A Practical Guide for the Production and PET/CT Imaging of ⁶⁸Ga-DOTATATE for Neuroendocrine Tumors in Daily Clinical Practice

This protocol describes the synthesis and quality control of gallium DOTATATE and the subsequent acquisition of a gallium DOTATATE PET/CT scan. The main advantage of this technique is that it provides high quality gallium DOTATATE within a timeframe suitable for working with an isotope of a short half-life. Demonstrating the procedures will be Else von Bele and Marine Decker, nuclear medicine technologists at our department.

At least two hours before patient administration place the gallium-68 labeling kit on the labeling module according to the manufacturer's specifications, and place the materials in the correct position. Attach the solutions provided in the gallium-68 labeling kit to the manifolds. And attach the sterile vial with the non-vented filter to the output of the labeling module.

Place the vial in a lead shield sufficient for positron emitters. And attach the output of the 68-gallium generator to the input of the labeling module. Dissolve 50 micrograms of peptide analog into 1.5 milliliters of 1.5 molar HEPES buffer solution provided in the kit, and transfer the peptide to the reaction vial.

Close the lead shielding around the labeling module and start the production of the gallium-68 DOTATATE via the tablet computer attached to the labeling module. When the synthesis is finished, remove the needles with filters from the glass vial and close the lead shield around the vial. Place the vial in a dose calibrator to measure the activity of gallium-68 DOTATATE and note the activity reference time.

Then in a sterile environment, remove 0.5 milliliters of the labeled peptide from the vial for quality control, and prepare syringes for the patient administration. To confirm the quality of the synthesized peptide before the administration, visually inspect the final gallium-68 DOTATATE product to ensure that it is a colorless liquid without any particles. Use a pH indicator strip to measure the pH of the solution.

The pH should lie between 6.5 and 7.5. Next, to measure the gallium-68 colloids add 20 microliters of the labeled peptide to 500 microliters of water. And homogenize the dilution with careful shaking of the vial.

Next add five microliters of the dilution about 1.5 centimeters from the bottom of a seven-centimeter long, one-centimeter wide strip of instant thin layer chromatography silica gel glass fiber paper. And place the paper in a tube containing two milliliters of a 50-50 methanol to one molar ammonium acetate solution taking care that the peptide does not come into contact with the solution. Close the tube to prevent evaporation and wait several minutes until the solvent has traveled at least five centimeters above where the peptide was applied.

Next, cut the paper in half and place the bottom and upper halves in separate tubes. Then place the tubes in a well counter and determine the number of counts in each vial in the 400 to 600 electron volt energy window for 30 seconds to determine the colloid percentage. To determine the 68-gallium ions dilute 20 microliters of gallium-68 DOTATATE in one milliliter of five millimolar EDTA.

Then dilute 10 microliters of the peptide EDTA solution in one milliliter of sterile water, and place the solution in a well counter to determine the number of counts in the 400 to 600 electron volt energy window for 30 seconds. Slowly flush a C-18 cartridge with one milliliter of 100%ethanol followed by one milliliter of sterile water. Flush the diluted sample through the C-18 cartridge into the collection tube.

Rinse the sample tube with one milliliter of water and flush the wash through the column into the collection tube. Place the collecting tube, the empty sample tube, and the syringe in a well counter and determine the number of counts in each material in the 400 to 600 electron volt energy window for 30 seconds to estimate the ion percentage. The radiopharmaceutical purity can then be determined by calculating the total amount of gallium-68 DOTATATE according to the formula.

If the radiopharmaceutical purity is at least 91%obtain a short medical history of the patient after check-in taking care to inquire about the date of the last somatostatin analog administration. This is not a contraindication for gallium-68 DOTATATE imaging, but should be noted. When the patient is ready, place an intravenous cannula in the arm, and flush the catheter with saline to verify placement of the cannula.

45 minutes prior to the PET/CT imaging inject 100 megabecquerels of gallium-68 into the cannula. Place the patient with the arms above their head on the PET/CT scanner and instruct the patient to remain still throughout the exam. When the patient is in position acquire a survey image and select the scan area from the pituitary gland to the mid thigh.

Perform a low dose CT scan with 40 milliamps, 140 electron volts, and five millimolar slices for attenuation correction and anatomical correlation. Then starting at the head of the patient perform a PET scan with 150 seconds per bed position. Here a representative gallium-68 DOTATATE PET/CT scan without evidence of disease is shown.

The physiological uptake can be observed in the liver and the spleen. Gallium-68 DOTATATE is excreted by the kidneys and is therefore visible in the urinary track. Here, images from a patient with a primary tumor in the pancreas are shown.

This patient was administered a lower dose of gallium-68 DOTATATE due to a delay in the production of the labeled peptide, which led to less activity being present in the patient and two more noisy images. This can be seen in the liver, which is indicated by the red arrow. Here, an image with motion artifact can be observed, which is indicated by the red arrow.

Gallium-68 has a short half-life of 68 minutes, therefore, timing is critical in this protocol. This protocol makes use of the positron-emitting isotope gallium-68, therefore adequate protective measures should be taken to keep the radiation exposure of personnel as low as possible.