Ga-68-DOTATOC: Package Insert and Label Information (Page 2 of 2)

11.2 Physical Characteristics

Table 3 and Table 4 display the principal radiation emission data and physical decay of Ga 68.

Gallium-68 (Ga 68) decays with a half-life of 68 minutes to stable Zn 68:

  • 89% through positron emission with a mean energy of 836 keV followed by emission of two 511 keV annihilation photons (178%),
  • 10% through orbital electron capture (with associated X-ray or Auger emissions), and
  • 3% through 13 gamma transitions from 5 excited levels of the daughter Zn 68 nucleus. The most probable prompt gamma emission is a 1088 keV gamma with a 3.2% per decay probability.
Table 3: Principal Radiation Emission Data (>1%)
Radiation/Emission % Disintegration Mean Energy (MeV)
beta+ 88% 0.8360
beta+ 1.1% 0.3526
gamma 178% 0.5110
gamma 3% 1.0770
X-ray 2.8% 0.0086
X-ray 1.4% 0.0086
Table 4: Physical Decay Chart for Gallium Ga-68
Minutes Fraction Remaining
0 1.000
15 0.858
30 0.736
60 0.541
90 0.398
120 0.293
180 0.158
360 0.025

11.3 External Radiation

Gamma constant: 1.8 × 10-4 mSv/hr per MBq at 1 meter [0.67 mrem/hr per mCi at 1 meter] Table 5 displays the radiation attenuation by lead shielding of Ga 68.

Table 5: Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding
Shield Thickness(Pb) mm Coefficient of Attenuation
6 0.5
12 0.25
17 0.1
34 0.01
51 0.001

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Ga 68 DOTATOC binds to somatostatin receptors, with highest affinity (Ki = 2.5± 0.5 nanomolar) for subtype 2 receptors (sstr2). Ga 68 DOTATOC binds to cells that express somatostatin receptors including malignant neuroendocrine cells, which overexpress sstr2 receptors. Gallium 68 is a β+ emitting radionuclide with associated 511 keV annihilation photons that allow positron emission tomography (PET) imaging.

12.2 Pharmacodynamics

The relationship between Ga 68 DOTATOC plasma concentrations and successful imaging was not explored in clinical trials.

12.3 Pharmacokinetics

Distribution

Ga 68 DOTATOC distributes to all sstr2-expressing organs such as pituitary, thyroid, spleen, adrenals, kidney, pancreas, prostate, liver, and salivary glands. Uptake in the lung and lymph nodes are lower as compared to other sstr-2 expressing organs.

Elimination

Radiotracer elimination is exclusively via urine. Approximately 16% of the injected dose is excreted in urine in the first two to four hours post-injection.

14 CLINICAL STUDIES

The safety and efficacy of Ga-68 DOTATOC Injection were established in two single-center, open-label studies (Study A and Study B) in which 282 patients with known or suspected SSTR-positive NETs received a single dose of Ga-68 DOTATOC. A total of 238 of the 282 patients (84%) had a history of neoplasm at the time of Ga-68 DOTATOC imaging. Among the 282 patients, 59% were female and 95% white; the mean age was 54 years (range from 4 to 82 years).

The Ga-68 DOTATOC images were rated by two independent readers blinded to clinical information as either positive or negative for NET within each patient. The imaging results were compared to a composite reference consisting of histopathology and imaging (MR, CT, or In-111 pentetreotide imaging) acquired within 1 year of the Ga-68 DOTATOC imaging, as well as chromogranin A and pancreastatin levels. The proportion of patients positive for NET per composite reference who were identified as positive by the Ga-68 DOTATOC image was used to quantify positive percent agreement. The proportion of patients without NET per composite reference who were identified as negative by the Ga-68 DOTATOC image was used to quantify negative percent agreement.

Study A (NCT: 01619865) included 220 subjects with known or suspected SSTR positive tumors referred for diagnosis or evaluation of disease extension before or after treatment. A total of 178 of the 220 patients (81%) had a history of neoplasm at the time of Ga-68 DOTATOC imaging. In 177 of the 220 patients, sufficient data to establish NET status per composite reference was available for efficacy evaluation. Table 6 shows the performance of Ga-68 DOTATOC in the detection of NETs for Study A.

Table 6: Study A. Performance of Ga-68 DOTATOC in the detection of NET by reader
N = 177 NET status as identified by reader Reference
Positive Negative
N: number of patients, CI: confidence interval,
*
Percent reader agreement with reference;
Exact method
Reader 1 Positive 121 5
Negative 12 39
Agreement (%)* (95% CI) 91 (85, 95) 89 (75, 96)
Reader 2 Positive 120 6
Negative 13 38
Agreement (%)* (95% CI) 90 (84, 95) 86 (73, 95)

Study B (NCT: 01869725) included 62 patients with histologically positive NET or other SSTR positive tumor referred for evaluation of disease before or after treatment. In 59 of the 62 patients, sufficient data to establish NET status per composite reference was available for efficacy evaluation. The estimated positive and negative percent agreements were 92% and 75% for reader 1 and 90% and 75% for reader 2, respectively.

16 HOW SUPPLIED/STORAGE AND HANDLING

Ga 68 DOTATOC Injection is supplied in a multiple-dose, capped 30 mL glass vial containing 18.5 MBq/mL to 148 MBq/mL (0.5 mCi/mL to 4 mCi/mL) of Ga 68 DOTATOC at calibration time in approximately 14 mL of solution (NDC 24417-681-30).

Store Ga 68 DOTATOC Injection upright in a lead shielded container at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Receipt, transfer, handling, possession or use of this product is subject to the radioactive material regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreement States or Licensing States as appropriate. Store and dispose of Ga 68 DOTATOC Injection in accordance with the regulations and a general license, or its equivalent, of an Agreement State or a Licensing State.

17 PATIENT COUNSELING INFORMATION

Radiation Risk

Advise patients to drink water to ensure adequate hydration prior to their PET study and recommend they drink and urinate as often as possible during the first hours following the administration of Ga 68 DOTATOC Injection, in order to reduce radiation exposure [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

Lactation

Advise a lactating woman to interrupt breastfeeding and pump and discard breast milk for 8 hours after Ga 68 DOTATOC Injection administration in order to minimize radiation exposure to a breastfed infant [see Use in Specific Populations (8.2)].

Manufactured and Distributed by:
UIHC – P E T Imaging Center
0911Z JPP
200 Hawkins Drive
Iowa City, IA 52242

PRINCIPAL DISPLAY PANEL — 14 mL Vial Label

DOTATOC Ga 68 INJECTION

BATCH#
Diagnostic — For intravenous Use Only
Contains: 18.5 MBq/mL to 148 MBq/mL (0.5 mCi/mL to 4 mCi/mL) of no-carrier
added Ga-68 DOTATOC @ end of synthesis; 9 mg/mL of sodium chloride

Rx ONLY

Sterile, non-pyrogenic

Multiple-dose Vial

NDC# 24417-681-30

Manufactured by:
UIHC-PET Imaging Center
200 Hawkins Drive
Iowa City, IA 52242

TOTAL ACTIVITY: mCi
TOTAL VOLUME: mL
RADIOACTIVE CONCENTRATION: mCi/mL @ EOS TIME
EOS TIME:
EXPIRATION TIME:

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F–86°F);
Store upright in a lead shielded container. Expires 3 hours from end of synthesis.
See full prescribing information for dosage and administration information.

Do not use if cloudy or if contains particulate matter.CAUTION: RADIOACTIVE MATERIAL

PRINCIPAL DISPLAY PANEL -- 14 mL Vial Label
(click image for full-size original)
GA-68-DOTATOC edotreotide gallium ga-68 injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:24417-681
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
EDOTREOTIDE GALLIUM GA-68 (EDOTREOTIDE GALLIUM GA-68) EDOTREOTIDE GALLIUM GA-68 4 mCi in 1 mL
Inactive Ingredients
Ingredient Name Strength
ALCOHOL
sodium chloride
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:24417-681-30 14 mL in 1 VIAL, MULTI-DOSE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA210828 09/01/2019
Labeler — UIHC – P E T Imaging Center (063513265)

Revised: 12/2021 UIHC – P E T Imaging Center

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