Case Report

Uptake Difference by Somatostatin Receptors in a Patient with Neuroendocrine Tumor: 99mTc-Octreotide Uptake in the Lung without Uptake in Liver Lesions


  • Elahe Pirayesh
  • Mahasti Amoui
  • Majid Assadi

Received Date: 21.07.2013 Accepted Date: 23.11.2013 Mol Imaging Radionucl Ther 2015;24(3):128-131 PMID: 27529888

The diagnostic value of somatostatin receptor scintigraphy (SRS) in detecting tumors has been assessed in a number of studies. We present a 30-year-old female with a history of eight months cough and left shoulder pain. Radiologic evaluation showed pulmonary mass and hepatic lesions, which were pathologically diagnosed as neuroendocrine carcinoma. 99mTc-octreotide scan demonstrated that the pulmonary lesion was positive for somatostatin receptor (SSTR), while the liver metastases were SSTR negative. The present case highlights the significance of a differential uptake pattern by somatostatin receptors in SRS in patients with neuroendocrine tumors.

Keywords: Radionuclide imaging,neuroendocrine tumors,99mTc-octreotide,receptors,somatostatin


Somatostatin receptor scintigraphy (SRS) is a functional imaging modality that is used to evaluate neuroendocrine tumors (1). The diagnostic value of SRS in detecting tumors has been assessed in a number of studies (1). Its uptake has been shown in different cell lines such as lymphocytes, fibroblasts, and endothelium (2). Herein, we present a 30-year-old female with neuroendocrine tumor of the lung and liver, with pulmonary 99mTc-octreotide uptake on SRS.

Case Report

A 30-year-old female, who had been suffering from a non-productive cough for 8 months and left shoulder pain, was found to have a large mass in the left lung (Figure 1). Further evaluation by abdominal sonography and computed tomography (CT) scan revealed multiple hepatic lesions (Figure 2). A CT guided biopsy of the liver lesions was performed. The liver sections showed poorly cohesive nests of epithelial cells with plasmocytoid and signet ring morphology, and solitary infiltrating cells with vascular permeation in a non-cirrhotic liver parenchyma, suggesting metastatic undifferentiated carcinoma with signet ring feature.

The immunohistochemistry (IHC) results were positive for EMA, CK, Chromogranin, Ki67 (1%) indices, but were negative for TTF1, GCDFP15, Heppar, Ck7, and Ck20 indices. IHC findings were in favor of metastatic low-grade neuroendocrine carcinoma.

She was healthy with an unremarkable past medical history, and she was not on any medications. Scintigraphic imaging was done 15 minutes and 3 hours after IV injection of 740 MBq (20 m mCi) 99mTc-Edda-tricine-Hynic-Tyro-octreotide, and an increased radiotracer uptake in the lung mass was identified (Figure 3). On planar images, there was a suspicious photopenic area in the posterior view of the liver (Figure 4). A SPECT was done and revealed some photopenic regions in the liver, compatible with the hepatic masses on CT images (Figure 5).

Literature Review and Discussion

Molecular imaging alters the diagnosis and treatment of patients with neuroendocrine tumors. SSTR scintigraphy has become the method of choice for functional imaging of these tumors (3). SRS with [111In-DTPA0] octreotide has established its role in the diagnosis and staging of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (4). In addition, radiolabelled metaiodobenzylguanidine (MIBG) has been applied for many years to detect carcinoid tumors (5). Somatostatin analogues have been labelled with different positron-emitting isotopes, such as Gallium-68 (68Ga) and Copper-64 (64Cu) (6). Furthermore, other PET radiotracers such as 18F-dihydroxy-phenyl-alanine (18F-DOPA) and 11C-labelled 5-hydroxytryptophan (11C-5-HTP) were introduced with promising results in detecting GEP-NETs (7).

Somatostatin receptors are overexpressed at the cell membrane and peritumoral vessels of a large variety of NETs. Although, various SSTR subtypes are expressed in tumors, SSTR2 is the predominant one, and it provides the molecular basis for clinical application of SS analogues for diagnostic and therapeutic purposes (8). However, it is well known that tumors frequently acquire cellular heterogeneity (9). This is related to tumorigenesis that is not a static entity: the tumor initiates from a genetically normal cell and proliferates into billions of malignant cells, during which it accumulates many mutations (9). There is strong evidence for the co-existence of genetically divergent tumor cell clones within a variety of tumors, and it has gained attention especially regarding response to therapy (9). It could also be a potential factor for sampling error (10). An IHC investigation reported heterogeneity in SSTR subtype expression between primary vs. metastatic NETs, as well as among hepatic metastases (11). There is also evidence for heterogeneity of Ki67 index in metastatic NETs (11).

In endocrine tumors, the presence of SSTRs are associated with well differentiation, low grade tumor and good response to somatostatin analog (octreotide) treatment (12,13).

While most well-differentiated endocrine tumors and islet cell carcinomas are SSTR-positive, and therefore responsive to somatostatin analog therapy; the poorly differentiated endocrine tumors are generally SSTR-negative and hardly benefit from somatostatin analog therapy (12,13,14,15).

The present case shows an uptake difference by somatostatin receptors in somatostatin receptor scintigraphy of a NET in the lung and its liver metastases, which can be explained by tumor heterogeneity and a different pattern of SSTR expression. In addition, it highlights the importance of SPECT study in detecting photopenic regions. Nuclear physicians should also be aware that all metastases do not necessarily appear as hot lesions. Photopenic areas require special emphasis.

Informed Consent: It was taken, Concept: Elahe Pirayesh, Design: Elahe Pirayesh, Mahasti Amoui, Data Collection or Processing: Elahe Pirayesh, Mahasti Amoui, Analysis or Interpretation: Elahe Pirayesh, Mahasti Amoui, Literature Search: Majid Assadi, Writing: Majid Assadi, Peer-review: External and internal peer-reviewed, Conflict of Interest: No conflict of interest was declared by the authors, Financial Disclosure: The authors declared that this study received no financial support.

1.    Esfahani AF, Chavoshi M, Noorani MH, Saghari M, Eftekhari M, Beiki D, Fallahi B, Assadi M. Successful application of technetium-99m-labeled octreotide acetate scintigraphy in the detection of ectopic adrenocorticotropin-producing bronchial carcinoid lung tumor: a case report. J Med Case Rep 2010;4:323.
2.    Cascini GL, Cuccurullo V, Rambaldi PF, Mansi L. [Immunological imaging using tagged octreotide]. Minerva Endocrinol 2001;26:129-133.
3.    Hofman MS, Hicks RJ. Changing paradigms with molecular imaging of neuroendocrine tumors. Discov Med 2012;14:71-81.
4.    Teunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer 2011;18(Suppl 1):27-51.
5.    Wafelman AR, Hoefnagel CA, Maes RA, Beijnen JH. Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry. Eur J Nucl Med 1994;21:545-559.
6.    Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, Kovacs P, Von Guggenberg E, Bale R, Virgolini IJ. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007;48:508-518.
7.    Koopmans KP, Neels OC, Kema IP, Elsinga PH, Sluiter WJ, Vanghillewe K, Brouwers AH, Jager PL, de Vries EG. Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol 2008;26:1489-1495.
8.    Rufini V, Calcagni ML, Baum RP. Imaging of Neuroendocrine tumors. Semin Nucl Med 2006;36: 228-247.
9.    Nasir A, Stridsberg M, Strosberg J, Su PH, Livingston S, Malik HA, Kelley ST, Centeno BA, Coppola D, Malafa ME, Yeatman TJ, Kvols LK. Somatostatin receptor profiling in hepatic metastases from small intestinal and pancreatic neuroendocrine neoplasms: immunohistochemical approach with potential clinical utility. Cancer Control 2006;13:52-60.
10.    Diaz-Cano SJ. Tumor heterogeneity: mechanisms and bases for a reliable application of molecular marker design. Int J Mol Sci 2011;13:1951-2011.
11.    Yang Z, Tang LH, Klimstra DS. Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J surg Pathol 2011;35:853-860.
12.    Reubi JC, Kvols L, Krenning E, Lamberts SW. In vitro and in vivo detection of somatostatin receptors in human malignant tissues. Acta Oncol 1991;30:463-468.
13.    Kvols LK, Reubi JC, Horisberger U, Moertel CG, Rubin J, Charboneau JW. The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to octreotide. Yale J Biol Med 1992;65:505-518.
14.    Papotti M, Bongiovanni M, Volante M, Allia E, Landolfi S, Helboe L, Schindler M, Cole SL, Bussolati G. Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchows Arch 2002;440:461-475.
15.    Oda Y, Tanaka Y, Naruse T, Sasanabe R, Tsubamoto M, Funahashi H. Expression of somatostatin receptor and effects of somatostatin analog on pancreatic endocrine tumors. Surg Today 2002;32:690-694.