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PEPTIDE RECEPTOR IMAGING Tumor cells , despite their seemingly uncontrolled metabolism and growth are in fact modulated by various endogenously peptides that interact with receptor on the tumor surface Somatostatin Tumor necrosis factor Angiogenesis factor Vasoactive intestinal peptide

Somatostatin It is a peptide hormone produced in the hypothalamus , pituitary gland , gastrointestinal tract and pancreas It acts as a neurotransmitter that inhibits peptide formation and secretion by neuroendocrine cells. Outside the central nervous system its hormone activities include inhibition of the physiologic and tumors release of growth hormone , insulin , glucagon, gastrin , serotonin and calcitonin It also has an antiproliferative effect on tumors.

Somatostatin Somatostatin receptors have been identified on many different cells and tumors of neuroendocrine origin Neuroendocrine cells are derived from the neural crest and have in common their ability to synthesize amines from precursors and produce peptide that act as hormone and neurotransmitter

Tumor with somatostatin receptors fall into three categories 1- Neuroendocrine Tumors (NETs) such as pituitary adenoma, gastrinoma ̗ insolinoma pheochromocytoma, medulary thyroid cancer and carcinoid 2- CNS tumors : Astrocytomas, menangioma and neuroblastoma 3- Other tumors, including lymphoma , breast lung (SCLC) and renal cell cancer

Neuroendocrine Tumors (NETs) A unique feature of NETs is their overexpression of somatostatin receptors on the tumor cells: imaging ( peptide receptor radionuclide therapy (PRRT) In the European consensus guidelines of ENETS from 2012, Octreotide Scan is an important part of the diagnostic work-up of patients with NETs. Localization of NETs primary tumors and unknown metastases in approximately 90% of patients.

Somatostatine Receptor Scintigraphy (SRS) in Other Tumors: Lymphoma can image many other human tumors expressing somatostatin receptors, including malignant lymphomas and thymomas. The sensitivity of SRS to image somatostatin receptor-positive tumors is very high The sensitivity of somatostatin receptor scintigraphy for Hodgkin’s lymphoma is 95%-100%, whereas for non-Hodgkin’s lymphoma it is around 80%.

OCTREOTIDE The first available somatostatin analog was octreotide Altering small parts of the synthetic peptides readily changes the binding profile to different receptors: Lanreotide Pasireotide Depreotide

Somatostatin Receptor Scintigraphy (SRS) Octreotide Scan(OctreoScan) Normal uptake occurs in the thyroid gland ,liver gallbladder , spleen , kidneys and bladder

Advantages of Somatostatine Receptor Imaging (SRI) SRI may detect resectable tumors that would be unrecognized with conventional imaging technique It may prevent surgery in patients with wide spread metastases Clarifying equivocal findings on CT or MRI It may direct the choice of therapy in patients with inoperable tumors It used to select patients for PRRT

Normal scintigraphic findings and artifacts of Octreoscan Visualization of thyroid , spleen , liver, kidneys , bladder , bowel and in a portion of patients , the pituitary gland False positive :Visualization of thyroid abnormalities , accessory spleen , recent CVA , activity at site of recent surgical incision , diffuse breast uptake in female , sarcoidosis and chest uptake after irradiation

Figure 1 illustrates normal, physiological distribution of 99mTc-EDDA/HYNIC-TOC in a human body. It can clearly be seen that the activity is accumulated mainly in the liver, spleen, kidneys and urinary bladder and, to a lesser extent, in the thyroid. The low background in the thoracic region is of particular importance for diagnostic evaluation of uptake by pulmonary tumours (Figs. 2, 3).                                                                                             

Fig. 4A, B. SPECT studies of the head (sagittal slices) Fig. 4A, B.  SPECT studies of the head (sagittal slices). A Normal uptake of 99mTc-EDDA/HYNIC-TOC in a pituitary gland. B Substantially enhanced uptake of the radiopharmaceutical in a growth hormone-secreting pituitary adenoma

Accuracy For more neuroendocrine tumors such as Gastrinoma , Pheochromocytoma Neuroblastoma and Carcinoid the sensitivity is very high (90%) Two exception are Insolinoma and Medullary thyroid carcinoma (only 50% sensitivity) The sensitivity for Lymphoma, Lung and Breast cancer is about 70%

Skeletal metastases of a pheochromocytoma Hurthle cell carcinoma remnant Bilateral carotid body paragangliomas Normal a neck lymphoma Sarcoidosis Skeletal metastases of a pheochromocytoma Gastroenteropancreatic tumor

On scintigraphy 24 hours after injection of 7 On scintigraphy 24 hours after injection of 7.4 GBq [177Lu-DOTA0,Tyr3]octreotate liver metastases were clearly visualized (arrows).

Gastrinoma

Carsinoid tumor Tc99m-Octreotide Tc99m-octreotate

False negative somatostatine scintigraphy 1- In small primary tumor (<1cm) 2- Tumors with low somatostatin receptors

False positive In areas of inflammation Occasionally in nonendocrine tumors.

Somatostatine Receptor Scintigraphy (SRS) in Lymphoma The sensitivity of SRS to image somatostatin receptor-positive tumors is very high The sensitivity of somatostatin receptor scintigraphy for Hodgkin’s lymphoma is 95%-100%, whereas for non-Hodgkin’s lymphoma it is around 80%.

Thorax of Patient 5. (A) 4-hr scintigram shows pericardial infiltration (arrows), bulky mediastinal disease (bold ar row) and a right supraclavicular lymph node (arrow-head). (B) Corresponding x-ray with mediastinal mass.

Nuclear Medicine in Lymphoma Gallium Scan was a cornerstone in functional imaging of lymphoma However : - Gallium may not be available physicians usually refuse to perform Gallium scan due to logistic problems Several days for imaging

Nuclear Medicine in Lymphoma FDG-PET is a promising functional imaging of lymphoma However : may not be available Its expensive

Nuclear Medicine in Lymphoma Somatostatin Receptor Imaging (Octreotide Scan) is also a useful functional imaging of lymphoma Available Reasonable cost (cost effective) Easy imaging in one day (less than 4 hours) Labeling with Tc99m: available and cheap

Nuclear Medicine in Lymphoma Somatostatin Receptor Imaging (Octreotide Scan+SPECT) : is useful and can be recommended : First: baseline before beginning the treatment In follow-up For assessment of response to therapy For assessment of relapse

Solitary Pulmonary Nodule (SPN) SPN radilogically defined as a single lesion that is <3cm in diameter , surround by lung parenchyma and without associated adenopathy or atelectasis Most SPNs are incidental findings at CXR or CT The incidence of malignancy in SPNs range from 10 to 70%

Lung: SPN The probability of malignancy is higher in heavy smokers with hemoptysis , higher age , larger nodule size or previous malignancy The differential diagnosis of an SPN include neoplastic ,inflammatory , vascular traumatic and congenital lesions and less frequently granulomas and sarcoidosis

SPN continue The main concern in a patient with SPN is to reach an accurate diagnosis of malignancy since an early detection enables a better prognosis

Tc99m-depreotide (Neotect) It is a somatostatin analog that has been approved specifically for detection of lung cancer in patients with pulmonary nodule (Approved by FDA for imaging of lung masses seen on CXR or CT) Many lung tumors express SS receptors to a greater extent than normal tissue To confirm pulmonary malignancy of a lung mass and for clinical staging. Because of the relatively high background activity and short half life of the tracer ,it is less suited for the detection of abdominal neuroendocrine tumor

Tc99m-Depreotide The accuracy of Depreotide in evaluation of indeterminate pulmonary nodules appears to be comparable to FDG PET (sensitivity 95% and specificity 85%)

   There has really been only one large published study with this radiopharmaceutical that looked at 114 indeterminate lung nodules the smallest ranged down to 0.8 centimeter, and that was a benign lesion. Imaging was done both with planar scintigraphy, as well as SPECT. All the lesions were confirmed by a biopsy. The sensitivity was 97% with false negative results in two primary adenocarcinomas, and one metastatic adenocarcinoma, while all of these lesions were under 2 centimeters. I think the smallest was 1.1 centimeter. Specificity has not been quite as good, however, with a specificity of only 73%. And the false positives were largely related to granulomas, which has been the bane of most of the nuclear medicine approaches, and one hamartoma. The explanation for that is not at all clear. Just a couple of quick examples from the published multicenter study. Here is a fairly good sized adenocarcinoma, which is easily seen on the SPECT image. TOP

V.R.Dabbagh; DSNMC; www.DSNMC.ir