Nuclear medicine imaging and treatment in pheochromocytoma, paraganglioma, and role of the new tracer 11C-hydroxy ephedrine in diabetes mellitus

Abstract: Carbon-11 hydroxy ephedrine (11C-HED) is a norepinephrine analog which binds to the norepinephrine receptor present in adrenal medulla, lung, liver and pancreas. 11C-HED-positron emission tomography with concomitant computed tomography (PET/CT) can image these organs. Pheochromocytoma (PCC) and Paraganglioma (PGL) are rare, chromaffin cell tumors, which may mimic other diseases and can be difficult to diagnose because of vague and uncharacteristic symptoms. The diagnosis of PCC/PGL is reached either by detection of excessive catecholamines or metanephrines in plasma or urine, or may be detected incidentally on computed tomography (CT)/magnetic resonance imaging (MRI) as an “incidentaloma”. Also, these tumors are most heritable endocrine neoplasms, and can metastasize in up to 20% of patients. Better post-operative surveillance, re-staging on evidence of recurrent disease, biochemical recurrence and therapy monitoring is needed in these patients to improve care. Also, in inoperable cases and metastatic disease of neuroendocrine tumors (NETs), peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising nuclear medicine therapy. Recent studies have shown a connection between sympathetic nervous system and diabetes mellitus both type 1(T1D) and type 2(T2D), which are a global health burden. However, underlying pathophysiology of both types are not well understood.  The aims of this thesis was, in Paper I to establish the role of 11C-HED PET/CT in complex clinical scenarios to diagnose or rule out primary tumors of PCC/PGL (n=102). In Paper II, to determine the outcome of treatment with 177Lu-DOTATATE in PCC/PGL (n=22), in Paper III to assess the additional clinical benefit of 11C-HED PET/CT in in patients with metastatic PCC/PGL in comparison to morphological imaging, CT/MRI and other available imaging (n=74), in Paper IV to establish 11C-HED PET/CT for non-invasive imaging of the pancreatic sympathetic innervation in individuals with T2D (n=25) and non-diabetics (n=64).We demonstrate that 11C-HED PET/CT is a valuable diagnostic tool to diagnose or rule out pheochromocytoma and paraganglioma. Also, it is excellent in surveilling metastatic disease post-surgery, monitoring therapy with parameters such as standardized uptake value (SUV) and total catecholamine transporter tumor volume (TCTTV) and provides additional benefit in complex clinical scenarios. Upon treatment with 177Lu-DOTATATE patients with PCC/PGL had a favorable outcome with low toxicity. There was focal accumulation of 11C-HED in the sympathetic innervation of the pancreas and CT helped in delineation and further segmentation. In conclusion, we showed the role of new radiotracer 11C-HED and theragnostic option, PRRT with 177Lu-DOTATATE successfully better nuclear medicine diagnosis and therapy in pheochromocytoma, paraganglioma and diabetes mellitus.