Society of Nuclear Medicine Procedure Guideline for
Somatostatin Receptor Scintigraphy with In-111
version 1.0, approved February 21, 2001
Authors: Helena R. Balon, MD (William Beaumont Hospital, Royal Oak, MI); Stanley J. Goldsmith, MD (New York Hos-
pital-Cornell Medical, New York, NY); Barry A. Siegel, MD (Mallinckrodt Institute of Radiology, St. Louis, MO);
Edward B.Silberstein, MD (University of Cincinnati Medical Center, Cincinnati, OH); Kevin J. Donohoe, MD (Beth Isreal
Deaconess Medical Center, Boston, MA); Eric P. Krenning, MD, PhD (University Hospital Dijkzigt, Rotterdam, Nether-
lands); and Otto Lang, MD (3rd Medical School, Charles University, Prague, Czech Republic ).
I. Purpose • differentiated thyroid carcinoma (papillary, fol-
licular, Hürthle cell)
The purpose of this guideline is to assist nuclear
• lymphoma (Hodgkin’s and non-Hodgkin’s)
medicine practitioners in recommending, perform-
ing, interpreting, and reporting the results of so-
• non-small cell lung carcinoma
matostatin receptor scintigraphy with In-111 pente-
• prostate carcinoma
• renal cell carcinoma
II. Background Information and Definitions • autoimmune diseases (e.g., rheumatoid arthritis,
Graves’disease, Graves’ ophthalmopathy)
Indium-111 pentetreotide is a [In-111 DTPA-D-Phe]
• bacterial pneumonia
conjugate of octreotide, a somatostatin analog that
binds to somatostatin receptors (predominantly so- • cerebrovascular accident
matostatin receptor subtypes sst2 and sst5). This oc- • fibrous dysplasia
tapeptide concentrates in neuroendrocrine and • granulomas (e.g., tuberculosis, sarcoid)
some non-neuroendrocrine tumors containing so- • radiation pneumonitis
matostatin receptors. Tumors that may be detected In addition to these tumors, normal organs, such
by somatostatin receptor scintigraphy with In-111 as the pituitary, thyroid, spleen, liver, and renal
pentetreotide include, but are not limited to: parenchyma also demonstrate avidity for this tracer.
• adrenal medullary tumors ( pheochromocytoma, The gallbladder, bowel, renal collecting systems,
neuroblastoma, ganglioneuroma) ureters and urinary bladder are seen as a result of
• GEP (gastroenteropancreatic) tumors, e.g., gas- clearance of In-111 pentetreotide.
trinoma, insulinoma, glucagonoma, VIPoma (va-
soactive intestinal polypeptide secreting tumor) III. Common Indications
and non-functioning GEP tumors
• carcinoid tumors A. Detection and localization of a variety of sus-
• medullary thyroid carcinoma pected neuroendocrine and some non-neuroen-
• melanoma docrine tumors and their metastases (see Inter-
• Merkel cell tumor of the skin pretation Criteria in section IV.H. below).
• paraganglioma B. Staging patients with neuroendocrine tumors.
• pituitary adenomas C. Determination of somatostatin-receptor status
• small-cell lung carcinoma (patients with somatostatin receptor-positive tu-
Other tumors and disease processes may also be mors may be more likely to respond to oc-
detected by In-111 pentetreotide scintigraphy and treotide therapy).
knowledge of the patient’s history is thus important. D. Follow-up of patients with known disease to
These disorders may include, but are not limited to: evaluate potential recurrence.
• astrocytomas E. Selection of patients with metastatic tumors for
• benign and malignant bone tumors peptide receptor radionuclide therapy (PRRT) and
• breast carcinoma prediction of the effect of PRRT, where available.
148 • SOMATOSTATIN RECEPTOR SCINTIGRAPHY
IV. Procedure The amount of pentetreotide injected is 10-20
mg; that dose is not expected to have a clinically
A. Patient Preparation
significant pharmacologic effect (see section
1. When appropriate, consideration should be
IV.C.1 above). In-111 pentetreotide is cleared
given to discontinuing octreotide therapy for rapidly from the blood (one-third of the injected
24 hr prior to In-111 pentetreotide administra- dose remains in the blood pool at 10 min, 1% at
tion, with monitoring the patient for signs of 20 hr postinjection). Excretion is almost entirely
withdrawal. See also Section K.2.a. via the kidneys (50% of the injected dose is re-
2. To reduce the radiation exposure, patients covered in the urine by 6 hr, 85% within 24 hr).
should be well hydrated prior to and for at Hepatobiliary excretion is only about 2% of the
least one day after injection. administered dose. It is not known whether In-
3. The use of laxatives should be considered, es- 111 pentetreotide is removed by dialysis.
pecially when the abdomen is the area of in- E. Image Acquisition
terest. A mild oral laxative (e.g., bisacodyl or 1. Patients should void prior to imaging.
lactulose) may be administered in the evening 2. Images are acquired at 4 and 24 hr or 24 and
prior to injection and in the evening following 48 hr post injection. The 48 hr images may be
injection. The need for bowel preparation needed when there is significant bowel activ-
should be assessed on an individual basis and ity at 24 hr, which may potentially obscure le-
laxatives should not be used in patients with sions. Four-hour images may be obtained to
active diarrhea. enable evaluation prior to appearance of ac-
B. Information Pertinent to Performing the Proce- tivity in the gut, but since tumor-to-back-
dure ground ratio is lower at 4 hr than at 24 and 48
A relevant history of the type of suspected or hr, some lesions may be missed at 4 hr.
known primary tumor, its hormonal activity, the 3. Planar images are acquired using a large-
results of other imaging studies (CT, MRI), labo- field-of-view gamma camera fitted with a
ratory results (tumor markers), history of recent medium-energy collimator. Symmetrical 20%
surgery, chemotherapy, radiation therapy, and energy windows are centered over both photo
octreotide therapy should be obtained. History peaks of In-111 (173 and 247 keV) and the data
of cholecystectomy should also be noted. from both windows are added. Planar local-
C. Precautions ized images of the head, chest, abdomen,
1. In patients suspected of having insulinoma, pelvis, and, if needed, the extremities can be
an intravenous infusion of glucose should be acquired for 10–15 min per image, using a 512
available because of the potential for inducing x 512 word or 256 x 256 word matrix. Occa-
severe hypoglycemia. sionally, images may be required in areas
2. In-111 pentetreotide should not be injected with low tracer activity. If this is the case, im-
into I.V. lines for, or together with solutions ages should be acquired in a suitable byte
for total parenteral nutrition. mode acquisition matrix. For whole-body im-
D. Radiopharmaceutical ages using a dual-head camera, it is suggested
In-111 pentetreotide is a [In-111 DTPA-D-Phe-] that anterior and posterior images are ac-
conjugate of octreotide, a long-acting somato- quired into 1024 x 512 word or 1024 x 256
statin analog (OctreoScan®). The recommended word matrix for a minimum of 30 min (head
administered activity is 222 MBq (6 mCi) in to upper femurs) and longer for the entire
adults and 5 MBq/kg (0.14 mCi/kg) in children. body (e.g., a speed of 3 cm/min has been sug-
Radiation Dosimetry for Adults*
Radiopharmaceutical Administered Activity Organ Receiving the Effective Dose
Largest Radiation Dose Equivalent
MBq mGy/MBq mSv/MBq
(mCi) (rad/mCi) (rem/mCi)
In-111 pentetreotide 222 spleen 0.117
(6) (2.46) (0.433)
* from OctreoScan® package insert, Mallinckrodt Medical, Inc. 1995.
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL JUNE 2002 • 149
gested) in a single pass. Since cervical lymph der, and occasionally the gallbladder. Intesti-
node metastases may be missed on the whole nal activity is usually not present at 4 hr, but
body images, additional planar localized im- may be present at 24 hr; 48 hr images may be
ages of the head and neck, including lateral necessary to clarify abdominal activity.
views, are suggested. 5. Islet cell tumors: peptide hormone-producing
SPECT imaging of the appropriate regions, endocrine tumors of the pancreas and GI tract
as indicated based upon the clinical history, and their metastases, including gastrinomas,
should be performed preferably with a multi- insulinomas, VIPomas (vasoactive intestinal
detector gamma camera. Early and delayed polypeptide-secreting tumors), glucagono-
SPECT may be helpful in distinguishing mas, as well as non-functioning islet cell tu-
bowel activity from pathological lesions. If mors may be imaged with In-111 pente-
only one SPECT acquisition is obtained, ac- treotide. The sensitivity for these lesions is
quisition at 24 hr is preferred because of 75–100% except for insulinoma, where it may
higher target-to-background ratio. be as low as 50–60%, due to the presence of
Although imaging systems may vary, an ex- different somatostatin receptor subtypes on
ample of potentially useful acquisition parame- this tumor.
ters for a multi-detector system are: 3° angular 6. Pheochromocytomas, neuroblastomas, and
sampling, 128 x 128 matrix, 360° rotation, 20–30 paragangliomas: the advantage of somato-
sec per stop. statin receptor scintigraphy with In-111 pen-
For more information see the Society of tetreotide is the ability to detect primary le-
Nuclear Medicine Procedure Guideline for General sions and metastases in unexpected
Imaging. (extraadrenal) sites not investigated by CT or
F. Interventions MRI. Tumors in the adrenal glands may be
None difficult to detect due to high renal activity;
G. Processing imaging with I-131 or I-123 meta-iodobenzyl-
See the Society of Nuclear Medicine Procedure guanidine (MIBG) may be preferable for tu-
Guideline for General Imaging. mor localization in the adrenal area. The sen-
In general, SPECT raw data are pre-filtered sitivity of In-111 pentetreotide for these
using an appropriate low-pass filter, the order tumors is over 85%.
and frequency according to local preferences and 7. Medullary thyroid carcinoma: the sensitivity
software manufacturer recommendations. The of In-111 pentetreotide scintigraphy may be
data is then reconstructed using a ramp filter and lower than for other tumors (65–70%). Com-
attenuation correction. Newer systems may in- parison with Tc-99m sulfur colloid scintigra-
clude iterative reconstruction algorithms, which phy for liver metastases or with I-123 scintig-
may eliminate some of the artifacts seen with fil- raphy for intrathyroidal tumors may increase
tered backprojection in areas adjacent to intense the rate of lesion detection, especially when
tracer activity. the uptake of In-111 pentetreotide in these or-
H. Interpretation Criteria gans is homogeneous.
1. When possible, images should be evaluated in 8. Carcinoid: the overall sensitivity of In-111
conjunction or fused with relevant anatomical pentetreotide scintigraphy is approximately
images (e.g., CT, MRI). 86–95%. For extrahepatic lesions, sensitivity
2. The optimal time interval to localize tumors is for lesions over 1 cm in diameter may exceed
at 24 hr postinjection or later. At 4 hr the back- 90%; however, hepatic lesions may be isoin-
ground activity may be high. Nevertheless, tense. SPECT imaging of the liver is recom-
early images may be important for compari- mended even if the planar images appear
son and evaluation of abdominal activity im- normal.
aged at 24 hr. 9. Intracranial tumors: meningiomas are rich in
3. Images are best viewed at the computer dis- somatostatin receptors and are therefore highly
play with individualized physician-directed detectable. In-111 pentetreotide scintigraphy
optimization of intensity and contrast. Three- may be used for postoperative follow-up of this
dimensional rendering of the SPECT data and tumor. Grade I and II astrocytomas are also so-
its review in cinematic display is encouraged. matostatin receptor-positive, grade III astrocy-
4. Knowledge of normal tissue accumulation of tomas may or may not be, while grade IV
In-111 pentetreotide is important for study in- (glioblastoma multiforme) is typically somato-
terpretation. This radiotracer is seen in the pi- statin receptor-negative. Localization of In-111
tuitary, thyroid, liver, spleen, kidneys, blad- pentetreotide in an astrocytoma also requires
150 • SOMATOSTATIN RECEPTOR SCINTIGRAPHY
that the blood-brain barrier be impaired. c. The tracer may accumulate at recent surgi-
10. Lung carcinoma: the sensitivity for primary cal and colostomy sites.
sites of disease is reported to be 80–100% for d. Accumulation of the tracer in normal struc-
small-cell lung cancer (SCLC), it may be lower tures (pituitary, thyroid, liver, spleen, kid-
for non-small cell lung cancer. neys, bowel, gallbladder, ureters, bladder,
I. Reporting stimulated adrenal glands) and in multiple
In addition to the general information to be pro- disorders (some listed in Section II) must
vided in each Nuclear Medicine report as recom- be kept in mind. Caution must be used to
mended in the Society of Nuclear Medicine avoid interpreting physiologic gallbladder
Guideline on General Imaging (section VI.D), it activity as hepatic metastasis.
is suggested that the report contain the following 2. Potential causes for a false-negative inter-
1. Indication: results of laboratory tests (e.g., a. Presence of unlabeled somatostatin, either as
neuroendrocrine tumor markers if applica- a result of octreotide therapy or due to pro-
ble), or results of other imaging studies as duction of somatostatin by the tumor itself
well as other relevant history (known tumor may lower tumor detectability, however,
and its type, recent radiation therapy, there are also literature reports of improved
chemotherapy). tumor-to-background ratio following pre-
2. Relevant medications: e.g., octreotide therapy treatment with non-radioactive octreotide.
and when stopped, chemotherapy, laxatives, b. Different somatostatin receptor subtypes
if given. have different affinities for the radioli-
3. Procedure description: timing of imaging rel- gand; variable tumor differentiation/re-
ative to radiopharmaceutical administration; ceptor expression also influences tumor
areas imaged; whether SPECT was performed detectability. This is a consideration, es-
and if so, its timing and body areas included. pecially with insulinomas and medullary
4. Study limitations: the referring physician may thyroid carcinomas.
be reminded that some tumors may lack so- c. Liver metastases of neuroendocrine tumors
matostatin receptors or the appropriate recep- may appear isointense because of a similar
tor subtypes and, therefore, may not be de- degree of tracer accumulation by the normal
tected. The differential diagnosis should liver. Correlation with anatomic imaging or
consider the many potential causes for a false- subtraction scintigraphy with sulfur colloid
positive study, as listed in section IV.K1. may be considered.
J. Quality Control
1. Prior to the administration of In-111 pente-
V. Issues Requiring Further Clarification
treotide, the labeling yield of the radiophar-
maceutical should be tested according to the A. Since In-111 pentetreotide elimination in pa-
manufacturer’s instructions. The product tients with impaired renal function has not been
should not be used if radiochemical purity is studied, possible dosage adjustment in these pa-
less than 90%. tients needs to be clarified.
2. The radiopharmaceutical should be used B. The role of In-111 pentetreotide scintigraphy in
within 6 hr of preparation. breast carcinoma, renal cell carcinoma,
3. In-111 pentetreotide should be inspected vi- Hodgkin’s and non-Hodgkin’s lymphoma and
sually prior to administration. Preparations other tumors (see section II.), as well as in the
containing particulate matter or color should evaluation and management of some granulo-
not be administered. matous and autoimmune processes (e.g. activity
K. Sources of Error of sarcoidosis, response of Graves’ ophthal-
1. Potential causes for a false-positive interpre- mopathy to steroids, etc) is yet to be determined.
tation: C. This procedure guideline only covers imaging
a. Accumulation of In-111 pentetreotide in with In-111 pentetreotide. Imaging with other so-
the nasal and pulmonary hilar areas can be matostatin analogs (e.g., Tc-99m depreotide) is not
seen with respiratory infections. a subject of this guideline.
b. Diffuse pulmonary or pleural accumula-
tion of In-111 pentetreotide can be ob-
VI. Concise Bibliography
served following radiation therapy to the
lung or bleomycin therapy. Gibril F, Reynolds JC, Chen CC, et al. Specificity of so-
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL JUNE 2002 • 151
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Med 1999;40:539-553 Revised March 1995
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and metastatic gastrinomas. Ann Intern Med Med 1995;25:251–261.
1996;125:26–34. Reisinger I, Bohuslavitzki KH, Brenner W, et al. So-
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Klutmann S, Bohuslavizki KH, Brenner W, et al. So-
matostatin receptor scintigraphy in postsurgical The Society of Nuclear Medicine has written and
follow-up examinations of meningioma. J Nucl Med approved guidelines to promote the cost-effective
1998;39:1913–1917. use of high quality nuclear medicine procedures.
Krenning EP, Kwekkeboom DJ, Bakker WH, et al. So- These generic recommendations cannot be applied
matostatin receptor scintigraphy with [In-111- to all patients in all practice settings. The guidelines
DTPA-d-Phe1] and [I-123-Tyr3]-octreotide: the Rot- should not be deemed inclusive of all proper proce-
terdam experience with more than 1000 patients. dures or exclusive of other procedures reasonably
Eur J Nucl Med 1993;20:716–731. directed to obtaining the same results. The spec-
Krenning EP, Kwekkeboom DJ, Pauwels S, et al. So- trum of patients seen in a specialized practice set-
matostatin receptor scintigraphy. Nucl Med Annual ting may be quite different than the spectrum of pa-
1995;1–50. tients seen in a more general practice setting. The
Kwekkeboom DJ, Krenning EP, Kho GS, et al. Somato- appropriateness of a procedure will depend in part
statin receptor imaging in patients with sarcoidosis. on the prevalence of disease in the patient popula-
Eur J Nucl Med 1998; 25:1284–1292. tion. In addition, the resources available to care for
Kwekkeboom DJ, Krenning EP: Radiolabeled somato- patients may vary greatly from one medical facility
statin analog scintigraphy in oncology and immune to another. For these reasons, guidelines cannot be
diseases: an overview. Eur J Radiol 1997; rigidly applied.
7:1103–1109. Advances in medicine occur at a rapid rate. The
Lebtahi R, Cadiot G, Sarda L, et al. Clinical impact of so- date of a guideline should always be considered in
matostatin receptor scintigraphy in the manage- determining its current applicability.