NETSPOT (Page 2 of 5)

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.

​ Accidental extravasation may cause local irritation due to the acidic pH of the Ga 68 dotatate solution. In case of extravasation, the injection must be stopped, the site of injection must be changed and the affected area should be irrigated with sodium chloride solution.

Handle and dispose radioactive material in accordance with applicable regulations.

2.5 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 to 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 mm 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:

a) Pour ammonium acetate 1M: Methanol (1:1 V/V) solution to a depth of 3 mm to 4 mm in the developing tank, cover the tank, and allow it to equilibrate.

b) Apply a drop of the Ga 68 dotatate injection on a pencil line 1 cm from the bottom of an ITLC SG strip.

c) 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).

d) Scan the ITLC SG with a radiometric ITLC scanner.

e) 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%.

f) 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

2.6 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 minutes 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.

2.7 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 (5.3)].

2.8 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 mGy, 16 mGy 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 spleen disorders (e.g., splenectomy and splenosis) [see Risk for Image Misinterpretation (5.3)].

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	12.9
Brain	0.01	0.002	1.5
Breasts	0.01	0.002	1.5
Gallbladder wall	0.016	0.002	2.4
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	2.7
Kidneys	0.093	0.016	13.95
Liver	0.05	0.015	7.5
Lungs	0.006	0.001	0.9
Muscle	0.012	0.002	1.8
Ovaries	0.016	0.001	2.4
Pancreas	0.015	0.002	2.25
Red marrow	0.015	0.003	2.25
Osteogenic cells	0.021	0.005	3.15
Skin	0.01	0.002	1.5
Spleen	0.109	0.058	16.35
Testes	0.01	0.001	1.5
Thymus	0.012	0.002	1.8
Thyroid	0.011	0.002	1.65
Urinary bladder wall	0.098	0.048	14.7
Uterus	0.015	0.002	2.25
Total body	0.014	0.002	2.1
Effective dose per injection activity	mSv/MBq		mSv/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	0.04
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.