Theranostics in Pheochromocytomas /Paragangliomas: Pilot study in Chinese Population

Background: Pheochromocytomas and paragangliomas (PHEOs/PGLs) are rare tumors arising from chromaffin tissues in adrenal medulla and in extra-adrenal sites including sympathetic and parasympathetic paraganglia, respectively. The aim of this study was to evaluate SSTR based theranostics in PHEOs/PGLs, and compared with ¹³¹I-MIBG.

Methods: Thirty-eight consecutive patients with suspected or known PHEOs/PGLs were consecutively enrolled in this study. All patients underwent ⁶⁸Ga-DOTA-NOC PET/CT, whereas twenty patients also had ¹³¹I-MIBG SPECT/CT in a month. Per-patient and per-lesion analysis were performed. Final diagnosis was confirmed by histopathology and clinical follow-up. ⁶⁸Ga-SSA positive patients with metastatic/unresectable tumors were recruited to ¹⁷⁷Lu-DOTA-TATE therapy, whereas ¹³¹I-MIBG positive patients underwent MIBG therapy. Adverse events were evaluated, tumor response was assessed by quality of life, serum CGA level, catecholamine and metabolites changes, remission of clinical symptoms and signs including better hypertension control and pain relief, all patients had a clinical follow-up for 1 year.

Results: For patient-based analysis, 31 patients were positive while 7 patients were negative on ⁶⁸Ga-DOTA-NOC PET/CT. The overall sensitivity, specificity and accuracy of ⁶⁸Ga-DOTA-NOC were 87.9%, 60% and 84.2%, respectively. On a lesion-based analysis, there are totally 218 lesions confirmed by histopathology or imaging follow-up. 190 lesions were interpreted as positive while 28 were negative. The overall sensitivity, specificity and accuracy were 89.9%, 77.8% and 89.4%, respectively. Analysis of detection rate and SUVmax was performed in 209 confirmed lesions in 34 cases proved to be PHEOs or PGLs, 188 lesions (89.95%) were detected by ⁶⁸Ga-DOTA-NOC PET/CT, SUVmax was 14.69±16.12. 62 bone metastasis(62/64,96.9%) in 13 patients and 46 metastatic lymph nodule(46/46, 100%) in 13 patients showed high expression of SSTR, SUVmax was 15.92±14.42 and 23.14±19.84, respectively. ⁶⁸Ga-DOTA-NOC PET/CT showed higher sensitivity in the detection of lymphadenopathy, remote and visceral metastasis with 131I-MIBG SPECT/CT. No remarkable adverse events were observed in 10 patients after 177Lu-DOTA-TATE therapy, function related symptom and hypertension were significantly released associated with obvious reduction of catecholamine and serum CGA.

Conclusions: ⁶⁸Ga-DOTA-NOC PET/CT shows higher sensitivity in the detection of bone metastasis and lymphadenopathy in PHEOs/PGLs, which has great merits for staging and risk stratification of PHEOs/PGLs. PRRT has good response especially in symptom release and improvement of living quality, and is tolerable with no evident hematological events and renal toxicity. Furthermore, present study will pave the way for SSA based theranostics on PHEOs/PGLs. Keywords: Pheochromocytomas, Paragangliomas, ⁶⁸Ga-DOTA-NOC,¹³¹I-MIBG, Somatostatin Receptor Abbreviations: PHEO: Pheochromocytoma; PGL: Paraganglioma; MIBG: Metaiodobenzylguanidine; SSTR: Somatostatin Receptor; SUV: standard uptake value; NOC: [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI3-Octreotide; PRRT: peptide receptor radionuclide therapy