The diagnosis of brain cancer can be one of the most devastating times in a person's life because of the swift nature of the disease and its grim prognosis. Once diagnosed, doctors prepare an aggressive strategy to combat the cancer which included brain surgery that carves away a portion of the cancerous tumor, chemotherapy, and radiation treatment. This aggressive strategy would not be possible without the advancements and commercialization of new molecular imaging modalities of positron emission tomography, single photon emission computed tomography, and magnetic resonance spectroscopy. These modalities may provide oncologists with a better understanding of the growth, location, size, and grade of the tumors that result from brain cancer. Molecular imaging has lead to better diagnosis and treatment which is proved by the survival of patients with brain tumors improving 16% since 1971 (McKinney, 2004, p. ii15)
In the review of related literature "New Methods for Direct Delivery of Chemotherapy" (2006) stated that every year, roughly 14,000 people are incapacitated with brain cancer. The consensus in a study of patients diagnosed with brain cancer and their caregivers conducted in 2007 was that brain cancer is "unique in that the organ affected is traditionally viewed as the seat of an individual's literal sense of identity (Bernstein, Kimmelman, et. al., 2007, p.2)." According to research previously published by Michael Blake and Mannudeep Kalra, the prospect for patients with primary brain tumors continues to be very low with the outlook of survival past five years being less than 31%t. It has been suggested that the health care community conduct periodic screening for brain cancer but, Targeted Molecular Imaging in Oncology (2001) suggested that indiscriminate radiographic screening procedures have not improved the prognosis for cancer sufferers nor been deemed necessary from a cost standpoint. Research conducted by Fang, Gregorio, et. al., asserted that the cause of brain cancer is still a mystery. Although there is no known cause of brain cancer "Potential Residential Exposure to Toxics Release Inventory Chemicals during Pregnancy and Childhood Brain Cancer" (2006) declared that radiation exposure to children is the leading environmental hazard of childhood brain cancer. The American Cancer Society (2006) stated that there is no blood test or other screening exam currently available to detect brain tumors or cancer in the brain.
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In "Brain Tumours: Incidence, Survival, and Aetiology" (2004) Dr. Patricia McKinney acknowledged that "improved diagnostic imaging, following introduction of radioisotope imaging, computed tomography, and magnetic resonance imaging in the 1970s and 1980, have resulted in higher detection rates and better differential diagnosis of brain tumor which might have previously been diagnosed as stroke or metastatic tumors." Comments in New Trends in Cancer for the 21 Century suggested that the increased notion of customized treatment and therapy for patients has resulted in a rise of the need to understand pathologies at the molecular level. Conclusions arrived from the "Cost of Temozolomide Therapy and Global Care for Recurrent Malignant Gliomas followed until Death" stated that the cost of treating brain cancer is made up of several components including initial diagnosis, therapy, and support care. In conclusion, this review addresses the continued improvement of the diagnosis and treatment of brain cancer by the implementation of molecular imaging.
Cancer arises when cells in the body begin to grow out of control. Rather than die in a timely fashion these cells continue to develop more abnormal cells. The cause of this abnormality is a mutation of a cell's DNA. In a normal cell the body would repair the cell's DNA; in cancer cells the body is not capable of repairing the cell (American Cancer Society, 2008, p. 1). There are two types of brain cancer, primary and mestastic. Primary brain cancer begins in the brain and mestastic brain cancer is initiated somewhere else in the body and spreads to the brain. The focus of this research paper will be molecular imaging and its use in the diagnosing and treatment of primary brain cancer. Brain Cancer results the development and growth of tumors. A tumor is an anomalous mass of tissue that servers know natural purpose and grows at a rate that is not consistent with normal body tissue (Kim, Yang, 2001, p. 8). The World Health Organization has established a four level categorization system that gives tumors certain "grades" from one to four. In this system a Grade I, a benign tumor, is a tumor that grows slowly in a non-aggressive manner or does not invade surrounding tissue. A Grade IV is a malignant tumor which is a cancerous tumor that grows rapidly and invades all surrounding tissue. (Blake, Kalra, 2008, p. 67). A benign tumor can still be deadly depending on its inclination to become malignant, its ability to penetrate the surround tissue, and its location (McKinney, 2004, p. ii12). The most malignant tumors, astrocytomas and glioblastoma multiforme, which are Grades III to IV tumors, have a 2% to 30% survival rate in the first five year (Blake, Kalra, 2008, p. 67). Tumors are self-governing victimizing mass that are destructive (Kim, Yang, 2001, p. 8).
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Brain cancer can manifest itself in many symptoms. Most symptoms occur because of pressure inside the skull. Pressure within the skull caused by the growth of tumors initiates headaches, nausea, vomiting, or blurred vision. In about 50% percent of patients, headaches are the initial symptom that leads to the diagnosis of brain cancer. In general less than 1% of all headaches are caused by brain cancer. In extreme cases patients with brain cancer may develop abnormal sleepiness an even coma. The majority of people who come to the emergency room and later are diagnosed with brain cancer enter the ER for a new onset of epileptic seizures. Roughly 10% of new onset seizures are caused by brain tumors. These tumors agitate the brain and cause these epileptic seizures. Tumors often damage nerves causing loss of function, weakness of a body part, loss of hearing, abnormal sensation, or even numbness (American Cancer Society, 2008, p. 10-11).
Fang, Gregorio, et. al., stated in their research "the cause of brain cancer are largely unknown, and while research have identified several genetic abnormalities that relate to specific malignant disease, only about 5% of the primary brain cancers are known to be associated with hereditary factors." Although this perception is disputed in "Brain Cancer Mortality in the United States, 1986 to 1999: A Geographic Analysis" which suggested that the scientific community by and large has come to acknowledge that changes in a person's genetic structure (which could be hereditary or initiated) by ecologic aspects cause brain cancer. Ionizing radiation is the only verified environmental hazard that causes brain cancer. Other environmental factors such as exposure to vinyl chloride and petroleum products have been associated with increased risks in some studies (American Cancer Society, 2008, p. 8). Various chemicals such as N-nitroso compounds, phenols, pesticides, polycyclic aromatic hydrocarbons, or organic solvents have been shown to increase the possibility of brain cancer, and some researchers have linked childhood brain tumors with agriculture-related exposures (Fang, Gregorio, et. al., 2004, p. 183). Low dose radiation treatment of tinea capitis, skin disorders, and ringworm of the scalp in children escalated the possibility of brain cancer for children, luckily those treatments have been long discontinued (McKinney, 2004, p. ii15). Radiation-induced brain tumors are frequent in adults who as children received radiation treatment for leukemia, with the cancer appearing 10-15 years after treatment (American Cancer Society, 2008, p. 8). In a study conducted by Choi, Kaye, et. al., they observed an increased rate of the diagnosis of brain cancer before their tenth birthday for children who were born to mothers living within a one mile radius of a facility emitting carcinogens.
In the past there have been many myths that the public have associated with the cause of brain cancer. A variety of chemicals and products have received attention as possible links to brain cancer. Hair dyes and hair sprays were once associated as environmental risk factors for brain tumors in some early epidemiological studies but the observations remain unsubstantiated (McKinney, 2004, p. ii16). Aspartame, a sugar substitute, was implied as risk factors, but research concluded that there was no connection (American Cancer Society, 2008, p. 8). According to an investigation done in "Brain Tumours: Incidence, Survival, and Aetiology" numerous studies have associated some types of tumors to dental x-rays although there seems to be no connection between diagnostic x-rays and brain cancer. Choi stated that "diagnostic x-rays with their usual low dose and short exposure periods were not enough to result in brain cancer." With the increase of mobile phone usage there has been a growing consensus that the radiofrequency associated with these mobile devices might increase the risk of brain cancer. Current epidemiological and biological studies show no relationship between mobile usage and the risk of brain tumors. However with the significant rise in the ownership and duration of usage of handheld mobile phones it will be essential to resume analysis of cell phones as a lifestyle incurred etiology, allowing several decades for the development of brain tumors and studies to evaluate the relationship (McKinney, 2004, p. ii15). Brain cancer does not have a "lifestyle-associated etiology" therefore prevention is not yet achievable (Felipo, Llombart-Bosch, et. al., 2006, p. 286).
In 2006 the morbidity of brain and other nervous system tumors was approximately 19,000 new cases diagnosed in the United States. The tumors were the cause of death or mortality in 12,820 patients in that same year (Blake, Kalra, 2008, p. 67). In the United Kingdom Dr. Patricia McKinney estimated 4,400 people are newly diagnosed with brain tumors each year compared to over 40,000 women with breast cancer and roughly 25,000 men with prostate cancer. In England and Whales from 1986 to 1990 only thirty percent of adults diagnosed with malignant brain tumors survived the first year and fifteen percent lived pass five years. For patients diagnosed between 1981and 1985 only 8% survived to 10 years. Men are more likely to be diagnosed with brain cancer than women with the ratio of men to women being 1.5 to 1 (McKinney, 2004, p. ii12-ii13). Once diagnosed the rate of death is somewhat higher among men than women and has increased over 20 years. The newly published Atlas of Cancer Mortality in the United States showed an increased rate for brain and other nervous system cancers for white males and females in the northwestern, north central, and southeastern areas, with low rates in the southwest and northwest. White Americans have higher brain cancer mortality rates than African-Americans. Another interesting correlation was established between certain occupation and the rate of recurrence of brain cancer. It was determined that brain cancer is more common among workers in oil refining, rubber manufacturing, and drug manufacturing, as well as among farmers (Fang, Gregorio, et. al., 2004, p. 179-183). The cost of treating brain cancer is a major concern to patients. Treating brain cancer contains several cost factors including the diagnosis, the cost of initial therapy, the cost of follow-up, and the cost of treatment for recurrence and support care. Total cost of care range from 2,900 to a little less than 40,000 dollars per patient. Data showed 75% of the cost was sustained in the original treatment period (Leyvraz, Ostermann, et. al., 2005, p. 190-194).
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Brain tumors are the leading cause of death in children under age fifteen (Felipo, Llombart-Bosch, et. al., 2006, p. 285). For children living in the United States, brain cancer is the second most common cancer (Fang, Gregorio, et. al., 2004, p.179). According to Imaging in Oncology (2008) primary brain tumor is the most common solid tumor in children. Patients age nineteen or younger have a five year survival rate of 65%. Patients aged forty-four or younger have a five year survival of less than 59%. In the elderly, prognosis is particularly poor with a five year survival of less than 6.5% in patients aged 65 and older (Blake, Kalra, 2008, p. 67). Despite its lethal nature since 1971 survival for children with brain tumors has improved by 16% in England and Wales. In studies that looked between the year 1986 and 1990 the prognosis in children is better than adults with an overall possibility of surviving to five years of 59% in England and Wales compared to 72% in the US (McKinney, 2004, p. ii15).
Brain cancer is habitually deadly although it is very rare (Bernstein, Kimmelman, et. al., 2007, p.2). Despite surgery and radiotherapy, the prognoses of patients diagnosed with brain cancer remain meager, with an average survival of 9 to 24 months (Leyvraz, Ostermann, et. al., 2005, p.189). The swift nature and limited time of life expectance for patients diagnosed with brain cancer require patients and their love ones to face tough decision about how to proceed as far as treatment comparing quality of life to quantity of life. In research conducted by Bernstein and Kimmelman a conclusion was reached that quality of life was more significant than the continuation of life in the opinions of patients and there family. One patient interviewed stated that the logic behind their thoughts was that "the brain is the big center of everything" and that he was concerned about losing the things that made him who he is as an individual. The diagnosis of brain cancer affects every single aspect of life for the patients and their caregivers (Bernstein, Kimmelman, et. al., 2007, p. 4-5).
Once brain cancer is suspected the next step is a definite diagnosis. To get a 100% diagnosis a biopsy is performed. A biopsy is an examination in which a sample of the believed cancerous tissue is removed and examined under a microscope by a pathologist. The pathologist determines if the tumors is benign or malignant. Once diagnosed the first step in most cases is to surgical removal of as much of the tumor as safely possible. Depending on several factors including, location, grade, and size the neurosurgeon may choose to perform a craniotomy to remove as much tumor as possible. The bone is exposed by peeling the scalp back and small holes are drilled in the skull. When tumors are located within the brain a small incision is made into the brain to allow the surgeon to reach the tumor. The surgeon uses MRI, CT, or ultrasound imaging to direct them to the tumor location. The goal of the surgeon is to remove as much tumor as possible without sacrificing critical brain tissue that control essential bodily functions. Before the surgeon cuts away suspected cancerous tissue he or she electrically stimulates the tissue in and around the tumor to see what functions that part of the brain controls. This technique is accredited with allowing the surgeon to decrease the risk of removing vital parts of the brain that could disable the patient. The recovery time in the hospital is usually four to six days although on average full recovery is reached several weeks after surgery. In cases where the tumor is too deep within the brain, located in portions of the brain with important function, the patient is unable to tolerate a major operation, or parts of the brain necessary for life would be destroyed surgery is not an option (American Cancer Society, 2008, p. 14-16).
The next method in fighting brain cancer is radiation therapy. Brain tumors that are not completely cured by surgical means are treated with high-energy radiation to kill the remaining cancer cells. An external radiation beam similar to diagnostic x-rays, but which last longer, is concentrated exactly on the tumor over the course of several weeks. Radiotherapy is a chief therapeutic option for patients with brain tumor. Another method of delivering radiation therapy called interstitial radiotherapy or brachytherapy places radioactive material directly into the tumor. The disadvantage of radiation therapy is that while it kills the tumor it also damages healthy tissue that surround the tumor. A new technique called 3D conformal therapy uses computers and CT scanners to precisely match the radiation beam to the shape of the tumor, allowing treatment with less damage to the surround brain tissue. In some conditions doctors may decide to use stereotactic radiosurgery. In this method while the patient is conscious, a halo is attached to the patient's head and CT or MRI scans are used to measure the location of the tumor with respect to the halo frame. In this treatment several low dose radiation beams are directed from different directions to meet at the tumor. The low dose radiation beams combine together at the tumor to kill the cancerous cells. Gamma Knife, adapted linear accelerators and cyclotrons are all methods of stereotactic radiosurgery (American Cancer Society, 2008, p. 17-18).
Another option for treatment of brain cancer is chemotherapy. These pharmaceuticals are a series of drugs that impede tumor cells from dividing. Anticancer drugs are given intravenously or by mouth which allows them to reach all areas of the body. One of the drawbacks of chemotherapy is that because of the blood-brain barrier some drugs are less likely to reach the brain. This means that a chemotherapeutic agent given by mouth or into vein is less likely to make its way into a brain tumor than in other organs (American Cancer Society, 2008, p. 18). Polymeric-controlled release and convection-enhanced delivery are two methods for local delivery of drugs to brain tumors. These methods attempt to tackle the need for controllable intracranial drug delivery (Piepmeier, Saltzaman, et. al. 2006, p. 149). The most commonly used drugs are temozolomide, BCNU (carmustine), and cisplatin. BCNU is often distributed in a dissolvable chemotherapy wafer called a Gliadel which is placed directly in the tumor. Erlotinib (Tarceva) and gefitinib (Iressa) are growth factor inhibitors used to shrink tumors. Drugs such as dexamethasone (Decadron) are given to reduce the swelling that take place around brain tumors. These drugs help alleviate symptoms such as headaches. These combinations of drugs eliminate cancer cells but they also can harm normal tissue and cause severe side effects. Normal tissue, such as bone marrow, the lining of the mouth and intestine, and hair follicles can be affected by chemotherapy. Consequently a patient may experience hair loss, mouth sores, lowered resistance to infection, easy bruising or bleeding, fatigue, loss of appetite, nausea, and vomiting. Most of these side effects go away after treatment. Chemotherapy drugs can also cause permanent damage to organs and tissue including the heart, kidneys, and nerves (American Cancer Society, 2008, p. 18-19).
Imaging plays an important role in the diagnosis of brain cancer. Early imaging methods were invasive and sometimes dangerous such as cerebral angiography. In this imaging method a special dye is injected into the blood vessels, allowing the doctor to view the blood supply to the tumor (American Cancer Society, 2008, p. 13). These methods were discarded for the high resolution modalities of molecular imagining. Molecular imaging creates noninvasive in vivo studies of physiological and pathophysiological processes at the cellular and molecular level. At this moment in time, molecular imaging may be used for demonstrating a variety of processes including metabolism, apoptosis, cellular trafficking, receptor expression, and gene expression. Molecular imaging can be attained by nuclear medicine techniques, optical imaging as well as magnetic resonance imaging. Nuclear medicine techniques are split into modalities that use positron emitters and those using gamma emitters. New Trends in Cancer for the 21 Century (2006) states that "molecular imaging has become during the last several years an important tool for supporting cancer diagnosis and prognosis. PET and SPECT are the most common molecular imaging techniques although very promising and specific biological molecular agents contrast for CT and MRI are being recently developed" (Felipo, Llombart-Bosch, et. al., 2006, p. 277-285). This research paper will spotlight magnetic resonance spectroscopy and positron emission tomography.
The introduction of magnetic resonance imaging has resulted in increased diagnosis of brain tumors (McKinney, 2004, p. ii13). According to Targeted Molecular Imaging in Oncology (2001) MRI provides exceptional tissue contrast resolution, direct multiplanar imaging, no ionizing radiation, capacity to image blood flow, increased sensitivity to edema, and very low occurrence of reaction to MRI contrast agents. MRI has a 60% to 90% diagnostic accuracy rate depending on the tumor type and grade (Felipo, Llombart-Bosch, et. al., 2006, p. 286). The disadvantages of using MRI can be high cost, poor cortical bone detail and inherent contraindications with ferromagnetic foreign bodies or implants (Kim, Yang, 2001, p. 7).
Magnetic resonance spectroscopy is a type of molecular imaging that involves magnets to provide images and biological information while the patient is conscious and alert. MRS is similar to MRI, except that radio waves interact with different atoms within the tissue and the images highlight features of brain tumors that are not clearly seen by MRI. MRS is used to measure the level of different metabolites in body tissues. The MR signal produces a spectrum of resonances that correspond to different molecular arrangements of the isotopes being "excited." The signature is used to diagnose certain metabolic disorders, especially those affecting the brain (American Cancer Society, 2008, p. 12). Hydrogen Magnetic Resonance Spectroscopy (H MRS) can simultaneously supply numerous molecular images using endogenous metabolites. MRS can construct an average metabolic profile of the chosen tissue area and provide biochemical spatial information. According to New Trends in Cancer for the 21 Century (2006) H MRS is the only noninvasive method that can make available six profiles per "pass" of chemical distribution in a tumor and be used to explore molecular profiles of brain tumors. This is essential in the treatment of brain cancer to establish if the combination of drug, radiation therapy, and chemotherapy are reducing the size of the tumor. After radiation treatment a substantial number of patients grow new lesions at or near the original tumor site. These lesions can be treatment-induced damage, tumor recurrence, or progressive tumor growth. Molecular information through the metabolic spatial distribution provided by MRS images can be used for the diagnosis of radiation induced injury respect to recurrence. In the beginning MRS, in particular H MRS was extensively utilized to expand the diagnosis and prognosis of central nervous system pathologies, specifically brain tumors. However during the last year the MRS applications have been applied to the diagnosis of different very common cancer types such as breast, prostate, and ovarian, among others (Felipo, Llombart-Bosch, et. al., 2006, p. 285-295).
The newest molecular imaging modality to begin to reach mass commercialization use is positron emission tomography. PET is a type of molecular imaging that involves nuclear medicine imaging techniques which produces a three-dimensional image or map of functional processes in the body while the patient awake. PET works when a positron is released it will be neutralized by an electron (annihilated) and two protons will be emitted traveling in opposite directions (180 degrees). It is these two simultaneously emitted photons that are detected by a PET scanner. It is not possible to discriminate between different positron emitters since the energy of the radiation is always 511KeV (Felipo, Llombart-Bosch, et. al., 2006, p. 277-278). In Imaging in Oncology (2008) it is stated that "with PET, molecular and physiological processes involved in the working of healthy or diseased human brains can be studied at a level of anatomic and quantitative detail that was previously impossible." Beforehand the health care community could only understand what went on within the brain from post-mortems or animal studies before PET scanner were instituted. Data obtained from PET studies have a greater level of quantitative reliability than the results that can be obtained with any other imaging modality. PET obtains in vivo regional biomedical and physiologic information about healthy and disease human brain tissue while the patient is at ease, conscious and alert. This ability is the result if four major technological improvements. The first improvement was the ability to create "user friendly" cyclotrons of positrons emitting isotopes. Secondly are the techniques for the rapid production of radiopharmaceuticals required for biochemical and physiologic studies. Third are mathematical models and practical algorithms to obtain decisive information from the data. The final advance was the capacity of PET instrumentation to safely detect the radiopharmaceuticals in a regional and quantitative manner. PET has the potential of making available quantitative images of a variety of physiological and biochemical processes, including blood flow, blood volume, blood-brain barrier permeability, oxygen utilization, glucose utilization, amino acid transports, protein synthesis, cell proliferation and tissue hypoxia (Blake, Kalra, 2008, p. 67-68).
The tracer FDG (2-[18F]-fluoro-2-deoxy-d-glucose) is at this time the most frequently used radiopharmaceutical for imaging brain tumors. This is due to the wide accessibility of this tracer and the relationship between glucose metabolism and malignancy. FDG functions as a trapped tracer that provides a snapshot of glucose utilization at the time of injection. Other tracers labeled with 15O, 11C, and 18F have also been in use for imaging brain tumors. Tracers labeled with 15O include bolus injected H215O or inhaled C15O for examining tumor perfusion. C15O is excellent for surveying tumor blood volume. Tracers labeled 11C, include methionine, leucine and tyrosine are beneficial for research of amino acid transport and protein synthesis in tumors. Tritiated thymidine, when labeled with 11C, is the "gold standard" for analyzes cell proliferation, is an exceptional tracer for studying cell proliferation in brain tumors by PET. 11C may have an advantage over FDG for differentiating recurrent tumors from radiation necrosis. Unfortunately, due to necessities of an on-site cyclotron and radiochemistry facilities and the short physical half-life of 15O (2min) and 11C (20min), tracers labeled with these radionuclides are not practical for routine clinical applications (Blake, Kalra, 2008, p. 70).
In the preliminary diagnosis of brain tumors FDG-PET has been enormously effective in measuring tumor grade, recognizing the most favorable sites for biopsy, an evaluation of prognosis. For FDG-PET studies patients are instructed to have no caloric intake for at least four hours preceding the injection. Following intravenous injection of the tracer the patients rest quietly in a softly lit room for forty-five minutes during the tracer uptake. During this uptake period sight and sound are purposely minimized to prevent cortical activation that could influence image interpretation. Images are obtained in six to eight minutes while the patient is in a recumbent position. Imaging in Oncology (2008) states that "the regional metabolic data provided by FDG-PET in brain tumor patients provides important information about tumor grade, prognosis and recurrence." Glucose is nearly the exclusive energy substrate for brain metabolism. As a result, normal brain tissue has a very high background buildup of FDG, specifically in gray matter structures. The level of FDG utilization in even high grade tumors is similar to normal gray matter structures. This physiological collection of FDG in normal structures reduces the conspicuity of lesions and limits the capability of FDG-PET to detect and differentiate small lesions. Noticeably, image interpretation can be greatly assisted by co-registration with MRI and/or database of FDG uptake in normal brains. The levels of FDG accumulation in a primary brain tumor provide important information in the prognosis of brain cancer. A study referenced by Imaging in Oncology (2008) showed that patients with hypermetabolic tumors (fast growing) had a one year survival rate of 29% compared with patients with hypometabolic tumors (slow growing) whose one year survival rate was 78%. In other studies it was concluded that the prognostic value could be enhanced by serial scans. Post surgical changes, following tumor removal, can show abnormal enhancement on MRI studies. Since post surgical changes do not result in FDG accumulation recurrent tumors can be excluded from these abnormalities that would have previously been diagnosed as a recurrent tumor. Following radiation therapy, radiation is usually linked with reduced FDG accumulation in the treatment area. In a study by Chao it was demonstrated that FDG-PET had a sensitivity of 75% and a specificity of 81% for differentiation of recurrent tumors who underwent stereotic radiosurgery. In patients with brain metastasis, co-registration of PET with MRI increased sensitivity from 65% to 86% (Blake, Kalra, 2008, p. 70-77).
The exceptional metabolic information provided by FDG-PET can be extremely valuable in both the initial diagnosis, post-therapy, re-evaluation of brain tumors. The major advantage of FDG as a PET tracer is it's widely available, the long physical half-life of 18F, compared with other positron emitters, and the association between glucose utilization rate and tumor grade. These factors have important practical, diagnostic, and prognostic implications for the medical and surgical management of patients with brain tumors. The major disadvantages of FDG-PET are inadequate spatial resolution and high background activity in gray matter. Although CT and MRI provide superb anatomic detail, they do not yield metabolic information and are limited value in measuring tumor grade. When FDG-PET are co-registered with CT or MRI data, fusion images of metabolic and anatomic information provides a powerful tool for tumor evaluation. In addition, co-registration of PET studies performed at initial diagnosis and at various times after treatment are very beneficial for studying treatment effects and tumor recurrence. FDG-PET can also be useful in detecting malignant degeneration in low grade-tumors, which can be a great value in guiding stereotactic biopsy and surgery. In treatment of low grade tumors, PET studies with other tracers such as MET, FDOPA, FET, and FLT are emerging as superior to FDG-PET for detection of recurrent or residual tumors (Blake, Kalra, 2008, p. 87).
Currently FDG is the most widely used tracer in PET applications for the assessment of brain tumors, but other tracers are producing critical physiological, molecular and metabolic data about tumor pathophysiology. Studies with these agents have presented key information about tumor blood flow, oxygen utilization, hypoxia, amino acids metabolism, lipid synthesis and cell proliferation. Numerous studies have established that MET-PET (11C Methionine) is better for classifying tumor margin and for differentiating radiation necrosis. When FDG shows restrictions in target choice, MET is a good substitute because of its high specificity also MET is a superior alternative for PET guidance in neurosurgical procedures. The tracer MET is extremely sensitive for tumors detection and defining tumor borders, but of limited value for studying specific aspects of tumor biology. FET-PET (O-(2-[18F]fluroethyl)- L-tyrosine) has been shown to be a useful tracer for diagnosing recurrent glioma. There are other tracers (FDOPA & FLT) who are being researched for their clinical evaluation of brain tumors who will unlock critical information about tumor pathophysiology (Blake, Kalra, 2008, p. 80-81). A new disciple called Integrative Tumor Biology uses computational biology to further understand tumors and also is starting to generate parameters that produce predictive, personalized diagnosis and therapies for patients (Felipo, Llombart-Bosch, et. al., 2006, p. 96-97).
Advancements in molecular imaging have become the frontline in the fight to treat brain cancer. PET, in particular, has provided information into the inner workings of tumors giving doctors a better understanding of how to best combat this disease on a patient to patient basis. The continued development of complimentary tracers and the co-registration of PET with computed tomography and magnetic resonance imaging help doctors more accurately detect brain cancer and monitor response to therapy. These innovations are ultimately leading to a better diagnosis, treatment, and overall prognosis for brain cancer suffers.