Netspot

Name: Netspot

Commonly used brand name(s)

In the U.S.

  • Netspot

Available Dosage Forms:

  • Solution

Therapeutic Class: Diagnostic Agent, Radiopharmaceutical Imaging

Before Using Netspot

In deciding to use a diagnostic test, any risks of the test must be weighed against the good it will do. This is a decision you and your doctor will make. Also, other things may affect test results. For this test, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of gallium Ga 68 dotatate injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of gallium Ga 68 dotatate injection in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Netspot Dosage and Administration

Radiation Safety

Drug Handling
After reconstitution and radiolabeling, handle the 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 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 Ga 68 dotatate. Drink and void frequently during the first hours following administration to reduce radiation exposure.

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 of body weight (0.054 mCi/kg) up to 200 MBq (5.4 mCi). 

After reconstitution with Ga 68 chloride eluate from an Eckert & Ziegler GalliaPharm Germanium 68/Gallium 68 (Ge 68/Ga 68) generator and buffer, [see Drug Preparation (2.3) ], administer Ga 68 dotatate by intravenous injection (bolus).

Verify the injected radioactivity by measuring the radioactivity of the vial containing the Ga 68 dotatate injection with a dose calibrator before administration to the patient [see Administration (2.4) ]. Ensure that the injected radioactivity is within ±10% of the recommended dose.

Drug Preparation

The Netspot kit is supplied as 2 vials and an accessory cartridge [see Dosage Forms and Strengths (3) ] which allows for direct preparation of Ga 68 dotatate injection with the eluate from an Eckert & Ziegler GalliaPharm Germanium 68/Gallium 68 (Ge 68/Ga 68) generator. The Eckert & Ziegler GalliaPharm Ge 68/Ga 68 generator (“GalliaPharm generator”) is not supplied with the Netspot kit. The safety and efficacy of the Ga 68 dotatate injection drug product prepared from the Netspot kit has been established only when using a Ga 68 chloride solution eluted from the GalliaPharm generator.

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.
  • Accessory cartridge contains: 660 mg porous silica. The accessory cartridge reduces the amount of Ge 68 potentially present in generator eluate.

Prepare Ga 68 dotatate for intravenous injection according to the following aseptic procedure (Figure 1):

  1. Use suitable shielding to reduce radiation exposure.
  2. Wear waterproof gloves.
  3. Set the temperature of the shielded dry bath to 203 °F (95 °C), and wait for the temperature to reach the set point and stabilize.
  4. Prepare a syringe containing 5 mL of 0.1 N sterile HCl, to be used for elution of the GalliaPharm generator. Use 0.1N sterile HCl supplied by the generator manufacturer. Test periodically (weekly) the Ga 68 chloride eluate for Ge 68 breakthrough by suitable method. Ge 68 breakthrough and other gamma emitting radionuclides should be ≤ 0.001%. The Ga 68 chloride is sterile as eluted from the GalliaPharm generator.
  5. Remove the cap from Vial 1 (reaction vial), swab the top of the vial with alcohol to disinfect the surface, and allow the stopper to dry.
  6. Pierce the Vial 1 septum with a sterile needle connected to a 0.22 micron sterile vented filter (not supplied) to maintain atmospheric pressure within the vial during the reconstitution process.
  7. Remove the cap from the Vial 2 (buffer vial), swab the top of the vial with alcohol to disinfect the surface, and allow the stopper to dry.
  8. Using a 1 mL sterile syringe, withdraw the required volume of the reaction buffer from Vial 2. 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 (for the GalliaPharm generator eluate, 5 mL x 0.1 N = 0.5 mL of reaction buffer).
  9. Connect the top of the cartridge to the male luer of the outlet line of the GalliaPharm generator. Connect the bottom of the cartridge with a sterile needle.
  10. Connect Vial 1 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.
  11. Elute the generator directly into the Vial 1 through the cartridge and the needle according to the instructions for use of the GalliaPharm generator that are supplied by Eckert & Ziegler, in order to reconstitute the lyophilized powder with 5 mL of eluate. Perform the elution manually or by means of a pump.
  12. At the end of the elution, disconnect the generator from Vial 1 by removing the needle from the rubber septum, and immediately (do not delay buffer addition more than 10 min) add the kit reaction buffer in the 1 mL sterile syringe (the amount of reaction buffer was determined from Step h). Withdraw the syringe and the 0.22 micron sterile air venting filter, and then using a tong, move Vial 1 to the heating hole of the dry bath, and leave the vial at 203 °F (95 °C, not to exceed 98 °C) for at least 7 minutes (do not exceed 10 minutes heating) without agitation or stirring. Do not invert or shake the reaction vial because contact between the solution and the rubber septum can lead to zinc leaching and can interfere with binding of Ga 68 to the peptide.
  13. After 7 minutes, remove the vial from the dry bath, place it in an appropriate lead shield and let it cool down to room temperature for approximately 10 minutes.
  14. Assay the whole vial containing the Ga 68 dotatate injection for total radioactivity concentration using a dose calibrator and record the result.
  15. Perform the quality controls according to the recommended methods in order to check the compliance with the specifications [see Dosage and Administration (2.5)].
  16. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
  17. Keep the vial containing the Ga 68 dotatate injection upright in a radio-protective shield container at a temperature below 77 °F (25 °C) until use.
  18. After addition of Ga 68 chloride to the reaction vial, use Ga 68 dotatate injection within 4 hours.

 Administration

Prior to use, visually inspect the prepared Ga 68 dotatate injection behind a lead glass shield for radioprotection purposes. Only use solutions that are clear without visible particles. Using a
single-dose syringe fitted with a sterile needle and protective shielding, aseptically withdraw the prepared Ga 68 dotatate injection prior to administration. Measure the total radioactivity in the syringe by a dose calibrator immediately prior to administration. The dose calibrator must be calibrated with National Institute of Standards and Technology (NIST) traceable standards.

Handle and dispose radioactive material in accordance with applicable regulations.

Specifications and Quality Control

Perform the quality controls in Table 1 behind a lead glass shield for radioprotection purposes.

Table 1 Specifications of the Radiolabeled Imaging Product (Ga 68 dotatate)

Test

Acceptance Criteria

Method

Appearance

Colorless and particulate free

Visual Inspection

pH

3.2 – 3.8

pH-indicator strips

Labeling Efficiency

Ga 68 dotatate ≥  92% and Other Ga 68 species ≤ 5%

Thin layer chromatography (ITLC, see details below)

Determine labeling efficiencyof Ga 68 dotatate:

Obtain the following materials:

  • ITLC SA or ITLC SG.
  • Ammonium acetate 1M: Methanol(1:1 V/V)
  • Developing tank
  • Radiometric ITLC scanner

Perform the following:

  1. Pour ammonium acetate 1M: Methanol (1:1 V/V) solution to a depth of 3 to 4 mm in the developing tank, cover the tank, and allow it to equilibrate.
  2. Apply a drop of the Ga 68 dotatate injection on a pencil line 1 cm from the bottom of the ITLC strip.
  3. Place the ITLC strip in the developing tank and allow it to develop for a distance of 10 cm from the point of application (i.e. to the top pencil mark).
  4. Scan the ITLC with a radiometric ITLC scanner
  5. Calculate radiochemical purity (RCP) by integration of the peaks on the chromatogram. Do not use the reconstituted product if the RCP is less than 92%.
  6. The retention factor (Rf) specifications are as follows for ITLC SA or ITLC SG:
    ITLC SA: Non-complexed Ga 68 species, Rf = 0 to 0.1; Ga 68 dotatate, Rf = 0.6 to 0.8
    ITLC SG: Non-complexed Ga 68 species, Rf = 0 to 0.1; Ga 68 dotatate, Rf = 0.8 to 1

Image Acquisition

For Ga 68 dotatate PET imaging, the acquisition must include a whole body acquisition from skull to mid-thigh. Images can be acquired 40 to 90 minutes after the intravenous administration of the Ga 68 dotatate. Adapt imaging acquisition delay and duration according to the equipment used, and the patient and tumor characteristics, in order to obtain the best image quality possible.

Image Interpretation

Ga 68 dotatate binds to somatostatin receptors. Based upon the intensity of the signals, PET images obtained using Ga 68 dotatate indicate the presence and density of somatostatin receptors in tissues. Tumors that do not bear somatostatin receptors will not be visualized. Increased uptake in tumors is not specific for NET  [see Warnings and Precautions (5.2)] .

Radiation Dosimetry

Estimated radiation absorbed doses per injection activity for organs and tissues of adult patients following an intravenous bolus of Ga 68 dotatate are shown in Table 2. Estimated radiation effective doses per injection activity for adult and pediatric patients following an intravenous bolus of Ga 68 dotatate are shown in Table 3.

Gallium Ga 68 decays with a half-life of 68 minutes to stable zinc Zn 68:

  • 89% through positron emission with a mean energy of 836 keV followed by photonic annihilation radiations of 511 keV (178%),
  • 10% through orbital electron capture (X-ray or Auger emissions), and
  • 3% through 13 gamma transitions from 5 exited levels.

The effective radiation dose resulting from the administration of 150 MBq (4.05 mCi) [within the range of the recommended Ga 68 dotatate injection dose] to an adult weighing 75 kg, is about 3.15 mSv. For an administered activity of 150 MBq (4.05 mCi) the typical radiation dose to the critical organs, which are the urinary bladder wall, the spleen and the kidneys/adrenals, are about 18, 16 and 12 mGy, respectively. Because the spleen has one of the highest physiological uptakes, higher uptake and radiation dose to other organs or pathologic tissues may occur in patients with splenectomy.

1. Physical data
Gamma constant: 0.67 mrem/hr per mCi at 1 meter [1.8E-4 mSv/hr per MBq at 1 meter]
Specific Activity: 4.1E7 Ci/g [1.51E18 Bq/g] max
2. Shielding
Lead [Pb] Half Value Layer [HVL]: 6 mm (0.24 in)
Tenth Value Layer [TVL]: 17 mm (0.67 in)

Table 2 Estimated Radiation Absorbed Dose per Injection Activity in Selected Organs and Tissues of Adults after a Ga 68 Dotatate Injection Dose
Absorbed Dose per Injection Activity in Selected Organs and Tissues of Adults mGy/MBq  mGy/150 MBq 
Mean  SD 
 Adrenals  0.086 0.052  12.90
 Brain  0.010  0.002  1.50
 Breasts  0.010  0.002  1.50
 Gallbladder wall  0.016  0.002 2.40
 Lower large intestine wall  0.015  0.002  2.25
 Small intestine  0.025  0.004  3.75
 Stomach wall  0.013  0.002  1.95
 Upper large intestine wall  0.021  0.003  3.15
 Heart wall  0.018  0.003  2.70
 Kidneys  0.093  0.016  13.95
 Liver  0.050  0.015  7.50
 Lungs  0.006  0.001  0.90
 Muscle  0.012  0.002  1.80
 Ovaries  0.016  0.001  2.40
 Pancreas  0.015  0.002  2.25
 Red marrow  0.015  0.003  2.25
 Osteogenic cells  0.021  0.005  3.15
 Skin  0.010  0.002  1.50
 Spleen  0.109  0.058  16.35
 Testes  0.010  0.001  1.50
 Thymus  0.012  0.002  1.80
 Thyroid  0.011  0.002  1.65
 Urinary bladder wall  0.098  0.048  14.70
 Uterus  0.015  0.002  2.25
 Total body  0.014  0.002  2.10
 Effective dose per injection activity  mSy/MBq   mSy/150 MBq
 0.021 0.003  3.15 
Table 3 Estimated Radiation Effective Dose per Injection Activity after a Ga 68 Dotatate Injection Dose

Age

Effective Dose per Injection Activity (mSv/MBq)

Adult

0.021

15 years

0.025

10 years

0.040

5 years

0.064

1 year

0.13

Newborn

0.35

Table 3 indicates how effective dose per injection activity scales with body habitus in computational models of adult and pediatric patients.

Dosage Forms and Strengths

Netspot is supplied as a single-dose kit, containing two vials and an accessory cartridge for preparation of 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
  • Accessory cartridge: plastic column filled with silica to reduce the amount of Germanium 68 (Ge 68) potentially present in generator eluate [see Dosage and Administration (2.3) ].

Gallium 68 is obtained from an Eckert & Ziegler GalliaPharm Ge 68/Ga 68 generator and is not part of the kit.

After reconstitution with Ga68 and pH adjustment with Reaction Buffer, Vial 1 contains a sterile solution of Ga68 dotatate at a strength of 79.3 – 201.8 MBq/mL (2.1 – 5.45 mCi/mL).

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.

How Supplied/Storage and Handling

Netspot is supplied as a single-dose kit (NDC# 69488-001-40) for preparing a single-dose of gallium 68 (Ga 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)
  • One accessory cartridge (plastic column filled with 660 mg porous silica).

The radionuclide is not part of the kit. Before reconstitution and radiolabelling with Ga 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.

For prolonged storage, store Netspot in its original packaging at room temperature below 25°C (do not freeze). After reconstitution and radiolabeling [see Dosage and Administration (2.3) ] with activities of up to 1110 MBq (30 mCi), keep Ga 68 dotatate injection upright with an appropriate shielding to protect from radiation, at a temperature below 25 °C (do not freeze), and for a maximum of 4 hours. The storage of the radiolabelled product must comply with regulatory requirements for radioactive materials.

Patient Counseling 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 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 Ga 68 dotatate injection administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)] .

Manufactured by:

Gipharma S.r.l.

Strada Crescentino snc-1
3040 Saluggia (Vc), Italy

Distributed by:
Advanced Accelerator Applications USA, Inc., NY 10118

Kit Carton

Buffer Vial Label

Syringe Label

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