Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment

Abstract

Pheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.

Animal and Cell Culture Models of PPGLs – Achievements and Limitations

“…Xenograft models based on the engraftment of the above-mentioned PPGL cell lines, parental and genetically engineered, have been generated. Expression of marker proteins such as luciferase (MTT-luc) [86], or fluorescent proteins (MPC-mCherry) have been successfully used to monitor tumor growth and drug behavior using imaging (reviewed by [87]. MTT-Sdhb -/cells were also used to allograft nude mice by Pang et al (2017) to study the effects of chemotherapy [88].…”

Preclinical magnetic resonance imaging and spectroscopy in the fields of radiological technology, medical physics, and radiology

“…Recently, several imaging modalities, including magnetic resonance imaging (MRI) [ 1 – 3 ], radiography, computed tomography (CT) [ 4 – 9 ], positron emission tomography (PET) [ 10 , 11 ], single-photon emission computed tomography (SPECT) [ 12 , 13 ], electron microscopy, autoradiography, optical imaging, and ultrasound (US) [ 14 – 17 ], have been applied in biomedical, genetic, toxicologic, cancer, cardiology, and pharmacological research worldwide. These are all noninvasive imaging modalities with proven clinical applications that have been extended to in vivo and ex vivo research specimens as small as mice, rats, and marmosets [ 9 , 18 , 19 ].…”