Netspot

68Ga-DOTATATE · Kit · Intravenous

Prescription (Rx) 2 recalls

Uses

1 INDICATIONS AND USAGE NETSPOT, after radiolabeling with gallium-68, is indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients. NETSPOT, after radiolabeling with gallium-68, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients. ( 1 )

Dosage and administration

After radiolabeling, handle gallium Ga 68 dotatate injection with appropriate safety measures to minimize radiation exposure. ( 2.1 ) Instruct patients to drink a sufficient amount of water before administration, during the first hours following administration and to void frequently. ( 2.1 ) Recommended dose is 2 MBq/kg (0.054 mCi/kg) of body weight up to 200 MBq (5.4 mCi) administered as intravenous bolus injection. ( 2.2 ) See the Full Prescribing Information for detailed instructions on how to prepare gallium Ga 68 dotatate injection (e.g., radiolabeling). ( 2.3 ) 2.1 Radiation Safety Drug Handling After radiolabeling, handle the gallium Ga 68 dotatate injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ( 5.1 )] . Use waterproof gloves, effective radiation shielding and appropriate safety measures when preparing and handling gallium Ga 68 dotatate injection. Radiopharmaceuticals should be used by or under the control of physicians who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides. Patient Preparation Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to administration of gallium Ga 68 dotatate injection. Drink and void frequently during the first hours following administration to reduce radiation exposure. 2.2 Recommended Dosage and Administration Instructions In adults and pediatric patients, the recommended amount of radioactivity to be administered for PET imaging is 2 MBq/kg (0.054 mCi/kg) of body weight up to 200 MBq (5.4 mCi) by intravenous injection (bolus). Verify the injected radioactivity by measuring the radioactivity of the syringe containing the gallium Ga 68 dotatate injection with a dose calibrator before administration to the patient [see Dosage and Administration ( 2.4 )]. Ensure that the injected radioactivity is within ± 10% of the recommended activity. 2.3 Drug Preparation The NETSPOT kit is supplied as 2 vials [see Dosage Forms and Strengths ( 3 )] which allows for direct preparation of gallium Ga 68 dotatate injection with the eluate from one of the following generators (see below for specific instructions for use with each generator): Eckert & Ziegler GalliaPharm germanium-68/gallium-68 ( 68 Ge/ 68 Ga) generator IRE ELiT Galli Eo germanium-68/gallium-68 ( 68 Ge/ 68 Ga) generator The 68 Ge/ 68 Ga generators are not supplied with the NETSPOT kit. Components of the kit: Vial 1 (reaction vial with lyophilized powder) contains: 40 mcg dotatate, 5 mcg 1,10-phenanthroline; 6 mcg gentisic acid; 20 mg mannitol. Vial 2 (buffer vial) contains: 60 mg formic acid; 56.5 mg sodium hydroxide and water for injection. Ancillary supplies (not included in the kit): Ancillary supplies needed (not supplied in kit): 1 mL sterile plastic syringe, 5 mL sterile plastic syringe, non-metallic or silicone coated sterile needles (size 21 to 23G), 0.2 micron sterile vented filter. Prepare gallium Ga 68 dotatate injection according to the following aseptic procedure: a. Use suitable shielding to reduce radiation exposure. b. Wear waterproof gloves. c. Test periodically (weekly) the gallium-68 chloride eluate for germanium-68 breakthrough by suitable method. Germanium-68 breakthrough and other gamma emitting radionuclides should be ≤ 0.001%. d. Set the temperature of the shielded dry bath to 95°C (203°F) and wait for the temperature to reach the set point and stabilize. e. Prepare syringes for elution and radiolabeling steps per Table 1 below. f. Use non-metallic or silicone coated needles to minimize trace metal impurity levels. Radiolabeling of carrier molecules with gallium-68 chloride is very sensitive to the presence of trace metal impurities. g. Use 1 mL low dead space plastic syringe to precisely measure the adequate volume of reaction buffer to be added during preparation. Do not use glass syringe. h. Prior to piercing vial septums, flip the cap off and swab the top of the vial closure with alcohol to disinfect the surface, and allow the stopper to dry. Table 1. Solutions for Generator Elution and Radiolabeling Reaction Solutions for use with Eckert & Ziegler GalliaPharm generator Syringe Solution Purpose 5 mL sterile plastic syringe 5 mL of 0.1 N sterile HCl supplied by the generator manufacturer For elution of the generator 1 mL sterile plastic syringe Vial 2 buffer Calculate the volume (in mL) by multiplying the volume of HCl used for the elution of the generator in mL by its molarity: Reaction buffer volume in mL = HCl volume in mL x HCl molarity (5 mL x 0.1 N = 0.5 mL of reaction buffer). For radiolabeling reaction Solutions for use with IRE Galli Eo generator 5 mL sterile plastic syringe 3.9 mL sterile water for injection For preliminary dilution of Vial 1 1 mL sterile plastic syringe Vial 2 buffer Calculate the volume (in mL) by multiplying the volume of HCl used for the elution of the generator in mL by its molarity: Reaction buffer volume in mL = HCl volume in mL x HCl molarity (1.1 mL x 0.1 N = 0.11 mL of reaction buffer). For radiolabeling reaction i. Pierce the Vial 1 septum with a sterile needle connected to a 0.2 micron sterile vented filter (not supplied) to maintain atmospheric pressure within the vial during the radiolabeling process. j. Follow the generator specific radiolabeling procedures below. Then continue with the incubation step k. Radiolabeling with Eckert & Ziegler GalliaPharm generator Connect the male luer of the outlet line of the GalliaPharm generator to a sterile needle (size 21G to 23G). Connect Vial 1 directly to the outlet line of the GalliaPharm generator by pushing the needle through the rubber septum and place the vial in a lead shield container.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS NETSPOT is supplied as a multiple-dose kit, containing two vials for preparation of gallium Ga 68 dotatate injection: Vial 1 (reaction vial with lyophilized powder): 40 mcg of dotatate, 5 mcg of 1,10-phenanthroline, 6 mcg gentisic acid and 20 mg D-mannitol for injection as a white lyophilized powder in a 10 mL glass vial with light-blue flip-off cap Vial 2 (buffer vial): clear, and colorless reaction buffer solution (60 mg formic acid, 56.5 mg sodium hydroxide in approximately 1 mL volume) in a 10 mL olefin polymer vial with a yellow flip-off cap Gallium-68 is obtained from one of the following generators: Eckert & Ziegler GalliaPharm ( 68 Ge/ 68 Ga) generator IRE ELiT Galli Eo ( 68 Ge/ 68 Ga) generator After radiolabeling with gallium-68 and pH adjustment with Reaction Buffer, Vial 1 contains a sterile solution of gallium Ga 68 dotatate at a strength of up to 218 MBq/mL (5.89 mCi/mL). NETSPOT is supplied as a multiple-dose kit containing: Vial 1 (reaction vial with lyophilized powder) containing 40 mcg of dotatate. ( 3 ) Vial 2 (buffer vial) containing 1 mL of reaction buffer solution. ( 3 ) After radiolabeling with gallium-68 and pH adjustment with Reaction Buffer, Vial 1 contains a sterile solution of gallium Ga 68 dotatate at a strength up to 218 MBq/mL (5.89 mCi/mL). ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Radiation Risk : Gallium Ga 68 dotatate contributes to a patient’s overall long-term cumulative radiation exposure. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Restrict close contact with infants and pregnant women during the first 12 hours after administration of gallium Ga 68 dotatate. ( 5.1 ) Hypersensitivity Reactions : Most reported reactions were rash and pruritus and reversible either spontaneously or with routine symptomatic management. ( 5.2 ) Risk for Image Misinterpretation : The uptake of gallium Ga 68 dotatate can be seen in a variety of tumor types other than NETs (e.g., those derived from neural crest tissue), in sites of splenosis or other pathologic conditions, and as a normal physiologic variant (e.g., uncinate process of the pancreas). ( 5.3 ) 5.1 Radiation Risk Gallium Ga 68 dotatate contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling and preparation radiolabeling procedures to protect patients and health care workers from unintentional radiation exposure [see Dosage and Administration ( 2.1 )] . Avoid close contact with infants and pregnant women during the first 12 hours after administration of gallium Ga 68 dotatate injection. 5.2 Hypersensitivity Reactions Hypersensitivity reactions following administration of somatostatin receptor imaging agents predominantly consisted of cutaneous reactions, such as rash and pruritus. Reactions reversed either spontaneously or with routine symptomatic management. Less frequently hypersensitivity reactions included angioedema or cases with features of anaphylaxis. 5.3 Risk for Image Misinterpretation The uptake of gallium Ga 68 dotatate reflects the level of somatostatin receptor density in NETs. However, 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 (e.g., thyroid disease or subacute inflammation) or might occur as a normal physiologic variant (e.g., uncinate process of the pancreas). PET images with gallium Ga 68 dotatate should be interpreted visually and the uptake may need to be confirmed by histopathology or other assessments [see Dosage and Administration ( 2.7 )] . A negative scan after the 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.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity reactions [see Warnings and Precautions ( 5.2 )] Nausea, vomiting, and injection site pain and burning sensation were all reported during post-approval use. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience The safety of gallium Ga 68 dotatate was evaluated in three single center studies [see Clinical Studies ( 14 )] and in a survey of the scientific literature. No serious adverse reactions were identified. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of NETSPOT or other somatostatin receptor imaging agents. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug. Gastrointestinal Disorders: Nausea and vomiting General Disorders and Administration Site Conditions: Injection site pain and burning sensation Immune System Disorders: Hypersensitivity reactions, predominantly rash, pruritus, less frequently angioedema or features of anaphylaxis.

Drug interactions

Somatostatin Analogs : Somatostatin analogs competitively bind to the same somatostatin receptors as gallium Ga 68 dotatate and may affect imaging – image just prior to dosing with long-acting somatostatin analogs. ( 7.1 ) Glucocorticoids : Repeated administration of high doses of glucocorticoids prior to gallium Ga 68 dotatate administration may affect imaging. ( 7.2 ) 7.1 Somatostatin analogs Non-radioactive somatostatin analogs competitively bind to the same somatostatin receptors as gallium Ga 68 dotatate. Image patients with gallium Ga 68 dotatate PET just prior to dosing with long-acting analogs of somatostatin. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. 7.2 Glucocorticoids Glucocorticoids can down-regulate somatostatin subtype 2 receptors (SSTR2). Repeated administration of high doses of glucocorticoids prior to gallium Ga 68 dotatate administration may result in false negative imaging.

Use in specific populations

Lactation : Breast milk should be pumped and discarded for 12 hours after administration. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no studies with gallium Ga 68 dotatate in pregnant women to inform any drug-associated risks; however, radioactive emissions, including those from gallium Ga 68 dotatate, can cause fetal harm. Animal reproduction studies have not been conducted with gallium Ga 68 dotatate. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. 8.2 Lactation Risk Summary There is no information on the presence of gallium Ga 68 dotatate in human milk, the effect on the breastfed child, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for gallium Ga 68 dotatate injection and any potential adverse effects on the breastfed child from gallium Ga 68 dotatate injection or from the underlying maternal condition. Clinical Considerations Advise a lactating woman to interrupt breastfeeding and pump and discard breast milk for 12 hours after gallium Ga 68 dotatate administration in order to minimize radiation exposure to a breastfed child. 8.4 Pediatric Use The efficacy of gallium Ga 68 dotatate PET imaging in pediatric patients with neuroendocrine tumors is based on extrapolation from adult studies, from studies demonstrating the ability of gallium Ga 68 dotatate to bind to somatostatin receptors [see Clinical Pharmacology ( 12.1 )] , and from a published study of gallium Ga 68 dotatate PET imaging in pediatric patients with somatostatin receptor positive tumors. The safety profile of gallium Ga 68 dotatate is similar in adult and pediatric patients with somatostatin receptor positive tumors. The recommended gallium Ga 68 dotatate injection dose in pediatric patients is weight based as in adults [see Dosage and Administration ( 2.2 )] . 8.5 Geriatric Use Clinical studies of gallium Ga 68 dotatate injection did not include sufficient numbers of subjects aged 65 and over, to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary There are no studies with gallium Ga 68 dotatate in pregnant women to inform any drug-associated risks; however, radioactive emissions, including those from gallium Ga 68 dotatate, can cause fetal harm. Animal reproduction studies have not been conducted with gallium Ga 68 dotatate. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

Pediatric use

8.4 Pediatric Use The efficacy of gallium Ga 68 dotatate PET imaging in pediatric patients with neuroendocrine tumors is based on extrapolation from adult studies, from studies demonstrating the ability of gallium Ga 68 dotatate to bind to somatostatin receptors [see Clinical Pharmacology ( 12.1 )] , and from a published study of gallium Ga 68 dotatate PET imaging in pediatric patients with somatostatin receptor positive tumors. The safety profile of gallium Ga 68 dotatate is similar in adult and pediatric patients with somatostatin receptor positive tumors. The recommended gallium Ga 68 dotatate injection dose in pediatric patients is weight based as in adults [see Dosage and Administration ( 2.2 )] .

Geriatric use

8.5 Geriatric Use Clinical studies of gallium Ga 68 dotatate injection did not include sufficient numbers of subjects aged 65 and over, to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Overdosage

In the event of a radiation overdose, the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by reinforced hydration and frequent bladder voiding. A diuretic might also be considered. If possible, an estimate of the radioactive dose given to the patient should be performed.

Description

11 DESCRIPTION NETSPOT is supplied as a sterile, multiple-dose kit for preparation of gallium Ga 68 dotatate injection for intravenous use. Dotatate, also known as DOTA-0-Tyr3-Octreotate, is a cyclic 8 amino acid peptide with a covalently bound chelator (dota). The peptide has the amino acid sequence: H-D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-OH, and contains one disulfide bond. Dotatate has a molecular weight of 1435.6 Daltons and its chemical structure is shown in Figure 3. Figure 3. Chemical Structure of Dotatate [(4,7,10-Tricarboxymethyl-1,4,7,10-tetrazacyclododec-1-yl)acetyl]-(D)-Phenylalanyl-(L)Cysteinyl-(L)-Tyrosyl-(D)-Tryptophanyl-(L)-Lysyl-(L)-Threoninyl-(L)-Cysteinyl-(L)-Threonine-cyclic(2-7)disulfide NETSPOT is a kit with the following components: Vial 1 (reaction vial with lyophilized powder) contains: 40 mcg dotatate, 5 mcg 1,10-phenanthroline; 6 mcg gentisic acid; 20 mg mannitol. Vial 2 (buffer vial) contains: 60 mg formic acid; 56.5 mg sodium hydroxide and water for injection. After radiolabeling, [see Dosage and Administration ( 2.3 )] , gallium Ga 68 dotatate injection also contains hydrochloric acid as an excipient derived from the generator eluate. The prepared gallium Ga 68 dotatate injection for intravenous use, is a sterile, pyrogen free, clear, colorless, buffered solution, with a pH between 3.2 and 3.8. Table 5, Table 6, and Table 7 display the principal radiation emission data, radiation attenuation by lead shielding, and physical decay of gallium-68. Table 5. Principal Radiation Emission Data (> 1%) Radiation/Emission % Disintegration Mean energy (MeV) beta+ 88% 0.8360 beta+ 1.1% 0.3526 gamma 178% 0.5110 gamma 3% 1.0770 X-ray 2.8% 0.0086 X-ray 1.4% 0.0086 Table 6. Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding Shield thickness (Pb) mm Coefficient of attenuation 6 0.5 12 0.25 17 0.1 34 0.01 51 0.001 Table 7. Physical Decay Chart for Gallium-68 Minutes Fraction remaining 0 1.000 15 0.858 30 0.736 60 0.541 90 0.398 120 0.293 180 0.158 360 0.025 Figure 3. Chemical Structure of dotatate

Mechanism of action

12.1 Mechanism of Action Gallium Ga 68 dotatate binds to somatostatin receptors, with highest affinity for subtype 2 receptors (SSTR2). It binds to cells that express somatostatin receptors, including malignant cells, which overexpress SSTR2. Gallium-68 is a β+ emitting radionuclide with an emission yield that allows PET imaging.

How supplied

16.1 How Supplied NETSPOT is supplied as a multiple-dose kit (NDC# 69488-001-40) for preparing multiple doses of gallium-68 radiolabeled dotatate injection. The kit contains: Vial 1 (10-mL Ultra inert Type I Plus glass vial, light-blue flip-off cap): 40 mcg of dotatate, 5 mcg 1,10-phenanthroline, 6 mcg gentisic acid, 20 mg mannitol as lyophilized powder (NDC# 69488-001-04) Vial 2 (10-mL cyclic olefin polymer vial, with a yellow flip-off cap): reaction buffer solution (approximately 1 mL volume), 60 mg formic acid, 56.5 mg sodium hydroxide and water for injection (NDC# 69488-001-01) The radionuclide is not part of the kit. Before radiolabeling with gallium-68, the contents of this kit are not radioactive. Expiry date is indicated on the original outer packaging, and on the vials. This medicinal product must not be used beyond the date indicated on the packaging. 16.2 Storage and Handling For prolonged storage, store NETSPOT in its original packaging at room temperature below 25°C (77°F) (do not freeze). After radiolabeling [see Dosage and Administration ( 2.3 )] with activities of up to 1,110 MBq (30 mCi), keep gallium Ga 68 dotatate injection upright with an appropriate shielding to protect from radiation, at a temperature below 25°C (77°F) (do not freeze), and use within 4 hours. The storage of the radiolabeled product must comply with regulatory requirements for radioactive materials. 16.1 How Supplied NETSPOT is supplied as a multiple-dose kit (NDC# 69488-001-40) for preparing multiple doses of gallium-68 radiolabeled dotatate injection. The kit contains: Vial 1 (10-mL Ultra inert Type I Plus glass vial, light-blue flip-off cap): 40 mcg of dotatate, 5 mcg 1,10-phenanthroline, 6 mcg gentisic acid, 20 mg mannitol as lyophilized powder (NDC# 69488-001-04) Vial 2 (10-mL cyclic olefin polymer vial, with a yellow flip-off cap): reaction buffer solution (approximately 1 mL volume), 60 mg formic acid, 56.5 mg sodium hydroxide and water for injection (NDC# 69488-001-01) The radionuclide is not part of the kit. Before radiolabeling with gallium-68, the contents of this kit are not radioactive. Expiry date is indicated on the original outer packaging, and on the vials. This medicinal product must not be used beyond the date indicated on the packaging. 16.2 Storage and Handling For prolonged storage, store NETSPOT in its original packaging at room temperature below 25°C (77°F) (do not freeze). After radiolabeling [see Dosage and Administration ( 2.3 )] with activities of up to 1,110 MBq (30 mCi), keep gallium Ga 68 dotatate injection upright with an appropriate shielding to protect from radiation, at a temperature below 25°C (77°F) (do not freeze), and use within 4 hours. The storage of the radiolabeled product must comply with regulatory requirements for radioactive materials.

Patient information

Adequate Hydration Advise patients to drink a sufficient amount of water to ensure adequate hydration before their PET study and urge them to drink and urinate as often as possible during the first hours following the administration of gallium Ga 68 dotatate injection, in order to reduce radiation exposure [see Dosage and Administration ( 2.3 )] . Lactation Advise a lactating woman to interrupt breastfeeding and pump and discard breast milk for 12 hours after gallium Ga 68 dotatate injection administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations ( 8.2 )] . Close Contact Advise patients to avoid close contact with infants and pregnant women during the first 12 hours after administration of gallium Ga 68 dotatate. Distributed by: Advanced Accelerator Applications USA, Inc. Millburn, NJ 07041 ©2023 Advanced Accelerator Applications USA, Inc. NETSPOT ® is a registered trademark of Novartis AG and/or its affiliates. T2023-68

Label text from the FDA structured product label by Advanced Accelerator Applications USA, Inc (revised Jul 6, 2026). Long sections are shortened; the complete label is on DailyMed.

Netspot NDC products (1)

NDC	Strength & form	Labeler	Type
69488-001	Kit	Advanced Accelerator Applications USA, Inc	NDA

Netspot recalls

D-0747-2022 Apr 13, 2022 · Class III · Terminated
Subpotent Drug: low out-of-specification results for Vial 1 assay obtained during stability studies.
D-0799-2020 Jan 29, 2020 · Class II · Terminated
Defective Container: loose aluminum cap crimp for the dilution buffer vial present in the NETSPOT Kit (vial 2).

Frequently asked questions

What is Netspot used for?

What are the side effects of Netspot?

Who makes Netspot?

Netspot is listed by 1 labeler in the FDA NDC directory, including Advanced Accelerator Applications USA, Inc.

Has Netspot been recalled?

The FDA enforcement database lists 2 recalls for Netspot, most recently D-0747-2022 (class iii): Subpotent Drug: low out-of-specification results for Vial 1 assay obtained during stability studies.