Feb 7, 2024
Characterization Of Indeterminate Lesions
Other Radiotracers - Thymidine 3-deoxy-3-18fluorothymidine (flt)
PET-MRI
PET CT is one of the recent modalities useful for the diagnosis of patients with cancer, especially for identifying distant metastatic areas. It is important to understand the distant metastatic areas because after giving treatment therapies like chemotherapy, chemoradiation, or surgery, it becomes necessary to understand the sites of residual tumor or recurrence in tumor growth.
Fluorodeoxyglucose is the radiotracer given for the PET CT. Tumor cells quickly take it up because they are metabolically active, proliferating cells. When we club this with anatomical imaging like a CT scan, we can understand which areas of the body have an increase in fluorodeoxyglucose uptake, thus helping us identify distant tumor sites. PET CT scan helps us in planning the radiation for tumors.
Nodal and distal metastasis is better understood by using PET CT, while other investigations like plain CT / MRI can be used to identify the primary sites of tumors. Additionally, in occult or hidden cancer, carcinomas with unknown primary sites, and in cases of micrometastasis (metastasis <2 mm), PET CT will help in the early diagnosis of these tumors.
A CT scan helps to understand the events happening at the anatomical level. But for the molecular level/ cellular level imaging, the PET scan is a more useful investigation. We can easily identify the areas of increased uptake of the radioisotope in PET scans. Positron emission tomography (PET) scan - These positrons are taken up by the tumor cells which will help us to understand the actively proliferating tumor areas. A CT will help in getting the anatomical imaging, while a PET scan will help to get the metabolic activity in tumor cases.
This scan will help in getting both the anatomical imaging plus the metabolically active imaging. When we see an increased fluorescence in anatomical tumor areas, we can tell that this is a metabolically active lesion. Important information box Causes of increased metabolic activity Infection Inflammation Cancer Tuberculosis
The CT component of PET-CT has two important functions: Facilitates precise anatomical location of radiotracer activity - more exact anatomical localization of pathology, more accurate distinction between pathology and normal appearances. The CT component is an accurate measurement of radioisotope uptake. CT is usually performed with a lower dose of radioisotope than conventional diagnostic CT. PET CT is commonly performed without IV contrast as it can result in PET artifacts.
Recently, similar to CT, manufacturers have introduced continuous bed motion PET acquisition systems with the potential for fewer artifacts and increased sensitivity. If a PET scan is done alone, you can identify lesions having increased radioactive isotopes. However, we cannot understand the exact relation between the lesion and other neighboring blood vessels or lobes/ any other nearby organ. If we do a PET CT, we can clearly understand the relationship of the lesion with the neighboring blood vessels, organs, and tissues. The treatment plan will also vary according to the PET imaging.
PET relies on a radioactive molecule ( radiotracer) that decays with positron emission. The radiotracer is given intravenously to the patient which is actively taken up by the cells. The cell recognizes it as a foreign body and tries to destroy it. As a consequence, it gets trapped in its metabolic pathway and hence will emit positrons.
Malignant cells trap more radiotracer compared to non-malignant cells. Hence the positron emission will be more from malignant cells because of the decaying process. These positron emissions will be easily identified using PET-CT. Positrons travel for a short distance in tissues before colliding with electrons. When they collide, the annihilation reaction results in two photons also known as gamma rays, and these are emitted at approximately 180 degrees to each other. We try to identify these gamma rays around lesions.
Whenever we give an FDG, it is taken up by the cell and normally it goes into FDG-6P and then goes into decaying. If the cell is malignant, FDG is recognized as a foreign cell and will go into destruction. During the destruction, the FDG will emit a positron, which will collide with electrons and will lead to an annihilation reaction, and will release two photons. These photons are detected by opposing detectors. The computer reassembles these signals will be combined to form an image.
The standardized uptake value (SUV) which provides a semi-quantitative index of radiotracer uptake is widely used in clinical PET: Important information box SUV = Tracer uptake (MBq/mL) / Administered activity(MBq)/ patient weight(kg) * 1000 Depending on the radiotracer used, different aspects of tissue metabolism can be studied such as - Distribution of blood flow Oxygen utilization Protein synthesis Glucose metabolism Cancer cells have higher metabolic activity than normal cells and hence will have more glucose metabolism. FDG helps us to identify which cells are having increased metabolic activity.
FDG PET-CT detects an unexpected primary site. FDG PET-CT is superior to FDG PET. It improves diagnosis by contributing directly to detecting unexpected nodal and unexpected distant metastasis. It detects occult synchronous cancers like silent lung and colorectal cancers. A CT scan will show the primary lesion of abnormality. Compared to simple FDG PET, it will show a lesion with an increased radioisotope uptake but with the integration of CT, we will be able to understand not just the anatomical location, but also the primary site, any other nodal/regional metastasis or even a distant metastasis throughout the body.
A limited use in staging the primary site. Limited assessment of nodal disease It can detect the majority of clinically visible primary tumors. Useful to delineate primary tumors where submucosal extension of disease is a feature, such as post-cricoid carcinoma and tracheal carcinoma We cannot differentiate subclinical disease and reactive nodes, so it cannot help decide elective neck treatment.
Hence, we cannot differentiate between malignant disease and infective pathology. In those patients having moderate to high risk of neck metastasis, a positive FDG PET-CT scan will be highly indicative of neck nodal disease. In patients with low risk, a negative FDG PET-Ct will be highly indicative of no nodal disease.
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FDG PET-CT is accurate at detecting recurrent disease. It is effectively superior to CT and MRI for distinguishing active disease from treatment sequelae in people who develop symptoms during follow-up. It is more accurate in the assessment of recurrence after previous curative treatment for head and neck squamous cell carcinoma.
If lesions found on CT/MRI seem to be confusing, whether malignant or non-malignant, a PET-CT will be a key investigation for making the current diagnosis. Indeterminate lesions are commonly found in the lung, liver, and adrenal glands, the lungs being the commonest site. FDG PET-CT is an accurate investigation in diagnosing pulmonary lesions. Lesions > 1 cm = can be detected by FDG PET-CT because it is dependent on the avidity of the lesion. Will help in the detection of synchronous other head neck and lung cancers.
Pre-treatment FDG PET-CT uptake at the primary site and within involved nodes is an independent predictor of subsequent prognosis. Higher uptake means poorer prognosis, and lower uptake means better prognosis.
It has been shown to predict an early-on response to neoadjuvant chemotherapy in various solid tumors including oesophageal carcinoma.
It is increasingly used for radiotherapy target volume delineation. Benefits include Inter-observer variation in gross tumor volume can be reduced Identification of geographical misses of tumor lesions. Disadvantages include - Inflammation secondary to biopsy/surgery can lead to over-estimation of tumor volume, which in turn causes overdosage of radiation. There is no universally accepted, standardized method of identifying tumor margins unless there is a pathological examination.
Limited value in pre-operative assessment of thyroid nodules because both malignant and benign cells can equally uptake FDG. Important in the assessment of post-operative treatment of differentiated thyroid cancer.
Useful for pre-treatment staging, to detect residual/recurrent tumor. Cannot reliably distinguish malignant or benign salivary tumors. Can help in distinguishing between sequelae of treatment and recurrence of tumor.
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Difficult to distinguish between brown adipose tissue from adjacent small FDG avid nodes. Skeletal muscle will uptake FDG in a linear symmetrical way Pre-vertebral muscle will asymmetrically have an FDG uptake, normally being symmetrical. Waldeyer’s ring will have an FDG uptake similar to FDG uptake by occult primary tumors arising at these sites. Dental amalgam causes an FDG uptake in the anterior two-thirds of the mouth.
Branchial cyst Vs necrotic nodes FDG uptake present in the wall of lesion - Branchial cyst is the confirmed diagnosis No FDG uptake present in the wall of the lesion -. Diagnosis is inconclusive. Lung cancer Adenocarcinoma - may not have FDG uptake Small subcentric lung metastasis - may not have FDG uptake Granulomatous diseases Differentiation between sarcoid-like reaction and cancerous nodes is difficult in FDG-avid chest nodes. In normal-sized nodes at the paratracheal or subcarinal region, there is an FDG uptake, this will favor sarcoidosis/ tuberculosis/ any other granulomatous disease. If a neck node is enlarged and is seen in the hila/paratracheal region, we can think of cancer in these cases.
Positive FDG PET-CT = High suspicion of disease excluding infective cause Negative FDG PET-CT = Absence of active disease, demands careful surveillance.
Useful to differentiate between lung metastasis and benign lesions Effective for detecting residual disease after RT To predict the outcome between RT and chemo-RT
Tumor cells are sometimes hypoxic and hypoxic cells are radioresistant. Hence, detecting hypoxic lesions is most important. Hypoxic cells require three times more radiation as compared to non-hypoxic cells. But that much dosage will damage all the surrounding healthy tissue. Hence, these radiotracers will help in detecting only the hypoxic cells and then we can apply RT only to the sub volume of these cells. Important information box Radiotracers detecting hypoxia - Fluorinated nitroimidazole compounds Copper isotopes of varying half-life like 60Cu, 62Cu FMISO is the best-validated hypoxic cell tracer For imaging to be perfect, FMISO has to be given 2-3 hours before imaging as it requires a longer duration to diffuse in body cells.
Improved delineation of orbital and skull involvement in nasopharyngeal cancer.
There is less risk of ionizing radiation, but no other advantages as compared to PET-CT scan.
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