Nuclear Oncology PDF

# 17 Nuclear Oncology ## Norman Bolus, Krystle Glasgow, and Ann Steves Cancer is the first or second leading cause of death in the United States. Accurate staging, assessment of therapy, and early detection of disease recurrence are essential to obtaining the best outcome for patients. Radioimmun...

# 17 Nuclear Oncology ## Norman Bolus, Krystle Glasgow, and Ann Steves Cancer is the first or second leading cause of death in the United States. Accurate staging, assessment of therapy, and early detection of disease recurrence are essential to obtaining the best outcome for patients. Radioimmunoscintigraphy, positron emission tomography (PET), and other types of imaging offer many options for assisting oncologists in treating patients and make nuclear medicine technologists important members of the team that treats patients with cancer. ## Gallium Imaging Gallium-67 (Ga)-citrate is most commonly used in imaging lymphoma to assess the extent of the disease, detect its progression, and monitor the patient's response to treatment. Othertumors, such as lung cancer and multiple myeloma, also concentrate this tracer. Patient preparation for gallium imaging may include oral laxatives or enemas, but the usefulness of these bowel preparations to clear activity from the bowel is still being debated. Relevant medical history includes recent surgery, chemotherapy, or diagnostic tests; any drugs that may change the biodistribution of 67Ga-citrate, such as iron therapy or gadolinium magnetic resonance contrast agents; areas of recent trauma or infection; and the results of other imaging tests. For adults, the suggested dosage of 67Ga-citrate is 5-10 mCi (185-370 megabecquerels [MBq]). Imaging takes place 48-72 hr after intravenous administration of the tracer. (See Chapter 16 for information about the biodistribution of 67Ga-citrate and other technical considerations.) Anterior and posterior images of the head, chest, and abdomen are obtained using either the spot-view or whole-body technique. Special views and single-photon emission computed tomography (SPECT) imaging may be performed as indicated. Delayed imaging beyond 72 hr is sometimes necessary. ## Indium-111 (111In) Capromab Pendetide 111In-capromab pendetide (ProstaScint) is a monoclonal antibody that is directed against prostate-specific membrane antigen (PSMA), an antigen that is secreted to a greater extent by malignant prostate cells than by nonmalignant cells. The antibody is tagged with 111In and injected into the patient to identify metastases from the primary prostate cancer. Because understaging the extent of disease occurs frequently in prostate cancer, 111In-capromab pendetide may be used in patients who have been newly diagnosed to stage the disease before surgery more accurately. After surgery or radiation therapy, it is used to detect recurrence or residual cancer in patients with rising PSA levels but no other evidence of disease. Relevant patient history includes previous therapy and surgery, recent laboratory results including PSA levels and human antimurine antibody (HAMA) titer, results of other imaging examinations, and prior history of allergies or allergic reactions. Because monoclonal antibodies are produced from mouse spleen cells, the patient's immune system may identify the monoclonal antibody as a foreign protein. The patient's immune system then begins to produce antibodies against the monoclonal antibody, a process called a HAMA response, which increases the possibility of an allergic response to a second administration of monoclonal antibody and decreases the likelihood of a second successful imaging procedure. For this reason, patients receiving a second administration of radiolabeled monoclonal antibodies may be tested for this antibody before tracer administration. Patient preparation includes laxatives beginning the day before imaging. Some sources recommend continuing laxatives for 4-5 days until imaging is completed. Some sources also recommend bladder catheterization and bladder irrigation before imaging to remove all residual radioactive urine from the field of view. Patients should also be encouraged to increase fluid intake for the duration of the examination. After the administration of approximately 5 mCi (185 MBq) of 111In-capromab pendetide, an early image of the abdomen and pelvis is obtained at 30 min to 4 hr to delineate the blood pool for use during interpretation. Alternatively, a SPECT blood pool image using technetium-99m (99mTc)-labeled red blood cells may be obtained simultaneously with the 111In images on day 4 or 5. Anterior and posterior spot views or whole-body imaging, including the skull to mid-femur, are performed 4-5 days after tracer administration, along with SPECT images of the abdomen and pelvis (Figure 17.2.). Normal biodistribution of 111In-capromab pendetide includes activity in the blood pool and blood-filled structures (liver, spleen, and penis), bone marrow, and large bowel. ## 111In-Pentetreotide 111In-pentetreotide (OctreoScan) is a form of octreotide. Octreotide is an analog of the hormone somatostatin. 111In-pentetreotide binds to somatostatin receptors on the surface of cells, concentrating in tumors with a high density of receptor sites. It is a peptide, which is the portion of an amino acid molecule that binds naturally to receptors on the cell surface. Somatostatin is a hormone concentrated in the hypothalamus, cerebral cortex, brain stem, gastrointestinal tract, and pancreas. Its functions include neurotransmission and inhibition of the release of growth hormone, insulin, glucagon, and gastrin and hormone production by certain types of tumors. Receptor sites for somatostatin are located in the anterior pituitary gland, pancreatic islet cells, lymphocytes, and certain types of tumors (brain, breast, and lung cancer and lymphoma). 111In-pentetreotide is approved for localizing primary and metastatic tumors originating from neuroendocrine cells, cells that contain somatostatin receptor sites. This includes many types of tumors, such as pituitary and endocrine tumors, paraganglioma, medullary thyroid carcinoma, carcinoids, and small-cell lung cancer. Relevant patient history includes type of primary tumor; results of other imaging studies and tumor marker assays; recent surgery, chemotherapy, radiation therapy, and octreotide therapy; and history of cholecystectomy. The patient should be well-hydrated for at least 24 hr after tracer administration. It is recommended that a mild laxative be given to the patient 24 hr before tracer administration and continue for 48 hr afterward to remove any radioactivity in the gastrointestinal tract. The patient should void immediately before imaging, because the tracer is eliminated from the body primarily through the genitourinary system. Imaging can begin 24-48 hr after the administration of 6 mCi (222 MBq) of activity. Because the purpose of the procedure is to visualize the unknown primary site of the cancer or to demonstrate the extent of the disease, anterior and posterior whole-body imaging should be performed (Figure 17.3). SPECT imaging may be performed as indicated by the activity. ## 99mTc-Depreotide 99mTc-depreotide (NeoTect*) is a synthetic peptide that binds to somatostatin receptors found in normal tissue and in many malignant tumors. It may not be commercially available for nuclear medicine in the United States, but it is used to evaluate certain lung nodules identified on a chest x-ray or CT to determine which should be biopsied to rule out lung cancer. If a single pulmonary nodule concentrates 99mTc-depreotide, there is a greater chance that the nodule is malignant. Relevant history includes the results of the chest x-ray or CT, other lung conditions, recent surgery, and any allergies or previous allergic reactions. The only preparation is that the patient should be well-hydrated before tracer administration and for the first few hours afterward. Anterior and posterior planar projections of the chest or chest SPECT are obtained 2-4 hr after intravenous administration of 15-20 mCi (555-740 MBq) of 99mTc-depreotide. The tracer should not be administered with total parenteral solutions through those intravenous lines. Normal biodistribution includes the kidneys, liver, spleen, and bone marrow. On SPECT images, the ends of the ribs, sternum, and spine may show tracer uptake more than normal or include the kidneys, liver, spleen, sternum, and bone marrow. ## 99mTc-Arcitumomab 99mTc-arcitumomab (CEA-Scan) is a fragment of an antibody that is expressed against carcinoembryonic antigen (CEA), an antigen that is secreted by most colorectal cancers and up to 75% of adenocarcinomas. The principle behind CEA imaging is that the labeled antibody fragment will bind to the CEA on the tumor, demonstrating small areas of metastases that are not easily visualized with other types of imaging modalities. 99mTc-arcitumomab is used for two main reasons in patients with colorectal cancer: (1) to monitor patients who have rising CEA levels but who do not have clinical symptoms of cancer recurrence and (2) to identify which patients may benefit the most from surgical resection of the primary tumor. In the latter group of patients, a surgical cure may be possible if the tumor has not spread. Extensive spread of the disease negates the appropriateness of surgery. Relevant patient history includes information about the primary tumor, previous surgery, location of colostomy site, results of other medical imaging examinations, and CEA and liver enzyme levels. The patient should be well hydrated before tracer administration to enhance tracer clearance. Imaging may be performed 2-5 hr after intravenous administration of 25-30 mCi (925–1110 MBq) of 99mTc-arcitumomab, although imaging times closer to 5 hr permit better blood clearance, with the potential for better tumor visualization. Anterior and posterior planar images of the head, chest, abdomen, and pelvis are obtained along with SPECT imaging of the chest and pelvis. The patient's bladder should be emptied immediately before pelvic imaging to prevent masking of disease close to the bladder. Catheterization of the patient may be indicated. The colostomy bag should also be changed before imaging, and the location of the colostomy site should be noted on an additional image of the abdomen. Delayed imaging of the chest or abdomen at 18-24 hr may be necessary to better delineate tumor uptake. Normal biodistribution of 99mTc-arcitumomab includes tracer uptake in the heart, lungs, major blood vessels, liver, spleen, kidneys, bowel, and bladder (Figure 17.4). Uptake at the colostomy site may be faint or as intense as that in the blood pool. ## Scintimammography Radionuclide breast imaging is performed in cases of an indeterminate x-ray mammogram, dense breast tissue, and suspected recurrence of breast cancer after surgery or radiation therapy and as an aid in treatment planning for breast cancer. 99mTc-sestamibi is taken up into breast tumors as a result of the increased blood flow and metabolic rate of the neoplastic cells. No special preparation of the patient is required. Pertinent medical history includes the results of prior x-ray mammograms, prior breast surgery or other therapy, lactation and pregnancy status of the patient, date of the last menstrual period, and any physical signs or symptoms the patient is experiencing. Scintimammography should not be performed within 2 weeks of a needle aspiration or within 4-6 weeks of a breast biopsy. Imaging involves administering 20-30 millicuries (740-1110 MBq) of 99mTc-sestamibi intravenously in the arm contralateral to the involved breast. If abnormalities are suspected in both breasts, the tracer should be administered into a vein in the foot. Imaging begins 5–10 min after the tracer is injected. Planar views of the anterior chest and axillae, and lateral views of each breast, are acquired. The lateral views are acquired with the patient in the prone position with the breast suspended; the contralateral breast is compressed under the patient against the table. The anterior view may be acquired with the patient upright or supine. If nodules can be palpated, additional images with markers placed over the areas of abnormality may be helpful). The markers should be placed after the patient has been positioned for imaging. Tables specially designed for breast imaging may be helpful in correctly positioning the patient and increasing patient comfort. Specialized cameras also are available specifically for scintimammography, including positron emission mammography (PEM). Normal biodistribution of 99mTc-sestamibi includes uptake in the salivary and thyroid glands, myocardium, liver, gallbladder, intestines, skeletal muscles, kidneys, and bladder (Figure 17.5). ## Lymphoscintigraphy Lymphoscintigraphy is a method by which the lymph drainage pattern can be mapped or a sentinel lymph node (SLN) can be identified by injecting radioactive particles within or under the skin. This technique is most commonly performed in patients with melanoma or breast cancer to identify the SLN - the node nearest to a tumor. If an SLN can be identified and excised, a sample of the node is viewed under a microscope to determine whether malignant cells from the tumor have spread into the lymph system, which will carry them to distant parts of the body. If the SLN is negative for malignant cells, extensive surgery to dissect the lymph nodes is not necessary. Lymphoscintigraphy is often performed several hours before surgery, so coordination with surgical stuff may be necessary to ensure that the patient is properly prepared for surgery. No special preparation is needed for the nuclear medicine examination. Relevant patient history includes information about the site and type of cancer and the results of other imaging examinations. Tracer uptake into the lymphatics is dependent, in part, on the particle size of the tracer. **99mTc-sulfur colloid is filtered through a 0.22 µm filter to obtain a preparation with smaller particles. Two to six injections around the lesion, totaling approximately 1 mCi (37 MBq), are introduced into the dermis. The injection sites may be numbed with a local anesthetic before injection of the tracer.** Imaging begins immediately. If no lymph nodes are observed, imaging is repeated at 45 min to 1 hr and at 30 to 45 min intervals until a lymph node is observed. Other imaging protocols may be preferred. To assist in pinpointing the location of a lymph node, it is helpful to perform a transmission scan of the area in question to produce a silhouette of the body or outlining the body with intravenous tubing containing **99mTc** (Figure 17.6). Contamination of the imaging site may occur if the tracer leaks out of the injection site. Technologists should be alert to this possibility, because the contamination may be misinterpreted as a lymph node. ## 99mTc tilmanocept A new radiotracer was approved by the U.S. Food and Drug Administration (FDA) in 2013 and received a positive statement from the European Medicines Agency in 2014: **99mTc-tilmanocept (Lymphoseek)**, a mannosyl diethylene triamine penta-acetate (DTPA) dextran that targets the CD206 receptor. The molecular size is 7 nm, but accumulation in SLNs is not dependent on particle size as with the other colloids. Tilmanocept binds to mannose receptors expressed by reticuloendothelial tissue including macrophages and dendritic cells in lymph nodes, which present it to T-cell lymphocytes in lymph nodes. The advantages of this tracer include rapid clearance from the injection depot and low accumulation in second-echelon nodes. This novel radiopharmaceutical might be of particular utility in patients with head and neck melanoma. Recommended dose is 18.5 MBq (0.5mCi) and is used the same way as filtered sulfur colloid in sentinel lymph node imaging. ## Tumor Imaging Using 18F-Fluorodeoxyglucose 18F-Fluorodeoxyglucose (F-FDG) is a positron-emitting radiopharmaceutical used for metabolic imaging and the tracer most commonly used for positron emission tomography (PET) imaging. Malignant cells take up F-FDG to a greater extent than do nonmalignant cells, making this tracer clinically useful for differentiating between benign and malignant disease, staging malignancies, detecting the recurrence of cancer, and monitoring a patient's response to therapy. Although F-FDG has been used to image many types of cancer, the Centers for Medicare and Medicaid Services have approved reimbursement only for specific clinical indications involving certain cancers. Relevant patient history includes recent surgery, chemotherapy, radiation therapy, results of other imaging examinations, diabetes status, and the patient's ability to cooperate by lying still for several hours and lying with arms overheard. Patient preparation includes fasting for at least 4 hr to minimize F-FDG uptake in certain organs, such as the heart. A laxative may be prescribed the night before imaging. Because tumor uptake is reduced if the patient is hyperglycemic, the blood glucose level may be checked with a glucometer before the tracer is administered. Imaging involves administering 5-20 millicuries (185-740 MBq) of 18F-FDG intravenously. During the waiting period before imaging, the patient should rest quietly since excessive movement can cause tracer uptake in muscles that may be misinterpreted as disease. Likewise, the patient may receive a mild sedative to help relax and avoid muscle uptake related to tension. Imaging begins 30-60 min later. Imaging protocols vary widely, depending on the type of imaging instrumentation available and the area of the body to be imaged. Both emission (delineating the distribution of 18F-FDG) and transmission (needed for attenuation correction) images are acquired. Image processing varies, depending on the type of equipment and software. Images are displayed in the three tomographic planes and may include both attenuation-corrected and -uncorrected images. Normal 18F-FDG tracer uptake is visualized in the brain, myocardium, liver, spleen, stomach, intestines, kidneys, and bladder. Areas of increased uptake can also be seen in areas of healing wounds, infections, and granulomatous tissue, as well as in malignancies (Figure 17.7). Certain patients may require bladder catheterization or diuretics to eliminate urinary tract activity that interferes with image interpretation. ## 18F-Fluciclovine (AXUMIN") 18F-Fluciclovine is a diagnostic agent indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated prostate specific antigen (PSA) levels following prior prostate cancer treatment. The recommended dosage is 370 MBq (10 mCi) given as an intravenous bolus injection, with imaging beginning 3-5 minutes post-injection. Imaging should be done from mid-thigh to base of skull with a total scan time of 20-30 minutes. ## Table 17.1 - Nuclear Oncology Section Procedure Review Table | Nuclear medicine examination | Radiopharmaceutical (generic name) | Route of administration | Imaging time post-tracer administration | |---|---|---|---| | Lymphoma | Gallium Citrate 5-10 mCi | IV | 48-72 hours | | Prostate-specific membrane antigen imaging | 111In-Capromab Pendetide 5 mCi | IV | 30 minutes-4 hours, delayed imaging 4-5 days | | Somatostatin neuroendocrine tumor imaging | 111In-Pentetretide 6 mCi | IV | 24-48 hours | | Somatostatin lung nodule imaging | 99mTc-Depreotide 15-20 mCi | IV | 2-4 hours | | Carcinoembryonic antigen colorectal and adenocarcinoma imaging | 99mTc-Arcitumomab 25-30 mCi | IV | 2-5 hours, 5 hours recommended | | Scintimammography | 99mTc-Sestamibi 20-30 mCi | subcutaneous | Immediately, 45 min-1 hr and 30-45 min thereafter if/as needed | | Lymphoscintigraphy | 99mTc-Filtered Sulfur Colloid 1 mCi | subcutaneous | 30-60 minutes | | PET tumor imaging | 18F-Fluorodeoxyglucose 5-20 mCi | IV | 30-60 minutes | | Recurrent prostate cancer imaging | 18F-Fluciclovine 10 mCi | IV bolus injection | 3-5 minutes |