cancer can be considered for surgical resection, if feasible. SPECT/Gamma imaging contributes significantly in this area.

• MDP Bone scanning: It is probably the most commonly performed procedure in conventional nuclear imaging. Metastasis to bone provokes local reaction in the form of new bone formation which is picked up by the bone scanning agent 99Tc-methylenediphosphonate. Metastases from many cancers like prostate, lung, breast, lung, esophagus or primary bone tumors can be detected by an MDP bone scan, earlier than radiographic changes.
• 99mTc-SestaMIBI: Although MIBI was originally approved as a myocardial perfusion agent; its tumor seeking behavior has been particularly exploited in assessing breast masses of uncertain significance to guide the clinician for the need of a biopsy. A breast mass that does not take up MIBI is unlikely to be cancerous.
  A two phase MIBI scan is an excellent imaging method to identify benign parathyroid tumors called adenomas. They are often symptomatic and need surgical removal. Surgeons are particularly helped if the adenomas can be localized before surgery so that the incision in the neck is small and precise
• 67 Gallium: The use of 67-Gallium imaging in staging and assessing treatment response in lymphoma is now essentially of historical interest as FDG PET has completely replaced Gallium imaging. In the absence of PET, gallium is of good clinical benefit for assessing tumors involving the chest. Gallium can differentiate hepatoma from regenerating nodules in cirrhosis. Gallium avid tumors are melanoma, seminoma and rhabdomyosarcoma. Because of its bowel excretion, it cannot be used to assess abdominal malignancies
• 201 Thallium: Like MIBI, thallium was originally a heart seeking radionuclide, whose predilection for viable cells found a new use in the assessment of viable tumors too. Localization of remnant viable tumor after therapy, particularly in brain tumor or osteosarcoma, is the main clinical use of thallium in oncology. Brain tumor in patients with HIV that is both thallium and gallium avid is likely to be lymphoma and a purely thallium avid lesion is likely to be Kaposi’s sarcoma.
• 123 or 131-Iodine-MIBG: MIBG is probably the second most useful SPECT/Gamma agent after MDP in cancer. Localization of neuro-endocrine tumors that take up nor-epinephrine is possible with either 123 or 131-Iodine labeled MIBG. These include pheochromocytoma, paraganglioma, neuroblastoma, etc. MIBG also allows treating the same tumors with the therapeutic 131-Iodine isotope. The PET agent 68-Gallium-DOTATATE has largely replaced diagnostic MIBG imaging because of its superior sensitivity and specificity due to a vastly improved image quality and accurate localization with CT
• 111-Indium-Octreotide:Receptor based nuclear medicine techniques include low molecular weight peptides which binds to receptors on the tumor cells. Tumors that express somatostatin receptors have been successfully imaged with labeled Octreotide (a somatostatin analogue). They include carcinoid tumors, pancreatic tumors, medullary thyroid carcinoma, etc. However, like MIBG, this SPECT agent has also been largely replaced by 68 Gallium-DOTATATE for its superior image quality.
• Radiolabelled monoclonal antibodies: Tumors express antigens against which antibodies can be raised and tagged with radiolabels, thus allowing visualization of tumor or its metastases and also therapy with suitable radionuclides. However, the earlier enthusiasm with immunoscintigraphy in cancer dampened primarily because of the increased availability of FDG PET and also because of the limited sensitivity and specificity of monoclonal SPECT. Colorectal (Oncoscint), prostate (Prostascint) and lung cancer have been successfully staged by various 111-Indium or 99m-Tc labeled monoclonal antibodies in the past.
  However, with the increasing availability of PET and the inability of FDG to address a number of different cancers, there has been a renewed interest in monoclonal antibody imaging with PET radionuclides like 89-Zirconium or 124-Iodine
• Sentinel node localization with lymphoscintigraphy: The modern concept of sentinel node was reported in 1977 for penile carcinoma. In the context of a tumor that is known to spread by lymphatic channels, sentinel node is the first draining lymph node (from an organ) which can be imaged by infiltrating some radioactive colloid material around the tumor area. If the first draining lymph node can be mapped and shown to be free of disease, there is no need to perform a full regional removal of lymph nodes to avoid the morbidity and cost associated with such complex surgery.
  Accurate identification of individual lymphatic patterns in cancer patients is becoming a norm and blind surgical resection of nodes based on anatomical guidelines, an exception. Sentinel node imaging has been validated and found particularly useful in melanoma and breast cancer. The recently published NSAPB 32 study comparing Sentinel lymph node biopsy (SLNB) plus axillary lymph node dissection (ALND) with SLNB alone found no difference in the rates of recurrence (8 year survival of 91.8% vs. 90.3% in more than 5600 patients)

Evaluation of treatment response

There are many therapeutic options in cancer management and often it is important to monitor both the response of the tumor and the response of other healthy organs to different forms of cancer therapy which are potentially toxic to any dividing cell.

Serial bone scanning in patients with metastatic carcinoma of the prostate can be very helpful to monitor the response to hormone therapy. The timing of the bone scan is also crucial as successful therapy can make the appearance of the scan a little worse in the first 3 months due to normal healing response of the affected bone, described in the literature as a “flare phenomenon”

Anthracyclin antibiotics which are important cancer chemotherapeutic drugs have toxic effects on the heart. Patients are serially followed up with radionuclide ventriculography for monitoring their cardiac function. Appropriate changes are made in the chemotherapy dosage depending on their effect on the heart.

Many anticancer drugs have a toxic effect on the kidneys and patients who are treated with such drugs are often monitored with serial renography or estimation of their GFR by nuclear techniques.

Neuclear Medicine in Neurology and Psychiatry

Before the advent of CT scanning, the role of nuclear medicine in neurology was extensive. Any pathology that disrupted the blood brain barrier had a potential to be imaged by scintigraphy in that era. However, the use of nuclear medicine is now limited to functional imaging studies only.

The radiopharmaceuticals 99mTc-HMPAO and 99mTc-ECD are the two commonly used cerebral perfusion agents. They are lipophilic and extracted on the first pass through the brain after an IV injection and reflect perfusion. Their uptake is highest in the cortex and the sub cortical grey matter. On imaging, the central areas of reduced uptake are primarily white matter and not the ventricles. The principal areas of application of SPECT are as follows.

• Cerebrovascular disease: Measurement of cerebral blood flow at various stages of stroke may provide important information that is not provided by other structural modalities of imaging.
  Cerebral infarction: The parameters that correlate well with a patient’s prognosis are the extent of blood flow reduction and the presence of early reperfusion, both provided by SPECT.
  Transient ischemic attack: In a very early stage of TIA, structural imaging may be negative. Early SPECT scan can reveal a perfusion defect in brain, confirming the diagnosis. Patients having TIA are at risk of completed stroke in the future and it is important that we can predict them. SPECT can be performed at baseline and after a vasodilator stress with Diamox that can identify the vasodilator reserve in an individual with TIA. Less the reserve, higher the chance of a stroke in the future.
  Subarachnoid hemorrhage: Neurologic deficits that develop in SAH due to vasospasm can be diagnosed with a SPECT scan and appropriate measures can be taken to reduce the spasm on time.
• Diagnosis of brain death: Radiopharmaceuticals that are used to assess blood flow to the brain (HMPAO or ECD) can also be used to confirm brain death by demonstrating the lack of uptake in brain. It is difficult to interpret such scans in prolonged vegetative states and in children.
• Assessment of brain trauma: Derangement in blood flow and metabolism in brain can happen after trauma in the absence of structural abnormalities on CT or MRI. Functional impairment on nuclear scans is often more extensive and correlates better with neuropsychiatric ratings in the long term. Objective evidence of impaired blood flow in areas of brain after head trauma can have medico legal implications.
• Focal epilepsy: Focal epilepsy that is not controlled by medications can be cured by surgery. For this, preoperative localization of the epileptic focus in the brain is essential. At rest, there is reduced flow or metabolism in the focus. During seizure, the same focus shows a dramatic increase in flow and metabolism. By a timely injection of ECD or HMPAO, epileptic foci can be identified with a high degree of positive predictive value.
• Dementia: The diagnosis of dementia is still based on clinical findings but there are significant limitations of clinical indices. Cerebral blood flow and metabolism often show distinctive patterns that are suggestive of certain types of dementia. Blood flow reduction in bilateral temporal and parietal lobes of the brain is suggestive of Alzheimer’s disease whereas reduced flow in bilateral frontal lobes is suggestive of Pick’s disease. Scattered areas of reduced flow along vascular territories suggest multi-infarct dementia
• Movement disorders: Parkinson’s disease is a common movement disorder resulting in tremor and sluggish movement. Loss of dopamine producing neurons in the striatum of the brain is responsible for this and these neurons (Dopamine transporters) can be imaged by 123-Iodine-FPCIT or 99mTc-TRODAT. Dopamine Transporter Imaging can differentiate essential tremor and Alzheimer’s dementia (no Dopamine loss) from Parkinsonian tremor and Lewy body dementia respectively.
• Brain tumors: The role of SPECT in brain tumors has been discussed in the Oncology section.
• Cerebrospinal fluid imaging: Common indications for CSF imaging are for evaluation of a suspected CSF leak or for differentiating normal pressure hydrocephalus from other causes of hydrocephalus. 99m Tc-DTPA is injected in the subarachnoid space in the lumbar spine (spinal tap) and the ascent and flow of the tracer to the brain is monitored and imaged for 24-48 hours.
• Drug discovery and evaluation: Until recently, drug action at the level of neuro-receptors in brain had to be deduced from in-vitro studies on animal or human post-mortem brain tissue and from effects on animal behaviors thought to reflect symptoms and signs of mental illness in man. With SPECT (and PET), pharmacokinetic behavior of drugs can be detailed and pharmaco-dynamic relationships defined and these techniques are indispensable for drug discovery and evaluation in neuropsychiatry.

What is Positron Emission Tomography (PET) and why PET

Positron emission tomography, also called PET imaging or a PET scan, is a type of nuclear medicine imaging. Conventional nuclear medicine imaging done with a gamma camera is often referred to as SPECT (Single photon emission computed tomography). PET is performed with a different set of isotopes which emit positrons (that subsequently produces high energy gamma rays for imaging) and can only be imaged with a dedicated PET camera. Because of the nature of PET isotopes, more physiological molecules can be used as tracers for imaging biological processes. Because of the inherent higher resolution of the technique and its ability to quantify the biological process, PET is considered to be the future of nuclear medicine.

PET-CT imaging

The current form of a PET scanner is a dedicated PET-CT machine in which the same gantry unit houses both the PET scanner and the CT scanner. PET-CT is a unique tool that combines the highly sensitive nature of isotope imaging with the localizing power (high specificity) of CT anatomical imaging, creating fusion images, showing both function and anatomy.

Applications of PET-CT

Although PET has a distinct role to play in the understanding and diagnosis of physiology and pathology of many organs, most current applications are useful in Oncology, Cardiology, Neurology, Infection and inflammation and of these; majority of the work is being done in Oncology.

PET-CT in Oncology

It was first observed in the 1930s that accelerated glucose metabolism is present in tumors. The most widely used PET radiopharmaceutical is 18Fluorine-FDG. FDG is a glucose analogue, which once injected, is transported to the cells which have an increased glucose demand. Unlike the glucose molecule, FDG remains trapped inside a cell long enough to allow optimum time for imaging. Since cancer cells have higher glucose requirement than normal cells, they take up FDG in a higher concentration than the surrounding normal cells.

On account of the similarity of the FDG molecule to a glucose molecule, it is possible to quantify the metabolic rate. The most common quantification technique in clinical PET is SUV (standardised uptake value). SUVs are often used to differentiate malignant from benign lesions, or cancer from only inflammation or infection (a lower SUV value could indicate a benign etiology).

PET has proven to be a useful tool at several stages of cancer management. They include

• Staging (initial evaluation of disease extent)
• Treatment response to chemotherapy and/or radiotherapy.
• Prognosis and tumor recurrence.
• Distinguishing benign from malignant tumors.
• Identifying residual disease.

Different cancers have different requirements in terms of PET-CT imaging, the details of which are beyond the scope of this information portal. For example, PET -CT scan is useful in the staging of lung cancer, whereas its main role in colorectal cancer is assessment of suspected recurrence and restaging.

One of the most important advantages of PET imaging is that it allows a whole-body scan with a single radioactive dose. It is not rare to find a second cancer or an unexpected site of the disease. However, FDG is not tumor-specific and is taken up by any metabolically active cell. This property can be exploited by using FDG in various conditions in which the metabolic activity of a cell is increased, e.g. malignancy, inflammation and infection. So it is important that a carefully designed clinical history is obtained before FDG injection.

The predominant indications of FDG-PET in Oncology are listed. As more data have become available, the importance of PET imaging has increased for diagnosis, staging and restaging for various cancer types.

Other Radiopharmaceuticals for PET-CT in Oncology

It is now apparent that 18-Fluorine is the future PET isotope for years to come for its favorable physical and biological properties. Shorter lived isotopes like 11Carbon or 13Nitrogen or 15Oxygen need a cyclotron onsite (production site) and therefore have little prospects outside University hospitals. The current commercial PET radiopharmaceutical research is centered on 18F and a couple of generator based PET isotopes like 68Gallium and 82Rubidium.

• 68 Gallium-DOTATOC is the second most commonly used radiopharmaceutical in PET imaging in Oncology. Excellent images are obtained in patients with suspected tumors of neuroendocrine origin that express Somatostatin receptors. Now, there are opportunities to treat similar patients with peptides labeled with a therapeutic isotope like 90 Yittrium or 177 Lutetium.
• 18 F-Choline and 18 F-Ethylcholine are compounds whose clinical utility is currently being explored in prostate carcinoma, for exclusion of lymph node involvement in primary staging and identification of tumor in patients who show a biochemical recurrence with an increasing PSA level.
• 18 F-Thymidine has been evaluated as a marker for cellular proliferation, with mixed results. A tumor which has been treated successfully with radiotherapy can continue to show glucose metabolism because of the resultant inflammation and Thymidine can distinguish proliferative (cancer) cells from inflammatory (non cancer cells)
• 18 F-Ethyltyrosine is an amino acid and unlike FDG, amino acids do not accumulate in inflammatory processes and could thus potentially provide a more specific tumor label. Unfortunately, they are less sensitive than FDG for tumor staging. It is likely that they will continue to play a role in brain tumor imaging because, unlike FDG, they do not accumulate in normal brain tissue.

PET-CT in Cardiology

Myocardial Perfusion
Regional myocardial blood flow assessment is performed with both SPECT and PET but the latter allows absolute quantification of blood flow, thus enhancing the sensitivity of the technique. Of all the different PET isotopes that can be used, the generator based 82 Rubidium is an attractive option as it is available in the department for an extended period after purchase and has gained importance during the recent periods of shortage of Technetium which is the workhorse of SPECT imaging.

Myocardial Viability
PET is one of the most accurate tests for assessing myocardial viability. PET does this by measuring myocardial glucose metabolism using FDG. Patients with poor left ventricular function due to coronary artery disease need this test to predict the effect of revascularization, prior to surgery.

Normal myocardium can obtain energy from either fatty acids or from glucose. When a section of the myocardium becomes ischemic, it switches over to glucose metabolism as its sole source of energy. Because anaerobic glucose metabolism is inefficient, the amount of glucose that is consumed can be almost as high as normal myocardium. However, if that section of the myocardium is scarred and no longer viable, then it will not take up FDG at all.

When an area of poor perfusion continues to take up FDG, then it is viable (called a perfusion, metabolism mismatch). However, when an area of hypo-perfusion has a corresponding area of hypo-metabolism, that section of the myocardium is no longer viable. Non viable segments are unlikely to benefit from revascularization.

PET-CT in inflammation and infection

The marked accumulation of FDG in white blood cells (activated macrophages) makes FDG PET useful in imaging patients with inflammatory disease. Localization of inflammatory foci in soft-tissue or bone structures and the anatomical information provided by CT are complimentary. The disease entities involving inflammation and infection, where FDG PET is useful, are as follows:

• Fever of unknown origin: infectious foci or sterile inflammatory processes (eg, vasculitis)
• Widespread soft-tissue infections
• Suspected chronic osteomyelitis
• Infected orthopedic implants

PET-CT in Neurology

Although, most of the current clinical applications of PET relate to oncology, it was in the field of neurology and psychiatry, PET was first used for both clinical and research purposes. In neurology, PET provides information for assessing various neurological diseases such as Parkinson's disease and other movement disorders, Alzheimer's disease and other dementia, epilepsy and stroke.

• Movement disorders: 18 F-DOPA PET can provide an image of the function and integrity of dopamine producing cells in the brain which are responsible for Parkinson’s disease. It can help differentiate patients with Parkinsonian tremor from those with ordinary tremor.
• Dementia: FDG PET has been used extensively to study dementia and it may be an effective tool for early diagnosis and differentiation of various types of dementia. Alzheimer’s disease (AD) patients exhibit characteristic reduction in glucose metabolism in the temporal and parietal lobes of the brain. 18F-Florbetapir is a recently approved tracer, which can measure the beta-amyloid burden of the brain and help not only establishing the diagnosis of Alzheimer’s disease but also predict it in asymptomatic patients.
• Epilepsy: Complex partial seizures in a significant proportion of patients remain uncontrolled despite optimal medical therapy. The main clinical uses of PET in epilepsy are localization of epileptogenic foci in potential surgical candidates with partial seizures and corroborating findings from other investigational modalities such as electroencephalography (EEG) and MRI
• Stroke: Following a stroke, PET can not only identify a “core” region of irreversibly damaged tissue but also the “penumbra” of reduced perfusion but normal oxygen consumption, an area that may yet be saved by reperfusion therapy. However, these studies need cyclotron produced isotopes and are not routinely available.
• Neuro-pharmacology and drug development: PET receptor ligand studies have generated a wealth of knowledge about disease pathogenesis and potential therapeutic targets for novel pharmaceutical agents. It is an essential tool for development of drugs.

It is rather curious that Nuclear medicine gained public recognition as a potential specialty following a therapeutic application. The time was very unfavorable for anything that sounded “nuclear” (1946) when an article was published in the Journal of the American Medical Association by Sam Seidlin. He described a successful treatment of a patient with metastatic thyroid cancer using radioiodine. This is considered by many historians as the most important article ever published in nuclear medicine.

In nuclear medicine therapy, the radiation treatment dose is administered internally (e.g. intravenous or oral routes) rather from an external radiation source. Radionuclide therapy can be used to treat conditions such as hyperthyroidism, thyroid cancer, blood disorders, bone pain due to cancer and many types of tumors. Most nuclear medicine therapies can be performed as outpatient procedures since there are few side effects from the treatment and the radiation exposure to the general public can be kept within a safe limit.

1. Benign and malignant thyroid disease with 131 Radioiodine

In earlier times, I-131 was only used in the therapy of thyroid cancer; over a period of time its use extended to include imaging of the thyroid gland, thyroid function quantification and hyperthyroidism therapy.

Radio active iodine (131-Iodine) is used for treating overactive thyroid disorders. The conventional drug therapy for this condition has side effects, needs prolonged treatment (around 18 months) and even after that, there is a 30-40% chance of recurrence. Radioiodine can be used as a single therapy to cure this disorder with a significantly higher patient comfort and compliance.

Malignant thyroid tumors are cured by a combination of surgery and radioactive iodine and there is an excellent prognosis of patients with differentiated thyroid cancer who are treated this way. Iodine therapy for thyroid cancer requires a patient to be admitted to the hospital and be discharged only when the radiation levels are below permissible limits.

2. Overactive bone marrow with 32 Phosphorus

Radioactive phosphorus is used for the treatment of overactive bone marrow when other forms of therapies fail or are not tolerated by the patient. There are several forms of myelo-proliferative disorders where certain blood cells may increase in number causing problems. A common example is increased number of platelets (thrombocytosis) causing thrombosis.

3. Bone pain due to cancer with 89 Strontium and 153 Samarium

Intractable bone pain due to widespread metastases can be successfully treated using these isotopes. Patients, who do not respond to conventional analgesics and have documented bone metastases, benefit from this therapy. It is important to note that this form of therapy is only palliative and not curative.

4. Radiosynovectomy with 90 Yttrium

Radioactive Yttrium injected into a joint space in a colloidal form can be very useful in reducing inflammation and pain in big joints like knee. The synovial membrane of the joint is the source of inflammation and pain and radiation induced damage of the inflamed membrane is equivalent to a surgical removal (without a knife). Smaller joints of hands and feet can also be treated using appropriate radionuclides.

5. Treatment of cancers with 131-Iodine, 177 Lutetium and 90 Yttrium labeled compounds

The radiopharmaceuticals used in nuclear medicine therapy emit ionizing radiation that travels only a short distance (beta rays as against gamma rays, which are emitted by diagnostic isotopes), thereby minimizing unwanted side effects and damage to noninvolved organs or nearby structures. If the isotope can be carried by a biological agent (antibodies or peptides) that selectively goes to the target areas, it is possible to fulfill the concept of “magic bullets” or “smart bombs” in cancer therapy whereby only the cancer cells are killed and normal cells spared. The enthusiasm in the pursuit of this form of therapy has not met with proportionate success but yet this remains one of the most potential areas for future research.

• 131-Iodine-MIBG (metaiodobenzylguanidine) has been successfully used treating many types of neuroendocrine tumors including pheochromocytoma or neuroblastoma in children.
• 90-Yttrium-ibritumomab (Zevalin) and 131-Iodine-tositumomab (Bexxar) are approved for treating refractory lymphoma. This method of treatment using radio-labeled antibodies against antigens expressed by tumors is called Radio-immunotherapy.
• Yttrium-90-glass spheres (TheraSphere) are approved for treating hepatocellular carcinoma through an artery directly feeding the tumor. All currently used treatments for inoperable liver cancer that reduce the symptoms of this disease require hospitalization, and usually cause side effects that reduce the quality of life for patients. Therasphere therapy does not require hospitalization and has fewer side effects than most conventional therapies.
• 177 Lutetium or 90 Yttrium-DOTATOC are radio-labeled peptides that are approved and widely available for treating patients with metastatic tumors that express somatostatin receptors. Following the success of the diagnostic agent 68 Gallium-DOTATOC in imaging these tumors, the field of Peptide Receptor Radionuclide Therapy has been expanding rapidly. There are many tumors that express somatostatin receptors.
• 213 Bismuth and 211 Astatine labeled peptide therapy. Targeted alpha-particles offer specific tumor cell kill with less collateral damage to surrounding normal tissues than beta-emitters. Alpha emitters like 213 Bismuth or 211 Astatine have been tagged with various peptides which bind to tumor receptors. What continues to obstruct widespread acceptance of alpha-emitter-labeled peptides are primarily the supply of these isotopes and concerns about potential kidney toxicity. This form of therapy is still not available on a commercial basis.

In summary, therefore, nuclear medicine continues have its unique role in treating benign and malignant diseases. There is ongoing research with more powerful isotopes in targeted cancer therapy.