Digital high sensitivity I-124 PET/CT improves the detectability of thyroid cancer metastases

Introduction: Increasing or persistent thyroglobulin (TG) levels in differentiated thyroid cancer (DTC) patients after total thyroidectomy and radioiodine therapy (RIT) are linked with metastatic disease and poor outcome. Radioiodine uptake imaging represents the standard diagnostic instrument for identification of metastases. DTC patients may benefit from early treatment of metastases exploiting a potentially improved detection by a novel digital (SiPM-based) and high time resolution I-124 PET/CT. The aim of this study is to quantify the minimal detectable activity (MDA) for a digital high time resolution versus a conventional PET/CT system and to assess the possible impact on RIT using phantom and patient data.

Methods: Phantom measurements were performed under challenging, but clinically realistic conditions (derived from almost 200 DTC metastases): an abdominal phantom containing small spheres with diameters ranging from 3.7 to 9.7 mm, activity concentrations (ACs) from 0.25 to 25 kBq/mL and a low signal-to-background ratio of 20:1. PET data were acquired on a digital Siemens Biograph Vision (SiPM-based, 3.2 mm crystals, 214 ps TOF) and a conventional Siemens Biograph mCT (PMT-based, 4.0 mm crystals, 540 ps TOF) using a standard clinical acquisition protocol (4-min emission time per bed position, TOF+PSF image reconstruction). The contrast-to-noise ratio (CNR) was evaluated as a function of the AC. The MDA was defined as the AC at which a CNR of 8 indicated visibility (Rose criterion). For each sphere, the MDA was determined using a cubic spline regression analysis. Data sets of 6 DTC patients with increasing TG levels after total thyroidectomy and after RIT were included. PET/CT data were acquired approximately 1 d after oral administration of 37 MBq I-124. All patients were examined on both scanners within 2 h (acquisition and reconstruction as above) and evaluated by several experienced physicians.

Results: Phantom data show a higher detectability of small spheres for the digital PET/CT system: e.g., the 4.8-mm sphere was solely detectable on the digital system at the highest AC of 25 kBq/mL (Fig. 1a). The CNR was increased for digital PET/CT (Fig. 1b) associated with a MDA reduced by a factor of 0.58 ± 0.13. For the 4.8-mm lesion, dosimetry was calculated based on digital PET/CT data assuming an effective I-131 half-life of 4 d (typical for lymph node metastases) and an administered activity of 25 MBq I-124: An absorbed dose threshold of about 100 Gy, a value associated with a high tumour response rate, could be achieved using a clinically justifiable therapeutic activity of about 6 GBq I-131 (Fig. 1c). The preliminary clinical data show an improved detection of I-124-avid lesions on the digital system: In patient 1, pulmonary lesions became more clearly discernible (Fig. 2). In patient 2, a former invisible lymph node metastasis was identified (Fig. 3a). In patients 5 and 6, uncertain lesions could be excluded (Fig. 3b) or confirmed (Fig. 3c). In patients 3 and 4, no tumour lesions were detected on both systems.

Conclusions: A significantly higher detection sensitivity for I-124 by digital PET/CT was observed in clinical and phantom settings. The greatly improved time resolution of the digital system (214ps) and a smaller crystal size (3.2 mm) contribute to the superior performance. DTC patients will potentially benefit from detection and treatment of former invisible metastases, e.g., by dosimetry-based RIT or targeted surgery. The findings will be further clinically evaluated.