title: Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated thyroid carcinoma for determining the feasibility of peptide receptor radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for peptide receptor radionuclide therapy and evidence of chromogranin A level-positive neuroendocrine differentiation.
abstract: OBJECTIVE
  The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy.
  
  
  METHODS
  In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward.
  
  
  RESULTS
  Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin level was noted in one of the patients, and the other patient was lost to follow-up.
  
  
  CONCLUSIONS
  Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is observed in a relatively low fraction of patients that could favor the feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking into account that no treatment exists in this group, somatostatin receptor-targeted imaging can be an alternative diagnostic modality in the therapeutic decision making with peptide receptor radionuclide therapy and monitoring. The documentation of elevated serum chromogranin A level in 3 patients with intense tracer uptake could suggest a possible neuroendocrine differentiation in the affected tissues leading to the expression of chromogranin A along with SSTR-avid expression. This observation needs to be explored in future studies. No definite conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy in this group at present, and more prospective research is required in this area.
authors.affiliation: From the Radiation Medicine Centre (BARC), Tata Memorial Hospital Annexe, Parel, Bombay, India.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Jois
authors.forename: Ramesh
authors.initials: R
authors.lastname: Asopa
authors.forename: Sandip
authors.initials: S
authors.lastname: Basu
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D053379:Chromogranin A / Q000097:blood*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D015282:Octreotide / Q000031:analogs & derivatives*; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography; D018000:Receptors, Peptide / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
chemical_list: D053379:Chromogranin A; D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; D018000:Receptors, Peptide; D017481:Receptors, Somatostatin; C447941:lutetium Lu 177 dotatate; D015282:Octreotide