How to interpret and report ⁶⁸Ga-DOTA-TATE PET/CT Standard Uptake Value (SUV) measurement? Pearls and pitfalls

Introduction: The purpose of this educational exhibit is to shed light on clinical interpretation of the measured SUV in 68Ga-DOTA-TATE PET/CT imaging. As of June 1st 2016, 68Ga-DOTA-TATE PET/CT is approved by the FDA as the imaging standard of reference for management of the well-differentiated neuroendocrine tumors (NETs), providing greater accuracy in disease detection and characterization when compared with conventional imaging modalities. Qualitative evaluation of images plays a pivotal role in diagnosis and management of these patients, as reflected on SSTR-RADS Version 1.0 (Reporting System for SSTR PET). However, the clinical application of the conventional semi-quantitative measure (SUV) is controversial. The rationale for 68Ga-DOTA-TATE PET/CT is based on higher expression of somatostatin receptors (SSTRs) in NETs comparing to the other cells. Binding of radio-ligand (rL) to SSTR and subsequent internalization of the rL-SSTR complex result in accumulation of tracer within the cells. The measured SUV is the result of these complex interactions during the time between the injection of the tracer and imaging; the measured activity is the function of SSTR density (SSTR expression level per cell and concentration of the viable NET cells) as well as the other contributing factors including rL-SSTR binding potential, rates of internalization of rL-SSTR, and perfusion rate of the tracer. The variable rate of internalization and dissociation between receptor expression and internalization, in addition to the other confounding factors, significantly affect the measured SUV. How to convey the meaning of measured SUV to clinicians? We will address this by reviewing the literature systematically; the following concepts will be discussed: 1. Principles of SSTR expression and biology in NETs: a. modeling of receptor binding and internalization. b. receptor expression regulation. c. dynamic interaction of Somatostatin Analogs (SSA) with SSTR. 2. Basics of 68Ga-SSA PET/CT imaging and SUV measurement, including the effect of competitive inhibition in patients undergoing somatostatin analog therapy. 3. Beyond the basics: Anatomy of 68Ga-SSA SUV: a. What is the net uptake rate (Ki) and does SUV properly resemble receptor expression and different receptor density levels? b. How to model 68Ga-SSA kinetic? c. What is the impact of tumor burden on SUV? d. Can we use SUV for treatment planning? e. What is the prognostic value of pre-treatment SUV and total tumor tracer uptake quantification? f. Can we use SUV to evaluate treatment response, as we do with 18F-FDG PET/CT SUV? 4. Take Home message: What clinicians should know about SUV measurement when interpret and report 68Ga-DOTA-TATE PET/CT.