Following are some of the questions asked to Dr. Shamim Ahmed Shamim in our 222nd Sarcoma Support Group Meeting Session on Zoom.
What is PET Scan?
A PET/CT scan is a non-invasive diagnostic imaging tool that combines—Positron Emission Tomography (PET) and Computed Tomography (CT)—into one procedure. This combination allows doctors to obtain more detailed and accurate information about the inside of your body, particularly for diagnosing and managing diseases such as cancer, heart disease, and certain brain disorders.
PET scans detect metabolic activity in tissues. A small amount of radioactive material (called a radiotracer) is injected into the body. This tracer emits positrons (a type of subatomic particle) which undergoes annihilation by combining with negatively charged electrons, resulting in emission of two 511 keV photons in opposite directions. The PET scanner detects the emitted radiation and creates images showing areas of high metabolic activity, which often indicate the presence of disease, such as cancer
What is FDG UPTAKE?
FDG (Fluorodeoxyglucose) is an analog of glucose. It is taken up by living cells via cell membrane glucose transporters and subsequently incorporated into the first step of the normal glycolytic pathway. FDG is labeled with a radioactive isotope (fluorine-18), which allows it to be detected by the PET scanner. 18F-FDG accumulates in tissue proportional to the amount of glucose utilization. Increased consumption of glucose is characteristic of most cancers.
What is the meaning of SUV max?
It is the most widely used semi-quantitative parameter in PET/CT. It gives the relative concentration of the radiotracer in the ROI (region of interest) drawn on a lesion with respect to decay corrected injected dose of radiopharmaceutical/unit body weight.
SUV = activity concentration in tissue / injected activity/body size
SUVmax is the highest voxel value within the ROI.
What precautions one must take for going for PET CT? risk of radiation to small kids and how long to be isolated.
- Patient should be fasting for 4-6 hours.
- Good hydration
- S. Glucose level < 200 mg/dL
- The patient should be kept warm, and should be quiet and relaxed
- Void before scan
- Rule out pregnancy
- Stop breastfeeding for 8-12 hours after injection
- Sedation may be required
- Insulin should be stopped, in case of diabetic patients
- Prior history of RT/Chemotherapy/Surgery
- No need for isolation (As a precaution, one can avoid close contact with pregnant women, babies and young children (<5 years) for 6 hours after the scan).
- The radiation in the radioactive tracer is minimal.
References: Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54
In which sarcomas, are PET-CT done? both for low grade or high grade sarcomas
FDG PET/CT imaging is routinely performed on patients with sarcoma at the time of diagnosis, to evaluate response to systemic therapy, esp if progression/recurrence is suspected, to guide additional therapy. FDG PET/CT imaging provides a rapid and early overview of the metabolic activity of sarcomas and is extremely sensitive. While FDG PET/CT is highly sensitive for the diagnosis of osseous and soft tissue sarcomas, it should be noted that PET/CT is less sensitive for lower-grade sarcomas (strong correlation between the standardized uptake value (SUV) and tumor grade, i.e. higher the grade, higher the FDG uptake and vice versa).
References: Rakheja R, Probst S. FDG PET/CT as a marker for grading sarcomas and for the individualization of disease management. Imaging Med. 2013;5(1):75–81
What is the meaning of disease progression in PET CT
More than 30% increase in size and 18F-FDG SUL peak, with >0.8 SUL units increase in tumor SUL from baseline scan or, visible increase in the extent of 18F-FDG tumor uptake or, Appearance of new 18F-FDG avid lesions typical of cancer
How can help PET-CT in determining stage of cancer?
PET/CT is a non-invasive diagnostic imaging tool that includes imaging of the whole body (base of skull to mid-thigh or head to toe). Thus, it can help detect & assess primary tumors, nodal metastasis, as well as distant spread of disease.
How can PET-CT help in determining treatment options in sarcoma?
Sarcomas are a heterogeneous group of malignant tumors with variable clinical outcomes. Their presence in multiple body locations represents significant diagnostic and therapeutic challenges. FDG-PET can determine the tumor characteristics of high metabolism which is a reflection of the malignant nature of a tumor.
FDG-PET/CT can be used as part of the initial workup for the initial staging of sarcomas, esp. for detecting distant metastasis, differentiating between neurofibroma(s) and MPNST, and guiding biopsies from the most metabolically active part of the tumors. All these have implications in deciding treatment options (local vs systemic therapy) in patients with sarcoma.
FDG-PET/CT can also identify treatment response. Despite responding to neoadjuvant chemotherapy, these tumors may not change significantly in size but show decrease in metabolic activity. Being able to assess patient’s early response to chemotherapy may potentially guide management decisions. Progression/recurrence can also be detected early and change in therapy/additional therapy may be done.
(NCCN guidelines)
What is preferred PET CT or PET CT with contrast? Why contrast should be avoided in people with single kidney and elderly?
Routinely, PET/CT without contrast is done to avoid any contrast-related side effects. However, contrast administration benefits outweigh the risks in patients when the accurate extent of disease and relation with adjacent structures is required for staging/treatment purposes.
Renal function should be checked before contrast agent administration in all patients considered at risk of contrast agent nephrotoxicity. Routine creatinine testing prior to contrast agent administration is not necessary for all patients; the major indications are age > 60 years, history of preexisting renal disease or impairment (including dialysis, kidney transplant, single kidney, renal cancer, and renal surgery), history of DM/HTN, requiring medical therapy or use of metformin/metformin-containing drug combinations, as these patients are at a higher risk of contrast agent nephrotoxicity.
References: Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54
Why is PET scan CD required to be submitted?
If PET/CT studies are done outside of AIIMS, PET/CT study CD is required to be submitted for internal review. This allows our medical team to thoroughly evaluate your scans and ensure that your treatment plan is as accurate and effective as possible.
What happens in PET CT discussion and why are patients told to upload CD?
In the inter-departmental PET/CT discussions at AIIMS, New Delhi, patients’ scans/CDs are reviewed by expert faculties ensuring that any treatment-related queries are thoroughly discussed and addressed.
If patient is on targeted therapy like pazopanib and patients take sit early morning and has pet CT scheduled in the morning, is it fine to take pazopanib tablet on that day or one needs to skip medicine on that day?
Patients can take Tablet Pazopanib early morning with some plain water.
What is preferred CT CHEST or PET-CT?
CT Chest is the preferred imaging modality for detecting and following up lung metastasis.
On the other hand, PET/CT may be preferred as part of initial staging to differentiate between neurofibroma(s) and malignant peripheral nerve sheath tumor (MPNST), to help differentiate between WDLPS and dedifferentiated liposarcoma, in patients with RMS due to the possibility of nodal metastases, and in other sarcoma patients to detect unusual sites of distant metastasis. It also has an important role in determining response to systemic therapy.
What do you mean by metabolic activity?
Metabolic activity is the uptake of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET). FDG (Fluorodeoxyglucose) is an analog of glucose and is the most commonly used radiopharmaceutical in PET imaging. It is taken up by living cells via cell membrane glucose transporters and subsequently incorporated into the first step of the normal glycolytic pathway. 18F-FDG accumulates in tissue proportional to the amount of glucose utilization. Areas of high FDG accumulation i.e. high metabolic activity, often indicate the presence of disease, such as cancer.
References: Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54
What is FAPI? Is there some FAPI trial going on in AIIMS? Which sarcomas have FAPI avidity
Fibroblast Activation Protein (FAP) is a type II transmembrane serine protease, known for its overexpression in the stroma of many epithelial cancers, including over 90% of sarcomas. This protein is predominantly expressed in cancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment. The specific overexpression of FAP in tumor stroma, coupled with its limited presence in normal tissues, provides a unique opportunity for targeted imaging and therapy in sarcoma patients.
FAPI (Fibroblast Activation Protein Inhibitor), a small molecule inhibitor of FAP, can be radiolabeled (with 68Ga) and used as a PET tracer, providing high-contrast images due to the specific binding of FAPI to FAP-expressing cells.
FAPI PET imaging can accurately identify sarcomas and monitor their response to treatment. This finding is particularly significant given the inherent challenges associated with the diagnosis and treatment of sarcomas, which include their diverse histological subtypes and variable responses to therapy.
68 Ga-FAPI scans, as well as 177Lu-FAPI therapy, are being done at the Department of Nuclear Medicine, AIIMS, New Delhi on a regular basis (subject to availability of the radiopharmaceutical).
References: Giammarile F, Knoll P, Paez D, Estrada Lobato E, Calapaquí Terán AK, Delgado Bolton RC. Fibroblast Activation Protein inhibitor (FAPI) PET imaging in sarcomas: A new frontier in nuclear medicine. Semin Nucl Med. 2024;54(3):340–4.
If a female undergoes PET-CT, for how much time she needs to stay away from children as body emits radiation?
The ICRP does not recommend interruption of breastfeeding after FDG administration since little FDG is excreted in the milk. However, as the lactating breast accumulates FDG, it is suggested that contact between mother and child be limited for 12 h after injection of FDG to reduce the radiation dose that the infant receives from external exposure to radiation emitted by the mother.
Although, the radioactive tracer gives off very small levels of radiation that go away very quickly. As a precaution, one can avoid close contact with pregnant women, babies, and young children (<5 years) for 6-8 hours after the injection.
References : Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328–54
Role of PET CT in NF1 with MPNST
MPNSTs (malignant peripheral nerve sheath tumors) are aggressive soft tissue sarcomas (STS), accounting for 2–3% of all STS. Although MPNSTs are rare in the common population, NF1 patients have an 8–13% lifetime risk of developing an MPNST.
18F-FDG PET-CT, using SUVs & tumor-to-liver ratios as semi-quantitative metabolic imaging markers, has been increasingly used as a non-invasive diagnostic tool for the characterization of PNSTs in NF1 patients. 18F-FDG PET-CT offers adequate accuracy & sensitivity in detecting MPNSTs in patients with NF1. Differentiating benign from malignant tumors has important prognostic and therapeutic implications. MRI and CT can be used to determine the site & extent of a lesion and its relationship to surrounding structures but often do not allow precise discrimination between plexiform neurofibromas and those that have degenerated into MPNSTs.
In contrast to MRI or CT, 18F-FDG PET can yield metabolic information that is based on increased glucose metabolism of malignant lesions.
References:
Bredella MA, Torriani M, Hornicek F, Ouellette HA, Plamer WE, Williams Z, et al. Value of PET in the assessment of patients with neurofibromatosis type 1. AJR Am J Roentgenol. 2007;189(4):928–35.
Geitenbeek RTJ, Martin E, Graven LH, Broen MPG, Anten MHME, van der Pol JAJ, et al. Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients. J Neurooncol. 2022;156(3):559–67.
Role of PET CT in the biopsy of dedifferentiated component of liposarcoma
Distinguishing well-differentiated liposarcoma (WDLPS) from dedifferentiated liposarcoma (DDLPS) is essential given distinct treatment paradigms & chemo-sensitivity. WDLPS and DDLPS often coexist as heterogeneous tumors, but DDLPS can appear during progression or recurrence of a WDLPS. As these tumors can be large and heterogeneous, a traditional biopsy can often miss the high-grade DDLPS area within the tumor (percutaneous biopsy has a sensitivity of ~36%,
Reference: Ikoma N., Torres K. E., Somaiah N., et al. Accuracy of preoperative percutaneous biopsy for the diagnosis of retroperitoneal liposarcoma subtypes. Annals of Surgical Oncology. 2015;22(4):1068–1072.).
Even though CT characteristics are often helpful in differentiating WDLPS from DDLPS, this is not always obvious, and frequently, the pathology at surgery does not match what was expected based on CT imaging and biopsy. 18F-FDG PET/CT has high sensitivity & specificity for identifying the presence of dedifferentiated liposarcoma in the tumor (as areas of dedifferentiation often correlate with high FDG uptake) and thus PET guided biopsy has an important role in these tumors.
References: 1. Parkes A, Urquiola E, Bhosale P, Lin H, Watson K, Wang W-L, et al. PET/CT imaging as a diagnostic tool in distinguishing well-differentiated versus dedifferentiated liposarcoma. Sarcoma. 2020;2020:8363986.
Thank You to Dr. Shamin Ahmed Shamim and Dr. Sameer Rastogi for contributing this article.