(Open access funding provided by Semmelweis University)
(739593) Funder: Horizon 2020
(128322) Funder: NR-DIO
Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery
and pathological sampling. It could offer additional advantages when combined to whole-body
isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma
patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of
combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell
lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early
stage, and at clinically relevant stages such as advanced stage and terminal stage
with in vivo 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/magnetic
resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography
(SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use
of CLI with 18F-Fluorine (F-18) and 67Ga-Gallium isotopes in the selection of infiltrated
lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG
PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated
tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we
could report in vivo detection of the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate
revealed lymphoma accumulation in distant lymph node locations, unnoticeable with
only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results.
Our study promotes the combined use of PET and CLI in preclinical studies and clinical
practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery,
has implications for tissue pathology processing and it could direct therapy. The
results with 67Ga also point to the opportunities to further apply suitable SPECT
radiopharmaceuticals for CLI.
