Amino Acid-Based Fluciclovine PET/CT Detection of Multiple Myeloma

Introduction

Positron emission tomography (PET) with 2-Deoxy-2-[¹⁸F]-fluoroglucose (FDG) in multiple myeloma (MM) is prognostic both at presentation and in remission, and is currently the best technology to demonstrate patchy and extramedullary disease [Cavo et al. Lancet Oncol. 2017; Moreau et al. J Clin Oncol. 2017]. However, FDG PET has some limitations, such as low sensitivity in detecting early bone marrow infiltration, and that 8-10 % of MM patients are FDG negative at diagnosis. Furthermore, FDG is highly unspecific and both inflammation and increased metabolic activity in relation to the repair process give increased FDG uptake and might be difficult to distinguish from active disease. In two recent studies, imaging with the amino acid tracer ¹¹C-Methionine showed higher sensitivity for intra- and extramedullary MM in comparison to FDG [Lapa et al. Theranostics. 2017; Imataki et al. Clin Nucl Med. 2017]. Unfortunately, the short half-life of carbon-11 (20 minutes) renders this tracer inconvenient for many centers. Fluciclovine (anti-1-amino-3-[¹⁸F]-fluorocyclobutane-1-carboxylic acid) is an amino acid-based PET tracer analogous to leucine with a half-life of 110 minutes. It was recently approved by the Food and Drug Administration for detection of prostate cancer recurrence in patients with elevated PSA levels.

The aim of this study is to investigate the visual and semi-quantitative performance of Fluciclovine PET compared to FDG PET for MM patients, with the intention of improving the quality of nuclear imaging in myeloma. The study will also include evaluations of optimal imaging protocols based on tracer kinetics.

Methods

Twelve newly diagnosed transplant eligible MM patients were included and assessed both with FDG PET/CT and Fluciclovine PET/CT according to the study protocol before (Time point 0 (Tp0)) and 3 months after autologous stem cell transplantation(ASCT) (Tp1).

The study was approved by the National Ethic Committee (2018/2212/REK) and the Norwegian Medical Agency. ClinicalTrials.gov Identifier: NCT03966443.

Fluciclovine 313-360 MBq was injected and PET imaging was repeated at several time points; approx. 15, 30, 60 and 120 minutes post injection (p.i.) in the first three patients (two to three times in each patient) with 2.5 min/bed position. For all later scans a dynamic imaging (0-15 min p.i.) over the lumbar area and a whole body acquisition 15 min p.i. with 1 min/bed position were performed. FDG PET scans were performed within one week of Fluciclovine PET on the same scanner (Discovery MI PET/CT scanner (GE Healthcare)) for comparison.

Results

Twelve patients have been evaluated at diagnosis and nine of them three months after ASCT treatment. Data from all twelve patients will be available before the meeting. Acquisitions at 15 minutes p.i. and of a duration less than 15 minutes for a whole-body examination produced satisfactory image quality. At diagnosis, seven patients demonstrated higher uptake and/or far more positive focal lesions compared to the FDG PET. Three patients were suspected positive on Fluciclovine PET with high and heterogeneous bone marrow uptake when FDG PET showed no pathological uptake. In two patient Fluciclovine PET and FDG PET performed equally, while one patient was assessed to be probably negative on both examinations. No patient had higher uptake on FDG PET. All patients with positive Fluciclovine PET showed good treatment response 3 months after ASCT while FDG was not able to evaluate response in four patients.

Conclusions

Based on this pilot study, Fluciclovine is a promising amino acid-based PET tracer for both diagnosis and treatment evaluation in MM patients, with higher uptake and more focal lesions than FDG PET. The tracer has beneficial technical characteristics, with a half-life of 110 minutes allowing transport, short p.i time and rapid acquisition time.

Figure 1: Patient A: A 58-years old female imaged with Fluciclovine PET and FDG PET at diagnosis and 3 months after ASCT. Patient B: A 48-years old male imaged with Fluciclovine PET and FDG PET at diagnosis and 3 months after ASCT.