Trends in oncologic hybrid imaging

Abstract

Hybrid imaging plays a central role in the diagnosis and management of a wide range of malignancies at all stages. In this article, we review the most pertinent historical developments, emerging clinical applications of novel radiotracers and imaging technologies, and potential implications for training and practice. This includes an overview of novel tracers for prostate, breast, and neuroendocrine tumors, assessment of tumor heterogeneity, the concept of image-guided 'biologically relevant dosing', and theranostic applications. Recent technological advancements, including time-of-flight PET, PET/MRI, and 'one-minute whole-body PET', are also covered. Finally, we discuss how these rapidly evolving applications might affect current training curricula and how imaging-derived big data could be harnessed to the benefit of our patients.

Keywords: 11C–choline; 18F –Fluciclovine; 18F–Fluorodehydrotestosterone; 18F–Fluoroestradiol; 68Ga/ 177Lu -DOTA-TATE; 89Zr-trastuzumab; Oncologic hybrid molecular imaging; One-minute whole-body PET explorer; Prostate-specific membrane antigen; Time-of-flight positron emission tomography computed tomography.

Fig. 1

Timeline of Food and Drug Administration (FDA)-approvals of PET tracers and technical milestones, from 1972 to 2016. Abbreviations: NaF: Sodium fluoride, RbCl: Rubidium chloride, FDG: Fluorodeoxyglucose, PET: Positron Emission Tomography, CT: Computed Tomography, MRI: Magnetic Resonance Imaging, TOF: Time-of-Flight

Fig. 2

¹⁸F–FDG-PET/CTs in a patient with metastatic breast cancer before and after systemic therapy illustrating mixed treatment response. While an osseous cervical spine metastasis (green arrows) responded to treatment, several axillary lymph node metastases (red arrows) showed growth and increased FDG uptake. Mixed response to treatment is more commonly encountered in advanced, previously treated malignancies and hybrid imaging may help to prospectively identify patients in need for alternative treatment regimens

Fig. 3

a ⁸⁹Zr-Trastuzumab-PET/CT in a patient with HER2-negative primary breast cancer showing intense tracer uptake in a right supraclavicular lymph node metastasis. b Immunohistochemistry of the primary cancer proved HER2-negativity, while c biopsy and immunohistochemistry of the suspicious lymph node showed markedly HER2-positive metastatic disease. This patient responded to HER2-directed therapy. Adapted and reprinted with permission from Ulaner et al. J Nucl Med 2016;57:1523–1528

Fig. 4

In-vivo monitoring of drug-target-interaction with ¹⁸F–Fluoro-Estradiol (FES)-PET/CT in a patient with metastatic estrogen receptor-positive breast cancer being treated with an estrogen receptor-directed agent. The pre-therapy scan (top image) showed multiple chest wall metastases with avid tracer uptake. After initiation of the therapy (bottom image), tracer uptake resolved, while the size of the metastases did not change. It is important to recognize that these findings prove that the drug has hit its target but do not necessarily indicate treatment response. Retained tracer is seen in a central venous catheter on both studies

Fig. 5

¹⁸F–Fluorodeoxyglucose (FDG)- and ¹⁸F–Fluciclovine-PET/CTs in a patient with locally advanced invasive lobular breast cancer. A right axillary lymph node metastasis (blue arrows) showed mild FDG uptake (SUV: 2.1) but more marked Fluciclovine uptake (SUV 5.4)

Fig. 6

⁶⁸Ga-DOTA-TATE-PET/CTs in a patient with metastatic neuroendocrine tumor before (top row) and after (bottom row) radionuclide therapy with ¹⁷⁷Lu-DOTA-TATE. The pre-treatment diagnostic scan showed multiple avid liver metastases (arrows), implying that they would also bind the ¹⁷⁷Lu-labelled therapeutic ‘sister agent’, therefore predicting the treatment response that was ultimately demonstrated on the post-therapeutic PET/CT. Physiologic splenic tracer uptake is seen on both studies

Fig. 7

Schematic drawing of the basic principle of time-of-flight (TOF) PET. Annihilation events are marked as stars and the line of response as double-headed arrows. In conventional PET (non-TOF, yellow), the location of the annihilation event cannot be further located on the line of response and can only be deducted by reconstruction. In TOF PET (TOF, red), the time difference between the detection of both γ-rays is recorded, allowing for an estimation of the location of the annihilation event and resulting in a higher signal-to-noise ratio