NETSPOT, after radiolabeling with Ga 68, is indicated for
use with positron emission tomography (PET) for localization of somatostatin
receptor positive neuroendocrine tumors (NETs) in adult and pediatric patients.
DOSAGE AND ADMINISTRATION
After reconstitution and radiolabeling, handle the Ga 68
dotatate injection with appropriate safety measures to minimize radiation
exposure [see WARNINGS AND PRECAUTIONS]. 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.
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
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], 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]. Ensure
that the injected radioactivity is within ±10% of the recommended dose.
The NETSPOT kit is supplied as 2 vials and an accessory
cartridge [see Dosage Forms And Strengths] 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
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
- 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
Prepare Ga 68 dotatate for intravenous injection
according to the following aseptic procedure (Figure 1):
- Use suitable shielding to reduce radiation exposure.
- Wear waterproof gloves.
- 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.
- 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.
- 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
- 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.
- 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
- 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
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).
- 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.
- 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.
- 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.
- 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
- 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.
- Assay the whole vial containing the Ga 68 dotatate
injection for total radioactivity concentration using a dose calibrator and
record the result.
- Perform the quality controls according to the recommended
methods in order to check the compliance with the specifications [see Specifications and Quality Control].
- Prior to use, visually inspect the solution behind a
shielded screen for radioprotection purposes. Only use solutions that are clear
without visible particles.
- 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.
- After addition of Ga 68 chloride to the reaction vial,
use Ga 68 dotatate injection within 4 hours.
Figure 1 : Reconstitution procedure
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)
||Colorless and particulate free
||3.2 - 3.8
||Ga 68 dotatate ≥ 92% and Other Ga 68 species ≤ 5%
||Thin layer chromatography (ITLC, see details below)
Determine labeling efficiency of 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:
- 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
- Apply a drop of the Ga 68 dotatate injection on a pencil
line 1 cm from the bottom of the ITLC strip.
- 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).
- Scan the ITLC with a radiometric ITLC scanner
- 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%.
- 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
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.
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].
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
- 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.
- 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
- Shielding Lead [Pb] Â 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
|Lower large intestine wall
|Upper large intestine wall
|Urinary bladder wall
|Effective dose per injection activity
Table 3 : Estimated Radiation Effective Dose per Injection
Activity after a Ga 68 Dotatate Injection Dose
||Effective Dose per Injection Activity (mSv/MBq)
Table 3 indicates how effective dose per injection
activity scales with body habitus in computational models of adult and
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
- 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].
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).
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
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#
- 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
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] 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.
Manufactured by: Gipharma S.r.l. Strada Crescentino snc-1
3040 Saluggia (Vc), Italy. Distributed by: Advanced Accelerator Applications
USA, Inc., NY 10118. Revised: Apr 2018