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previously visited CARCINOID TUMOR SEEN ON IN-111 OCTREOTIDE SCAN
Contributed by: Radiology Residency Program Faculty & Staff, Northeastern Ohio Universities College of Medicine-Canton Affiliated Hospitals, Ohio, USA.
Patient: 69 year old male
History: 69 y M with abdominal pain.
Images:[small]larger

Fig. 1: Anterior and postrior whole body images of In-111 Octreotide scan show faint focal increased activity in the midline of abdomen. Physiologic uptake is seen in liver, spleen, kidney and blaader.

Fig. 2: An ill-defined mass left side of the aorta.

Fig. 3: A calcified mesenteric mass anterior to the aorta.

Fig. 4: In111 Octreotide scan: Multiple uptake in liver and T4 secondary to met. This case we cannot locate primary carcinoid or neuroendocrine tumor.

Fig. 5: CT: Multiple liver met.

Fig. 6: CT: Multiple liver met.
Findings: As image legend
Discussion:

Chemistry and Pharmacology:

Somatostatin is a small peptide hormone of 14 amino acids produced in the hypothalamus and pancreas. It's hormonal actions include inhibition of the release of growth hormone, insulin, glucagon, and gastrin. Somatostatin receptors are integral membrane glycoproteins that are distributed in a variety of tissues throughout the body. Somatostatin receptors are found on many cells of neuroendocrine origin, such as the somatotroph cells of the anterior pituitary and the pancreatic islet cells. Cells not classically regarded as neuroendocrine, such as lymphocytes, may also have these receptors. Receptors have also been identified on many endocrine related tumors such as Apudomas. These neoplasms have the ability to synthesize amines and polypeptides by virtue of amino precursor uptake and decarboxylation activity. Types of Apudomas include: Pancreatic endocrine (islet cell) tumors (gastrinoma, insulinoma, glucagonoma, VIPoma), carcinoid tumors, small cell lung carcinomas, neuroblastomas, pheochromocytomas, paragangliomas, medullary thyroid carcinoma, and certain pituitary tumors. Other tumors can also have somatostatin receptors such as: Hodgkins and non-Hodgkins lymphoma, certain brain tumors- meningiomas and astrocytomas, breast cancer, Merkel cell tumors of the skin, and granulomatous disease (Sarcoid). Other granulomatous diseases such as tuberculosis, Wegener's granulomatosis, DeQuervain's thyroiditis, and aspergillosis have also been shown to contain somatostatin receptors in vivo [1].

Octreotide is a somatostatin analogue consisting of eight amino acids. Pentetreotide has been shown to bind to somatostatin receptors on both tumor and non-tumor sites throughout the body. The agent is longer acting than the native hormone in vivo because of resistance to enzyme attack (half-life of 2 to 3 hours as opposed to 2-3 minutes for the native hormone). The agent is labeled to 111In-DTPA. After internalization through the somatostatin receptor system the agent is degraded to the final radiolabeled metabolite 111In-DTPA-D-Phe in the lysosomes [8]. This metabolite is not capable of passing through the lysosomal or other cell membrane and will remain within the cell [8]. The agent is then translocated to the perinuclear area and into the nucleus [7].

Auger electrons emitted from the In-111 (although low energy [0.5-25keV] and short ranged) can produce cytotoxic effects due to their proximity to the nucleus [7]. Clinical trials have been performed evaluating the use of high doses of In-111-DTPA Octreotide (150-200 mCi) for possible therapeutic applications in treating neuroendocrine neoplasms [8]. Other agents such as the high-energy beta-emitter Y-90 may also hold promise for therapeutic actions when labeled to Octreotide [8].

Distribution

Within an hour after injection most of the In-111 pentetreotide distributes from the plasma to the extravascular body tissues and by 20 hours only 1% of the dose remains in the blood pool. Tissue uptake is either related to the receptor status of target tissues or to the elimination of the radioligand. The normal pituitary gland (faint uptake), thyroid (faint uptake), liver, gallbladder, spleen, kidneys, and urinary bladder are visualized in most patients, as is the bowel to a variable degree. Faint diffuse breast uptake can also be seen in about 15% of female patients [8]. Normal uptake in the thyroid and liver may serve to mask lesions in these locations, but the kidenys and the spleen are the hottest organs on images. The spleen is the critical organ (14.5 rads/ 6 mCi). Octreotide is excreted almost exclusively by the kidneys (via glomerular filtration) with 85-90% of the dose recovered in the urine in the first 24 hours [17]. Uptake in the kidneys is for the most part from reabsorption of the radiolabeled peptide in the proximal renal tubular cells via megalin receptors after glomerular filtration [27]. Renal uptake can be reduced by the use of succinylated gelatin and this can have important implications for therapeutic uses of somatostatin receptor agents [27]. Somatostatin receptors have also been demonstrated in human renal tubular cells and the vasa recta [8]. There is little hepatobiliary excretion (2-10%), but bowel activity may sometimes be visualized on delayed 24 hour images, and a bowel prep should be given prior to imaging. Patients should be well hydrated during the exam to enhance renal clearance. The use of this agent in patients with impaired renal function should be carefully considered. The sensitivity of In-111 Pentetreotide may be reduced in patients concurrently receiving therapeutic doses of octreotide acetate (Sandostatin) for control of symptoms from certain tumors, although this has not been identified in clinical trials. It is nonetheless recommended that octreotide therapy be withheld for at least 24 to 72 hours prior to the exam if possible [2,17]. Octreotide in therapeutic doses has also been shown to produce severe hypoglycemia in patients with insulinomas. Although the agent is not expected to exert clinically significant effects, as pentetreotide is an octreotid analog, it could potentially also produce hypoglycemia. Patients suspected of having an insulinoma should have an I.V. solution containing glucose administered before and during the administration of the radiopharmaceutical. Transient adverse effects to Octreotide occur in less than 1% of patients and include dizziness, fever, flushing, HA, and hypotension.

Non-pathologic accumulation of the tracer has been demonstrated in the nasal and hilar regions of patients with URI's, and in the lung following external radiation or bleomycin chemotherapy. Thyroid uptake in patients with Graves' disease is increased and may be related to the presence of activated lymphocytes. Orbital uptake can be seen in patients with Graves' ophthalmopathy. Joint uptake can be seen in patients with rheumatoid arthritis associated with active inflammation and may be related to the presence of somatostatin receptor containing inflammatory cells [1]. In sarcoid nodal and parenchymal lung uptake are frequently seen [8]. Other sites of tracer accumulation include accessory spleens, recent cerebral vascular accidents, and recent surgical incisions [8].

Indications

Imaging has been successful in most patients with neuroendocrine tumors [24], and in patients with lymphomas, granulomatous diseases, or diseases in which activated lymphocytes play a role (such as Grave's ophthalmopathy [3]). In-111 Pentetreotide scan results have been shown to be consistent with the final diagnosis in 86% of patients. Compared with carcinoids (96% detection) and gastrinomas, lower success rates were noted for localization of insulinomas, neuroblastomas, pituitary adenomas, and medullary thyroid carcinoma. Specificity was approximately 50%. Imaging resulted in a change in patient management in 30% of cases. The sensitivity for the detection of liver metastases in patients with gastroenteropancreatic neuroendocrine tumors has been reported to be as high as 92% [24]. Dedifferentiation of certain tumors (such as carcinoids, neuroblastoma, and medullary thyroid carcinoma) results in a loss of somatostatin receptors that can result in falsely negative exams [26]. Symptomatic patients with positive scans can be treated with Octreotide with a high likelihood of control of the hormonal hypersecretion by the tumor.

False positive exams have occurred in the nasal and pulmonary hilar regions of patients with URI's; at sites of locally irradiated lung; and at sites of recent surgery. Bleomycin has been associated with increased pulmonary activity.

Technique

10 ug of the agent is labeled to 3 mCi of In-111 (I-123 has also been used). The dose of In-111 should be increased to 6 mCi if SPECT imaging is to be performed. SPECT imaging may increase the sensitivity of the exam and give better anatomic delineation compared to planar views [8]. The agent must be used within 6 hours of preparation. Images are obtained at 4 hours (over the area of interest) and 24 hours (from the head to the mid-thigh level) following injection. The exam is positive in 80 to 90% of cases by 4 hours. Planar images are obtained with a double-head or large field of view gamma camera, equipped with medium-energy, parallel hole collimators. The pulse height analyzer windows are centered over both In-111 photopeaks (172 keV and 245 keV) with a window width of 20%. The acquisition parameters for planar images are 300,000 preset counts or 15 minute view of the head and neck and 500,000 counts or 15 minutes for the remainder of the body. Generally 5 to 10 minute images are required for the images. A whole body exam may be performed using a scan speed of 3 cm/min. Using higher scan speeds, such as 8 cm/min, will result in failure to recognize small lesions or lesions with a low density of somatostatin receptors [8]. For SPECT images with a triple headed camera the acquisition parameters are: 40 steps or 3 degrees each, 64 x 64 matrix, and at least 30 seconds per step (45 seconds for brain SPECT).  Delayed images at 48 hours may also be obtained if necessary- particularly if there is a large amount of bowel activity on 24 hour images (a laxative should also be used to help clear bowel activity) [8].


Carcinoid tumors may be found anywhere in the GI tract, however, the appendix is the most common location (75% of cases and almost invariably benign). The ileum is the most common location outside the appendix (90% of cases). For tumors not located in the appendix, metastases are observed in less than 2% of cases in which the tumor is less than 1 cm in size, but are detected in about 90% of cases once the lesion exceeds 2 cm. Serotonin hypersecretion by carcinoid which has metastasized to the liver produces the characteristic "carcinoid syndrome" which includes flushing, diarrhea, bronchoconstriction, and right sided valvular heart disease. It may also occur in patients with bronchial, ovarian, or retroperitoneal tumors.

Octreotide has an overall sensitivity of about 86% in the detection of carcinoid tumors (range 71-100%) .In one study, in a small number of patients (n=33), Octreotide accumulation was identified in sites which were previously unsuspected or not recognized with other imaging modalities in 23 of 33 patients and detected at least one lesion in 15% of patients in whom no abnormalities were found relying on conventional imaging alone [5]. Unfortunately, confirmation that these abnormalities represented tumor was obtained in only eight patients and confirmation was not necessarily made by histologic analysis. Small lesions (under 1 cm) are frequently not identified on Octreotide imaging .

References: http://www.auntminnie.com/index.asp?sec=ref&sub=ncm&pag=tum&itemid=53467#Carcinoid
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Case Number: 10588481Last Updated: 09-07-2007
Anatomy: Gastrointestinal (GI)   Pathology: Neoplasm
Modality: CT, Nuc MedAccess Level: Readable by all users

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