OCTREOSCAN

OCTREOSCAN- indium in -111 pentetreotide
Curium US LLC

DESCRIPTION

Octreoscan^™ is a kit for the preparation of Indium In 111 Pentetreotide Injection, a radioactive diagnostic agent. It is a kit consisting of two components:

1) A 10-mL Octreoscan Reaction Vial which contains a lyophilized mixture of:
(i) 10 mcg pentetreotide [N-(diethylenetriamine-N,N,N′,N″-tetraacetic acid-N″-acetyl)-D-phenylalanyl-L-hemicystyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-L-hemicystyl-L-threoninol cyclic (2→7) disulfide], (also known as octreotide DTPA),
(ii) 2 mg gentisic acid [2, 5-dihydroxybenzoic acid],
(iii) 4.9 mg trisodium citrate, anhydrous,
(iv) 0.37 mg citric acid, anhydrous, and (v) 10 mg inositol.

Pentetreotide has the following structural formula:

Prior to lyophilization, sodium hydroxide or hydrochloric acid may have been added for pH adjustment. The vial contents are sterile and nonpyrogenic. No bacteriostatic preservative is present.

2) A 10-mL vial of Indium In 111 Chloride Solution, which contains: 1.1 mL or 111 MBq/mL (3 mCi/mL) indium In 111 chloride in 0.02N HCl at time of calibration. The vial also contains ferric chloride at a concentration of 3.5 mcg/mL (ferric ion, 1.2 mcg/mL). The vial contents are sterile and nonpyrogenic. No bacteriostatic preservative is present.

Indium In 111 Pentetreotide Injection is prepared by combining the two kit components (see INSTRUCTIONS FOR THE PREPARATION OF INDIUM In 111 PENTETREOTIDE INJECTION ). Indium In-111 reacts with the diethylenetriaminetetraacetic acid portion of the pentetreotide molecule to form indium In 111 pentetreotide. The pH of the resultant Indium In 111 Pentetreotide Injection is between 3.8 and 4.3. No bacteriostatic preservative is present.

The Indium In 111 Pentetreotide Injection is suitable for intravenous administration as is, or it may be diluted to a maximum volume of 3 mL with 0.9% Sodium Chloride Injection, USP, immediately before intravenous administration. In either case, the radiolabeling yield of Indium In 111 Pentetreotide Injection should be determined before administration to the patient. A method recommended for determining the radiolabeling yield is presented at the end of this package insert (see RECOMMENDED METHOD FOR DETERMINATION OF RADIOLABELING YIELD OF INDIUM In 111 PENTETREOTIDE INJECTION).

Physical Characteristics

Indium In-111 decays by electron capture to cadmium-111 (stable) and has a physical half-life of 2.805 days (67.32 hours) (see Table 2).1 The principal photons that are useful for detection and imaging are listed in Table 1.

Table 1. Principal Radiation Emission Data *

* Kocher, David C., “Radioactive Decay Data Tables,” DOE/TIC-11026, 115 (1981).
Radiation	Mean Percent Per Disintegration	Energy (keV)
Gamma-2	90.2	171.3
Gamma-3	94.0	245.4

The specific gamma ray constant for In-111 is 3.21 R/hr-mCi at 1 cm 1. The first half-value thickness of lead (Pb) for In-111 is 0.023 cm. Selected coefficients of attenuation are listed in Table 2 as a function of lead shield thickness. For example, the use of 0.834 cm of lead will attenuate the external radiation by a factor of about 1000.

Table 2. Radiation Attenuation by Lead Shielding

Shield Thickness (Pb) cm	Coefficient of Attenuation
0.023	0.5
0.203	0.1
0.513	0.01
0.834	0.001
1.12	0.0001

Table 3 lists fractions remaining at selected time intervals before and after calibration. This information may be used to correct for physical decay of the radionuclide.

Table 3. Physical Decay Chart: Indium In-111, Half-life 2.805 Days (67.32 hours)

* Calibration time
Hours	Fraction Remaining	Hours	Fraction Remaining
-72	2.100	0*	1.000
-60	1.854	3	0.970
-48	1.639	6	0.940
-36	1.448	12	0.885
-24	1.280	24	0.781
-12	1.131	36	0.690
-6	1.064	48	0.610

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1

From Radiopharmaceutical Internal Dosimetry Information Center, Oak Ridge Associated Universities, Oak Ridge, TN 37831-0117, February 1985.

CLINICAL PHARMACOLOGY

General

Pentetreotide is a DTPA conjugate of octreotide, which is a long-acting analog of the human hormone, somatostatin. Indium In 111 pentetreotide binds to somatostatin receptors on cell surfaces throughout the body. Within an hour of injection, most of the dose of indium In 111 pentetreotide distributes from plasma to extravascular body tissues and concentrates in tumors containing a high density of somatostatin receptors. After background clearance, visualization of somatostatin receptor-rich tissue is achieved. In addition to somatostatin receptor-rich tumors, the normal pituitary gland, thyroid gland, liver, spleen and urinary bladder also are visualized in most patients, as is the bowel, to a lesser extent. Excretion is almost exclusively via the kidneys.