Indium In 111 Pentetreotide (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): OctreoScan.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Diagnostic aid, radioactive (neuroendocrine tumors)—

Indications

Accepted

Neuroendocrine tumors (diagnosis)—Indium In 111 pentetreotide is indicated for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors, mainly growth hormone–secreting pituitary tumors, endocrine pancreatic tumors, carcinoids, other neuroendocrine tumors with typical amine precursor uptake and decarboxylation (APUD) characteristics (e.g., paragangliomas, medullary thyroid carcinomas, some pheochromocytomas, and small cell lung carcinomas), neuroblastomas, brain tumors (e.g., meningiomas and glial tumors, especially astrocytomas), Merkel cell tumors, lymphomas, and certain breast carcinomas. {01} {02} {04} {06} {07} {08} {09} {11} {12} {13} {14} {17}
—A drawback of indium In 111 pentetreotide for the localization of pheochromocytomas in the adrenal gland is its relatively high accumulation in the kidneys; therefore, I 123 or I 131 iobenguane ( 123I- or 131I-mIBG) may be preferable for this use. However, indium In 111 pentetreotide and 123I- or 131I-mIBG appear to be similar and complementary, providing comparable information in many patients; each provides superior results in some patients. {12} {19}


Physical Properties

Nuclear data: {01}



Radionuclide
(half-life)
Mode of
decay
Principal
photon
emissions
(keV)
Mean number
of emissions/
disintegration
In 111
(2.83 days)
Electron
capture
Gamma
(171.3)
0.90

    Gamma
(245.4)
0.94


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Pentetreotide, a diethylenetriaminopentaacetic (DTPA) conjugate of octreotide (an analog of somatostatin), binds to somatostatin receptors on cell surfaces throughout the body. Tumors containing a high density of somatostatin receptors concentrate indium In 111-labeled pentetreotide. After clearance of blood activity, visualization of somatostatin receptor-positive tissue is achieved with scintigraphic imaging techniques. {01} {02} {04} {06} {12} {19}

Distribution:

Within one hour of intravenous administration, indium In 111 pentetreotide is distributed from plasma to extravascular tissues and localizes in tumors as a function of the density of somatostatin receptors. Also, it localizes in the normal pituitary gland, thyroid gland, liver, spleen, urinary bladder, and to a lesser extent, in the bowel. Hepatic and biliary accumulation is 2% of the administered activity 4 hours after injection. {01} {02} {03} {06} {12} {19}

Time to radioactivity visualization

Optimal diagnostic images (planar and SPECT)—24 hours. {03} {12}

Note: Early scintigraphic demonstration of carcinoid liver metastases has been observed at 30 minutes, of meningiomas at 2 hours, and of small cell lung carcinomas at 4 hours postinjection of indium In 111 pentetreotide. {09} {10} {11} {19}
Repeat scintigraphy may be indicated at 48 hours when the 24-hour scintigram shows accumulation of radioactivity in the abdomen, which can represent normal bowel elimination of the indium In 111 pentetreotide. {12} {19}


Radiation dosimetry:
{01}

Estimated absorbed radiation dose *
Organ
mGy/MBq
rad/mCi
Spleen
0.66
2.46
Kidneys
0.49
1.80
Bladder wall
0.27
1.01
Liver
0.11
0.41
Large intestine
(lower)
0.07
0.26
Adrenals
0.068
0.25
Thyroid
0.067
0.25
Uterus
0.057
0.21
Large intestine
(upper)
0.052
0.19
Stomach wall
0.052
0.19
Ovaries
0.044
0.16
Small intestine
0.043
0.16
Red marrow
0.031
0.12
Testes
0.026
0.097
Effective dose: 0.12 mSv/MBq (0.43 rem/mCi)
* For adults; intravenous injection. Includes correction for maximum 0.1% indium In 114m contaminant, at calibration. Assumes 4.8 hour voiding interval. {01} Data based on calculations by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center. {01}
 Data estimated according to International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals. {01}

Elimination:
    Primarily renal. Fifty percent of the administered activity is excreted within 6 hours of injection, 85% within the first 24 hours, and over 90% by 2 days. During the first 4 hours after injection, indium In 111 pentetreotide appears predominantly in intact form (peptide-bound radioactivity) in the urine. {01} {03} {06} {12}
    Less than 2% of the administered activity is found in the feces within 3 days after injection. {01}
    It is not known whether indium In 111 pentetreotide can be removed by dialysis. {01}


Precautions to Consider

Carcinogenicity

Long-term animal studies to evaluate carcinogenic potential of indium In 111 pentetreotide have not been performed. {01}

Mutagenicity

No evidence of mutagenicity was found in an in vitro mouse lymphoma forward mutation assay and an in vivo mouse micronucleus assay. {01}

Pregnancy/Reproduction

Pregnancy—
Indium In 111 administered as indium chloride crosses the placenta. Studies have not been done with indium In 111 pentetreotide in humans. {01} {19}

The possibility of pregnancy should be assessed in women of child-bearing potential. Clinical situations exist in which the benefit to the patient and fetus, based on information derived from radiopharmaceutical use, outweighs the risks from fetal exposure to radiation. In these situations, the physician should use discretion and reduce the radiopharmaceutical dose to the lowest possible amount.

Studies have not been done in animals.

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether indium In 111 pentetreotide is distributed into breast milk. {01} Because of the potential risk to the infant from radiation exposure, temporary discontinuation of nursing is recommended for a length of time that may be assessed by measuring the activity of breast milk and estimating the radiation exposure to the infant. {15} {19}

Pediatrics

There have been no specific studies evaluating the safety and efficacy of indium In 111 pentetreotide in pediatric patients. {01} When this radiopharmaceutical is used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation.


Geriatrics


Diagnostic studies performed to date using indium In 111 pentetreotide have not demonstrated geriatrics-specific problems that would limit its usefulness in the elderly. {08} {13}

Diagnostic interference
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medications
Bleomycin    (may cause local pulmonary accumulation of indium In 111 pentetreotide {12})


Octreotide acetate    (concurrent administration of indium In 111 pentetreotide to patients receiving therapeutic doses of octreotide acetate may decrease the accumulation of radioactivity in the tumor; octreotide withdrawal for at least 12 hours is recommended {01} {02} {19})


Total parenteral nutrition (TPN) solutions    (administration of indium In 111 pentetreotide in TPN admixtures or into TPN intravenous lines may cause the formation of a complex glycosyl octreotide conjugate {01})


Due to medical problems or conditions
Cold/influenza    (may cause accumulation of radioactivity in the nasal region and lung hili {12} {19})


Insulinomas    (administration of octreotide has produced severe hypoglycemia in patients with insulinomas; since pentetreotide is an analog of octreotide, an intravenous solution containing glucose should be administered before and during administration of indium In 111 pentetreotide to minimize the possibility of hypoglycemia {01} {12})


Irradiation of lung, external    (may cause local pulmonary accumulation of indium In 111 pentetreotide {12})


Surgery, recent    (possible accumulation of radioactivity at sites of recent surgery {12})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Renal function impairment    (excretion of indium In 111 pentetreotide may be decreased {01})


Sensitivity to the radiopharmaceutical preparation


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare (less than 1%)
    
Dizziness
    
fever
    
flushing of skin
    
headache
    
hypotension (dizziness or lightheadedness)
    
increased sweating
    
joint pain
    
nausea
    
unusual weakness{01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Localization at sites of tumor spread or growth

Tumor sites may be visualized by external imaging

Small amounts of radioactivity used in diagnosis; radiation received is relatively low and considered safe

Before having this test
»   Conditions affecting use, especially:
Sensitivity to the radiopharmaceutical preparation

Pregnancy—Indium In 111 as indium chloride crosses placenta; risk to fetus from radiation exposure as opposed to benefit derived from use should be considered





Breast-feeding—Not known if distributed into breast milk; temporary discontinuation of nursing recommended because of risk to infant from radiation exposure





Use in children—Risk of radiation exposure as opposed to benefit derived from use should be considered


Preparation for this test
Special preparatory instructions may be given; patient should inquire in advance

Adequate intake of fluids before and after administration of indium In 111 pentetreotide; voiding as often as possible for 24 hours after administration to promote urine flow and to minimize radiation to bladder

Possible administration of a laxative before imaging, to minimize imaging interference due to radioactivity localization in stool


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the appropriate Federal or State agency, if required, or, outside the U.S., the appropriate authority. {18} {19}

Adequate hydration of the patient is recommended before and after administration of indium In 111 pentetreotide to promote urinary flow and blood pool clearance. Also, urination is recommended as often as possible for 24 hours after examination to promote urine flow, thereby minimizing radiation to the bladder. {01} {19}

Laxative administration prior to initial or follow-up images may be considered to minimize radioactivity, which may interfere with image interpretation, in bowel, due to excretion of radiopharmaceutical into stool. {01} {12}

Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. {16}


Parenteral Dosage Forms

INDIUM In 111 PENTETREOTIDE INJECTION

Usual adult and adolescent administered activity
For diagnosis of neuroendocrine tumors
For planar imaging: Intravenous, 111 megabecquerels (3 millicuries). {01}
For SPECT imaging: Intravenous, 222 megabecquerels (6 millicuries). {01}


Usual pediatric administered activity
Safety and efficacy have not been established. {01}

Usual geriatric administered activity
See Usual adult and adolescent administered activity .

Strength(s) usually available
U.S.—


10 micrograms of pentetreotide (DTPA-octreotide), 2 mg of gentisic acid, 4.9 mg of trisodium citrate (anhydrous), 0.37 mg of citric acid (anhydrous), and 10 mg of inositol, per 10-mL reaction vial; and in a separate 10-mL vial, 111 megabecquerels (3 millicuries) per mL of indium In 111 chloride sterile solution (Rx) [OctreoScan{01}]

Canada—
Not commercially available.

Packaging and storage:
Before radiolabeling, store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. {01}

Note: After radiolabeling, injection should be stored at or below 25 °C (77 °F) and administered within 6 hours. {01}


Preparation of dosage form:
To prepare injection, the sterile, pyrogen-free indium In 111 chloride solution is combined with the contents of the reaction vial. See manufacturer's package insert for complete instructions. {01}

Immediately before injection, the indium In 111 pentetreotide solution may be diluted with 0.9% sodium chloride injection to a maximum volume of 3 mL. {01}

Stability:
Injection should be administered within 6 hours after radiolabeling. {01}

Note: Caution—Radioactive material.




Developed: 01/24/1995



References
  1. OctreoScan package insert (Mallinckrodt—US), 7/94.
  1. Lamberts SWJ, Krenning EP, Reubi J-C. The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 1991 Nov; 12(4): 450-81.
  1. Krenning EP, Bakker WH, Kooij PPM, Breeman WAP, et al. Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J Nucl Med 1992; 33: 652-8.
  1. Reubi JC, Waser B, van Hagen M, et al. In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas. Int J Cancer 1992; 50: 895-900.
  1. Bakker WH, Krenning EP, Reubi JC, et al. In vivo application of [In-111-DTPA-D-PHE 1]-octreotide for detection of somatostatin receptor-positive tumors in rats. Life Sci 1991; 49: 1593-1601.
  1. Fischman AJ, Babich JW, Strauss HW. A ticket to ride: peptide radiopharmaceuticals. J Nucl Med 1993; 34(12): 2253-63.
  1. Kwekkeboom DJ, Krenning EP, Bakker WH, et al. Somatostatin analogue scintigraphy in carcinoid tumors. Eur J Nucl Med 1993 Apr; 20(4): 283-92.
  1. Kwekkeboom DJ, van Urk H, Pauw BKH, et al. Octreotide scintigraphy for the detection of paragangliomas. J Nucl Med 1993 Jun; 34(6): 873-8.
  1. Maini CL, Tofani A, Sciuto R, et al. Somatostatin receptors in meningiomas: a scintigraphic study using 111In-DTPA-D-Phe-1-octreotide. Nucl Med Commun 1993; 14: 550-8.
  1. Dörr U, Räaath U, Sautter-Bihl M-L, et al. Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue. Eur J Nucl Med 1993 May; 20(5): 431-3.
  1. Maini CL, Tofani A, Venturo I, et al. Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA-octreotide: a preliminary study. Nucl Med Commun 1993; 14: 962-8.
  1. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [ 111In-DTPA-D-Phe 1]- and [ 123I-Tyr 3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993; 20(8): 716-31.
  1. van Eljck CHJ, Krenning EP, Bootsma A, et al. Somatostatin-receptor scintigraphy in primary breast cancer. Lancet 1994 Mar 12; 343: 640-3.
  1. O'Byrne KJ, Ennis JT, Chancy LJ, et al. Scintigraphic imaging of small-cell lung cancer with In111-pentetreotide, a radiolabelled somatostatin analogue. Br J Cancer 1994; 69: 762–6.
  1. USP Radiopharmaceuticals Advisory Panel meeting 1/88.
  1. Reviewers' responses to Ballot of 5/11/94.
  1. van Hagen PM, Krenning EP, Reubi JC, et al. Somatostatin analogue scintigraphy of malignant lymphomas. Br J Haematol 1993; 83: 75-9.
  1. Standard statement per recommendation of the USP Radiopharmaceuticals Advisory Panel.
  1. Reviewers' responses to monograph draft of 10/06/94.
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