The Clinical Research Of Somatostatin Receptor Scintigraphy In Pheochromocytoma, Paraganglioma And Tumor-induced Osteomalacia

Project I[Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan in the evaluation of pheochromocytomas and paragangliomasObjective Pheochromocytoma and paraganglioma (pheochromocytoma and paraganglioma, PPGL) can secrete excess adrenaline and norepinephrine and induce hypertension. It is a rare type of secondary hypertension. Approximately 0.1% -1% of patients with sustained hypertension are reported to have a pheochromocytoma or paraganglioma. Because the tumour has secretion function, it requires special preparation before surgery. Therefore, correct preoperative diagnosis is essential to surgery. PPGL are known to overexpress somatostatin receptor(SSTR). The aim of the present study was to evaluate the diagnostic utility of [Tc-99m]-HYNIC-octreotide (99mTc-HYNIC-TOC) whole body scan in PPGL.Methods Between January 2013 and December 2015,1529 patients (842 women and 687 men; median age,59 y [range,8-88 y]) considered to have PPGL underwent 99mTc-HYNIC-TOC imaging. Diagnostic criteria was pathological diagnosis, clinical diagnostic standard and follow-up. All patients had biochemical results and conventional imaging findings. All patients were divided into two groups,and one was suspected PPGL group, the other was PPGL group after the surgery.338 patients also underwent 131I-MIBG imaging.Results In the suspected PPGL group,99mTc-HYNIC-TOC imaging show-ed detection rates of 63.7% in pheochromocytomas and 82.8%(P<0.01) in paragangliomas respectively of the patients with solitary lesion. The dete-ction rates of 99mTc-HYNIC-TOC imaging in patients with single lesion and multiple lesions were 70.8% and 94.1%(P<0.01) respectively. The sensi-tivity, specificity and accuracy of 99mTc-HYNIC-TOC imaging for diagnos-ing PPGL were 73.4%(95% confidence interval, CI,68.1-78.3%),97.9% (95%CI 96.9-98.6%) and 92.9%(95%CI 91.5-94.1%) respectively. The sensitivity, specificity and accuracy of 99mTc-HYNIC-TOC imaging for res-taging were 95.7%(95%CI,85.2-99.5%),100%(95%CI 84.2-100%) and 97.4%(95%CI 91.0-99.7%), respectively.In the suspected PPGL group,131I-MIBG imaging showed detection rates of 83.0% in pheochromocytomas and 70.4%(P<0.05) in paragangliomas respectively of the patients with solitary lesion. The sensitivity, specificity and accuracy of 131I-MIBG imaging for diagnosing PPGL were 79.1%(95% CI,72.7-84.6%),100%(95%CI 96.2-100%) and 87.9%(95%CI 83.9-91.2%), respectively. The sensitivity, specificity and accuracy of 131I-MIBG imaging for restaging were 66.7%(95%CI,43.0-85.4%),100%(95%CI 42.1-100%) and 74.1%(95%CI 53.7-88.9%), respectively.99mTc-HYNIC-TOC imaging and 131I-MIBG imaging were performed on 171 patients with solitary lesion.108(63.2%) were positive results,and 14 (8.2%) were false-negative results in both functional imaging.24 were 99mTc-HYNIC-TOC imaging-positive and 131I-MIBG imaging-negative,and 25 we-re 99mTc-HYNIC-TOC imaging-negative and 131I-MIBG imaging-positive. Of the 25 patients with multiple lesions,9 were positive results in both fun-ctional imaging,and 3 were 99mTc-HYNIC-TOC imaging-positive and 131I-MIBG imaging-negative,and 2 were 99mTc-HYNIC-TOC imaging-negative and 131I-MIBG imaging-positive. Of the 27 patients for restaging,21 were 99mTc-HYNIC-TOC imaging-positive, and of these,7 were 131I-MIBG imag-ing-negative.6 were true-negative results in both functional imaging.99mTc-HYNIC-TOC imaging detected more lesions than did 131I-MIBG imaging.Conclusions 131I-MIBG imaging was superior to 99mTc-HYNIC-TOC imaging in patients with pheochromocytomas, but 99mTc-HYNIC-TOC imaging was superior to 131I-MIBG imaging in patients with paragangliomas and metastatic PPGL.99mTc-HYNIC-TOC imaging provides complementary diagnostic information, and can help identify locally recurrent tumor,detect metastatic lesions and restaging accurately. It is of value for PPGL patients with negative 131I-MIBG findings or metastatic PPGL.Project Ⅱ68Ga-DOTATATE PET/CT in the localization of pheochromocytomas and paragangliomas compared with other functional imaging modalities and CTObjective Pheochromocytoma and paraganglioma (PPGL) overexpress somatostatin receptor (SSTR) and recent studies have already shown excellent results in the localization of neuroendocrine tumors(NET) using [(68Ga)-DOTA0,Tyr3]Octreotate ([68Ga]-DOTATATE) PET/CT. Our aim was to investigate the distribution of 68Ga-DOTATATE in normal mice and its imaging features in the SSTR-positive nude mice bearing pancreatic tumor(AR42J), and mainly assess the clinical utility of this functional imaging modality in PPGL compared to anatomical imaging with CT and other functional imaging modalities, including somatostatin receptor SPECT (SMSR SPECT) with 99mTc-HYNIC-octreotide(99mTc-HYNIC-TOC), scin-tigraphy with 131I-metaiodobenzylguanidine (MIBG), and 18F-FDG PET/CT.Methods Animal experiment:Mice were injected with 68Ga-DOTATATE through tail vein and killed respectively at 10,30,60,120 and 240 min after injection, and the radioactive counting of different organs were determined. MicroPET imaging in AR42J tumor-bearing mice was performed 10,30,60, 120,180 and 240 min after injection of 68Ga-DOTATATE(0.1mL/300-500μCi), and T/NT ratios were calculated.Clinical research:Between July 2014 to December 2015,20 patients (13 women and 7 men; median age,43 y [range,11-77 y]) considered to have PPGL underwent 68Ga-DOTATATE PET/CT. Diagnostic criteria was pathological diagnosis and clinical diagnostic standard.All the patients were found to have PPGL, and of these,15 were diagnosed by pathology including 3 after the surgery.All patients had biochemical results, other functional imaging, and conventional imaging findings. All patients underwent 68Ga-DOTATATE PET/CT, SMSR SPECT and CT, with 18 and 12 patients also receiving MIBG imaging and 18F-FDG PET/CT respectively on average within 1 m.Results Animal experiment:For 68Ga-DOTATATE,we observed favorable biodistribution profiles in mice:1) a specific uptake in SSTR-positive tissues; 2) a rapid clearance from all SSTR-negative tissues except kidney. The main route of excretion was via the kidneys. SSTR-positive nude mice bearing AR42J tumor was imaged clearly 30min after injection when the ratio of tumor to non-tumor was higher.Clinical research:Of the 20 patients with PPGL,19 were positive results in 68Ga-DOTATATE PET/CT,and 1 were false-negative result in all func-tional imaging,which was CT-positive. Sixteen were positive results in SMSR SPECT, and 13 of 18 were positive results in MIBG imaging, with 10 of 12 positive results in F-FDG PET/CT respectively. CT was positive in all cases. The per-patient detection rates for 68Ga-DOTATATE PET/CT, SMSR SPECT, MIBG imaging,18F-FDG PET/CT and CT were 95.0%(95% confidence interval, CI 75.1-99.9%),80.0%(95%CI 56.3-94.3%),72.2%(95% CI 46.5-90.3%),83.3%(95%CI 51.6-97.9%) and 100%(95%CI 76.2-100%), respectively. The lesions in 4 cases were first detected by 68Ga-DOTATATE PET/CT.Sixty-three lesions were assessed. Of those,19 lesions were in patients with only primary lesions and 44 lesions were in patients carrying metastatic lesions. On 68Ga-DOTATATE PET/CT,58 out of 63 lesions with a mean SUVmax of 14.7±13.7 were identified.68Ga-DOTATATE PET/CT missed one abdominal lesion and four lung lesions which were positive on CT and negative on SMSR SPECT and MIBG imaging. Three lesions were negative on 18F-FDG PET/CT except two lung lesions which didn’t undergo 18F-FDG PET/CT.Of 63 lesions,23 were positive in SMSR SPECT, and 13 of 61 were positive in MIBG imaging respectively. On 18F-FDG PET/CT,13 out of 22 lesions with a mean SUVmax of 8.9±9.3 were identified. Of 63 lesions,42 were positive in CT,and 21 lymph node and bone lesions were false negative results.The per-lesion detection rates for 68Ga-DOTATATE PET/CT, SMSR SPECT, MIBG imaging,18F-FDG PET/CT and CT were 92.1%(95%CI 82.4-97.4%),36.5%(95%CI 24.7-49.6%, p<0.01),21.3%(95%CI 11.9-33.7%, p<0.01),59.1%(95%CI 36.4-79.3%, p<0.05) and 66.7%(95%CI 53.7-78.0%, p<0.01),respectively. Of the 58 68Ga-DOTATATE PET/CT-positive lesions, 21 were negative in other functional imaging modalities. Significantly more lesions were identified on 68Ga-DOTATATE PET/CT compared with all other functional imaging modalities and with CT (two-sided p< 0.05 for each imaging modality compared with 68Ga-DOTATATE PET/CT).Conclusions This study clearly demonstrated the superiority of 68Ga-DOTATATE PET/CT in detection of PPGL lesions over SMSR SPECT, MIBG imaging, 18F-FDG PET/CT and CT, which is supported by previous findings. We expect that 68Ga-DOTATATE PET/CT will become the preferred functional imaging modality for PPGL in the near future.Project ⅢEffective detection of the tumors causing osteomalacia using [Tc-99m]-HYNIC-octreotide(99mTc-HYNIC-TOC) whole body scanPurpose:Tumor-induced osteomalacia (TIO) is an endocrine disorder caus-ed by tumors producing excessive fibroblast growth factor-23 (FGF-23).The causative tumors are generally small, slow-growing benign mesenchymal tu-mors. The only cure of the disease depends on resection of the tumors,which are extremely difficult to localize due to their small sizes and rare locations. Since these tumors are known to express somatostatin receptors, this resear-ch was undertaken to evaluate efficacy of [Tc-99m]-HYNIC-octreotide (99 mTc-HYNIC-TOC) whole body imaging in this clinical setting.Methods:Images of 99mTc-HYNIC-TOC scans and clinical chart from 183 patients with hypophosphatemia and clinically suspected TIO were retrosp-ectively reviewed. The scan findings were compared to the results of histo-pathological examinations and clinical follow-ups.Results:Among 183 patients,72 were confirmed to have TIO while 103 pa-tients were found to have other causes of hypophosphatemia. The possibility of TIO could not be either diagnosed or excluded in the remaining 8 patients. For analytical purposes, these 8 patients who could neither be diagnosed nor excluded as having TIO were regarded as having the disease, bringing the total of TIO patients to 80. The 99mTc-HYNIC-TOC scan identified 69 tu-mors in 80 patients with TIO, which rendered a sensitivity of 86.3%(69/80). 99mTc-HYNIC-TOC scintigraphy excluded 102 patients without TIO with a specificity of 99.1%(102/103). The overall accuracy of 99mTc-HYNIC-TOC whole body scan in the localization of tumors responsible for osteoma-lacia is 93.4%(171/183).Conclusions:Whole body 99mTc-HYNIC-TOC imaging is effective in the localization of occult tumors causing TIO.