Gallium Ga 68 dotatate is a radioactive diagnostic agent for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults and pediatric patients. NETs are rare benign or malignant tumors that develop in the hormone-producing cells of the body's neuroendocrine system, which are found in the stomach, intestines, pancreas, lungs, and other locations. NETs have receptors for somatostatin, a hormone that regulates the endocrine system. The uptake of gallium Ga 68 dotatate reflects the level of somatostatin receptor density in NETs. This uptake can also be seen in a variety of other tumor types or other pathologic conditions, or might occur as a normal variant. The uptake of gallium Ga 68 dotatate may need to be confirmed by histopathology or other assessments. Gallium Ga 68 dotatate was FDA-approved in June 2016.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to the administration of gallium Ga 68 dotatate. Patients should drink and void frequently during the first hours after administration to reduce radiation exposure.
NOTE: The radionuclide is not part of the kit. Before radiolabeling with gallium Ga 68, the contents of the kit are not radioactive. To minimize radiation exposure to occupational workers and patients, observe appropriate precautions that are consistent with proper patient management. Radiopharmaceuticals should only be used by nuclear physicians and/or radiopharmacists who are qualified by specific training and experienced in the safe use and handling of radioactive material, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radiopharmaceuticals.
NOTE: Storage and disposal should be controlled in compliance with appropriate regulations of the governmental agency authorized to license the use of radiopharmaceuticals.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration. The solution is clear and colorless; discard if the vial contains particulate matter or if the solution is discolored.
-To minimize radiation exposure, maintain adequate shielding during the life of the product.
-Use waterproof gloves during the entire handling and administration process.
-Dispose of any unused drug in a safe manner in compliance with applicable regulations.
Intravenous Administration
Preparation
-Consult product information for detailed instructions regarding preparation of the radionuclide.
-Storage: After addition of gallium Ga 68 chloride to the reaction vial, use Ga 68 dotatate injection within 4 hours.
Administration
-Using aseptic technique and radiation shielding, withdraw the appropriate dose immediately prior to administration.
-Assay the dose in a suitable dose calibrator.
-Administer via IV bolus injection.
-Initiate the positron emission tomography (PET) scan 40 to 90 minutes after administration.
-If case of extravasation, stop the injection, change the injection site, and irrigate the affected area with sodium chloride solution.
No serious adverse reactions were observed following use of gallium Ga 68 dotatate during clinical trials. However, nausea and vomiting have been reported during postmarketing use of the drug. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
No serious adverse reactions were observed following use of gallium Ga 68 dotatate during clinical trials. However, an injection site reaction (i.e., pain and burning sensation) has been reported during postmarketing use of the drug. Due to the voluntary nature of postmarketing reports, neither a frequency nor a definitive causal relationship can be established.
Hypersensitivity reactions after the administration of somatostatin receptor imaging agents have been noted in postmarketing reports. Reactions have predominantly consisted of cutaneous reactions, such as rash and pruritus, and have reversed either spontaneously or with routine symptomatic management. Less frequently, hypersensitivity reactions included angioedema or cases with features of anaphylaxis/anaphylactoid reactions.
Gallium Ga 68 dotatate should only be used by physicians or radiopharmacists who are qualified by training and experience in the safe use and handling of radioactive materials, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Care should be taken to assure minimal accidental exposure of radiation to occupational workers, including use of waterproof gloves and effective shielding. Furthermore, care should be taken to minimize radiation exposure to the patient through proper patient management before, during, and after the procedure. Advise patients to drink a sufficient amount of water to ensure adequate hydration prior to gallium Ga 68 dotatate administration, and instruct patients to drink and void frequently during the first hours after gallium Ga 68 dotatate administration to reduce radiation exposure. Also advise patients to avoid close contact with infants and pregnant women during the first 12 hours after administration of gallium Ga 68 dotatate.
The uptake of gallium Ga 68 dotatate reflects the level of somatostatin receptor density in neuroendocrine tumors (NETs); however, this uptake can also be seen in a variety of other tumor types (e.g., those derived from neural crest tissue). Increased uptake might also be seen in sites of splenosis or other pathologic conditions, including thyroid disease or subacute inflammation, or as a normal physiologic variant (e.g., uncinate process of the pancreas). Uptake may need to be confirmed by histopathology or other assessments. A negative scan after administration of gallium Ga 68 dotatate in patients who do not have a history of NETs, including in patients suspected of ectopic ACTH-secreting tumors, does not rule out the presence of NETs.
Extravasation may cause local irritation due to the acidic pH of gallium Ga 68 dotatate solution. In case of extravasation, stop the injection, change the injection site, and irrigate the affected area with sodium chloride solution.
There are no studies with gallium Ga 68 dotatate in women or animals during pregnancy, and its ability to cause fetal harm or affect the reproductive capacity is unknown. However, all radiopharmaceuticals have the potential to cause fetal toxicity, with the likelihood of harm depending on the stage of fetal development and the radiopharmaceutical dose.
There are no data available regarding the presence of gallium Ga 68 dotatate in human milk, the effect on the breastfed infant, or the effect on milk production. However, because of the potential for radiation exposure in a nursing infant, lactating mothers should temporarily interrupt breast-feeding and pump and discard breast milk for 12 hours after gallium Ga 68 dotatate administration.
For use with positron emission tomography (PET) imaging for localization of somatostatin receptor positive neuroendocrine tumors (NETs):
NOTE: This drug is a radiopharmaceutical and should only be administered by individuals specifically trained in the handling of radioactive material.
NOTE: Dosage measured in megabecquerels (MBq) and millicuries (mCi).
Intravenous dosage:
Adults: 2 MBq/kg (0.054 mCi/kg) by a single IV bolus; do not exceed 200 MBq (5.4 mCi). Images can be acquired 40 to 90 minutes after the bolus injection and must include a whole body acquisition from skull to mid-thigh. Adapt imaging acquisition delay and duration according to the equipment used and the patient and tumor characteristics to obtain the best possible image quality.
Infants, Children, and Adolescents: 2 MBq/kg (0.054 mCi/kg) by a single IV bolus; do not exceed 200 MBq (5.4 mCi). Images can be acquired 40 to 90 minutes after the bolus injection and must include a whole body acquisition from skull to mid-thigh. Adapt imaging acquisition delay and duration according to the equipment used and the patient and tumor characteristics to obtain the best possible image quality.
Neonates: 2 MBq/kg (0.054 mCi/kg) by a single IV bolus; do not exceed 200 MBq (5.4 mCi). Images can be acquired 40 to 90 minutes after the bolus injection and must include a whole body acquisition from skull to mid-thigh. Adapt imaging acquisition delay and duration according to the equipment used and the patient and tumor characteristics to obtain the best possible image quality.
Maximum Dosage Limits:
-Adults
2 MBq/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi) IV per procedure.
-Geriatric
2 MBq/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi) IV per procedure.
-Adolescents
2 MBq/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi) IV per procedure.
-Children
2 MBq/kg (0.054 mCi/kg) up to 200 MBq (5.4 mCi) IV per procedure.
-Infants
2 MBq/kg (0.054 mCi/kg) IV per procedure.
-Neonates
2 MBq/kg (0.054 mCi/kg) IV per procedure.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Albuterol; Budesonide: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Betamethasone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Budesonide: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Budesonide; Formoterol: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Corticosteroids (systemic): (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Corticotropin, ACTH: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Cortisone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Deflazacort: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Dexamethasone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Hydrocortisone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Lanreotide: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.
Methylprednisolone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Octreotide: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.
Pasireotide: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.
Prednisolone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Prednisone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Somatostatin analogs: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.
Triamcinolone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Vamorolone: (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors.
Gallium Ga 68 dotatate binds to somatostatin receptors, with greatest affinity for subtype 2 receptors (SSTR2). It binds to cells that express somatostatin receptors, including malignant cells, which over express SSTR2 receptors. Gallium 68 is a beta positive emitting radionuclide with an emission yield that allows positron emission tomography (PET) imaging. The uptake of gallium Ga 68 dotatate reflects the level of somatostatin receptor density in neuroendocrine tumors (NETs). This uptake can also be seen in a variety of other tumor types or other pathologic conditions, or might occur as a normal variant. The uptake of gallium Ga 68 dotatate may need to be confirmed by histopathology or other assessments.
Gallium Ga 68 dotatate is administered intravenously. Once administered, the drug distributes to all subtype 2 receptor (SSTR2) expressing organs such as pituitary, thyroid, spleen, adrenals, kidney, pancreas, prostate, liver, and salivary glands. There is no uptake in the cerebral cortex or in the heart; thymus and lung uptakes are usually low. A total of 12% of the injected dose is eliminated in the urine in the first 4 hours after administration.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
The amount of radiation absorbed following administration of 150 MBq (4.05 mCi) of gallium Ga 68 dotatate to an adult weighing 75 kg is approximately 3.15 mSv (0.021 mSv/MBq). Gallium Ga 68 dotatate decays with a half-life of 68 minutes.
-Special Populations
Pediatrics
For pediatric patients, the amount of radiation absorbed following gallium Ga 68 dotatate administration is estimated to be 0.35 mSv/MBq for neonate, 0.13 mSv/MBq for child 1 year, 0.064 mSv/MBq for child 5 years, 0.04 mSv/MBq for child 10 years, and 0.025 mSv/MBq for adolescent 15 years.