Netspot

The NETSPOT kit is supplied as 2 vials

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 (⁶⁸Ge/⁶⁸Ga) generator
• IRE ELiT Galli Eo germanium-68/gallium-68 (⁶⁸Ge/⁶⁸Ga) generator

The⁶⁸Ge/⁶⁸Ga 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.

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

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.

• 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.
• 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 (size 21G to 23G; the amount of reaction buffer was determined in Table 1).
• Withdraw the syringe and the 0.2 micron sterile air venting filter.

• Set the Galli Eo generator for the elution according to manufacturer instructions. Connect a sterile needle (size 21G to 23G) 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 Galli Eo 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 Galli Eo 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
  .

k. Using a tong, move

to the heating hole of the dry bath, and leave the vial at 95°C (203°F), not to exceed 98°C (208°F), for at least 7 minutes (do not exceed 10 minutes heating) without agitation or stirring.

l. 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.

m. Assay the whole vial containing the gallium Ga 68 dotatate injection for total radioactivity concentration using a dose calibrator and record the result.

n. Perform the quality controls according to the recommended methods in order to check the compliance with the specifications

o. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.

p. Keep the vial containing the gallium Ga 68 dotatate injection upright in a radio-protective shield container at a temperature below 25°C (77°F) until use.

q. After addition of gallium-68 chloride to the reaction vial, use gallium Ga 68 dotatate injection within 4 hours. After radiolabeling, do not perform further dilutions.