Skip to Content

Netspot Dosage

Generic name: DOTATATE 40ug;
Dosage form: kit

Medically reviewed on October 11, 2018.

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).

NETSPOT may be radiolabeled with Ga 68 chloride eluate from the following generators:

  • Eckert & Ziegler GalliaPharm Germanium 68/Gallium 68 (Ge 68/Ga 68) generator
  • IRE ELiT Galli Eo Germanium 68/Gallium 68 (Ge 68/Ga 68) generator

After reconstitution with Ga 68 chloride eluate and buffer [see Dosage and Administration (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 Dosage and 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 [see Dosage Forms and Strengths (3)] which allows for direct preparation of 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 (Ge 68/Ga 68) generator
  • IRE ELiT Galli Eo Germanium 68/Gallium 68 (Ge 68/Ga 68) generator

The Ge 68/Ga 68 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.

Prepare Ga 68 dotatate for intravenous injection according to the following aseptic procedure:

  1. Use suitable shielding to reduce radiation exposure.
  2. Wear waterproof gloves.
  3. 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%.
  4. 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.
  5. Prepare syringes for elution and reconstitution steps per Table 1 below. Prior to piercing vial septums, flip-off cap 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 syringe

5 mL of 0.1 N sterile HCl supplied by the generator manufacturer

For elution of the generator

1 mL sterile 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

Soultions for use with IRE Galli Eo generator
5 mL sterile syringe

3.9 mL sterile water for injection

For preliminary dilution of Vial 1

1 mL sterile 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

  1. 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.
  2. Follow the generator specific reconstitution procedures below. Then continue with the incubation step h.

Reconstitution with Eckert & Ziegler GalliaPharm generator

  • Connect the male luer of the outlet line of the GalliaPharm generator to a sterile needle.
  • 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.
  • Elute the generator directly into the Vial 1 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.
  • 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 in Table 1).
  • Withdraw the syringe and the 0.22 micron sterile air venting filter.

Reconstitution with IRE Galli Eo generator

  • Set the generator for the elution according to manufacturer instructions. Connect a sterile needle to the outlet tube of the generator, turn the button by 90˚ to loading position then wait 10 seconds before turning the button back to the initial position.
  • Reconstitute Vial 1 with 3.9 mL of sterile water for injection as prepared in Table 1.
  • Add the 0.1 mL reaction buffer to Vial 1 as prepared in Table 1.
  • Connect Vial 1 to the outlet line of the generator by pushing the needle through the rubber septum.
  • Connect one end of the two male luer ends of a sterile extension line to the 0.2 micron sterile vent filter inserted into Vial 1.
  • Assemble a sterile needle on the second male luer end of the sterile extension line and connect it to a sterile evacuated vial (17 mL minimum volume) by pushing the needle through the rubber septum. The generator elution will start.
  • Wait for the elution to be completed (minimum 3 minutes, according to the generator manufacturer instructions for use).
  • At the end of the elution, first withdraw the needle from the evacuated vial in order to establish atmospheric pressure into Vial 1, then disconnect Vial 1 from the generator by removing the needle from the rubber septum and remove the 0.2 micron sterile vent filter from Vial 1.

Incubation

  1. 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.
  2. 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.
  3. Assay the whole vial containing the Ga 68 dotatate injection for total radioactivity concentration using a dose calibrator and record the result.
  4. Perform the quality controls according to the recommended methods in order to check the compliance with the specifications [see Dosage and Administration (2.5)] .
  5. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
  6. 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.
  7. After addition of Ga 68 chloride to the reaction vial, use Ga 68 dotatate injection within 4 hours.

Figure 1. Reconstitution Procedure for Eckert & Ziegler GalliaPharm Generator

Figure 1. Reconstitution Procedure for Eckert & Ziegler GalliaPharm Generator

Figure 2. Reconstitution Procedure for IRE Galli Eo Generator

Figure 2. Reconstitution Procedure for IRE Galli Eo Generator

2.4 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 2 behind a lead glass shield for radioprotection purposes.


Table 2 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 ≥ 95% and Other Ga 68 species ≤ 5%

Thin layer chromatography (ITLC, see details below)

Determine labeling efficiency of Ga 68 dotatate applying one of the following recommended methods:

Obtain the following materials:

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

ITLC methods 1 and 2 (longer development length)

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 95%.
  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

ITLC method 3 (shorter development length)
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 an ITLC SG strip.
  3. Place the ITLC SG strip in the developing tank and allow it to develop for a distance of 6 cm from the point of application (i.e. to 7 cm from the bottom of the ITLC strip).
  4. Scan the ITLC SG 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 95%
  6. The retention factor (Rf) specifications are as follows:
    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 3. Estimated radiation effective doses per injection activity for adult and pediatric patients following an intravenous bolus of Ga 68 dotatate are shown in Table 4.

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 3 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 4 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 4 indicates how effective dose per injection activity scales with body habitus in computational models of adult and pediatric patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Hide