Abstract
Antibody-based therapies gain momentum in clinical therapy, thus the need for accurate imaging modalities with respect to target identification and therapy monitoring are of increasing relevance. Cerenkov luminescence imaging (CLI) are a novel method detecting charged particles emitted during radioactive decay with optical imaging. Here, we compare Position Emission Tomography (PET) with CLI in a multimodal imaging study aiming at the fast and efficient screening of monoclonal antibodies (mAb) designated for targeting of the neuroblastoma-characteristic epitope disialoganglioside GD2. Neuroblastoma-bearing SHO mice were injected with a 64Cu-labeled GD2-specific mAb. The tumor uptake was imaged 3 h, 24 h and 48 h after tracer injection with both, PET and CLI, and was compared to the accumulation in GD2-negative control tumors (human embryonic kidney, HEK-293). In addition to an in vivo PET/CLI-correlation over time, we also demonstrate linear correlations of CLI- and γ-counter-based biodistribution analysis. CLI with its comparably short acquisition time can thus be used as an attractive one-stop-shop modality for the longitudinal monitoring of antibody-based tumor targeting and ex vivo biodistribution.These findings suggest CLI as a reliable alternative for PET and biodistribution studies with respect to fast and high-throughput screenings in subcutaneous tumors traced with radiolabeled antibodies. However, in contrast to PET, CLI is not limited to positron-emitting isotopes and can therefore also be used for the visualization of mAb labeled with therapeutic isotopes like electron emitters.
Highlights
Non-invasive visualization of tumor occurrence and therapeutic monitoring with a special focus on early therapeutic response assessment are increasingly gaining importance in clinical routine
The radioactive decay was measured via Cerenkov luminescence imaging (CLI) for 24 h with initially measured average radiances of 1.09, 0.53, 0.23, and 0.16 x 106p/s/cm2/sr, respectively (Figure 1C), average radiance and activity concentration were linearly correlated over the course of the 24 h measurement (R2 = 0.997, Figure 1C)
Several studies already pointed towards the feasibility and benefits in using Cerenkov radiation as a method to detect radioactive agents with optical imaging, ranging from basic phantom feasibility studies to in vivo applications for, e.g., 18F-FDG detection in brown adipose tissue [23] where the benefits of the superficial position www.impactjournals.com/oncotarget and fast acquisition times were demonstrated
Summary
Non-invasive visualization of tumor occurrence and therapeutic monitoring with a special focus on early therapeutic response assessment are increasingly gaining importance in clinical routine. With the availability of new therapeutic agents such as highly specific antibodies targeting tumor or vascular epitopes, the non-invasive detection of such expressed epitopes in vivo is gaining attention. The non-invasive identification of tumor specific epitopes and possible changes of www.impactjournals.com/oncotarget their expression under therapy are important clinical imperatives and would be of high predictive value in considering potential therapy response [2]. The identification of potential therapeutic targets, as well as the in vivo evaluation and stratification of molecular therapeutics while avoiding pharmacodynamic effects are clear advantages of PET [3, 4]. PET imaging requires expensive tomographic systems and is usually characterized by measurement times ranging from 10-20 min for static imaging studies and up to 60-90 min for dynamic PET assessments [5, 6]
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