Advances and challenges in precision imaging

Abstract

Technological innovations in genomics and related fields have facilitated large sequencing efforts, supported new biological discoveries in cancer, and spawned an era of liquid biopsy biomarkers. Despite these advances, precision oncology has practical constraints, partly related to cancer's biological diversity and spatial and temporal complexity. Advanced imaging technologies are being developed to address some of the current limitations in early detection, treatment selection and planning, drug delivery, and therapeutic response, as well as difficulties posed by drug resistance, drug toxicity, disease monitoring, and metastatic evolution. We discuss key areas of advanced imaging for improving cancer outcomes and survival. Finally, we discuss practical challenges to the broader adoption of precision imaging in the clinic and the need for a robust translational infrastructure.

Fig. 1:. Precision imaging and its role in precision oncology

Precision oncology has historically been defined by the use of genetic mutations to identify patient populations who will respond to a given drug/dose combination. Precision oncology has practical limitations, partly related to cancer’s biological diversity and spatial/temporal complexity. Precision imaging technologies are being developed to address some of the current limitations. These emerging imaging methods strengthen precision oncology by providing clinically relevant information not obtainable by other means (brown box).

Fig. 2:. Examples of precision imaging during the treatment history of cancer.

A. Case history of a patient with cancer. The lesion size is plotted as a function of time and for primary tumor, locoregional invasion, and distant metastases. Note the frequent imaging. B. Role of precision imaging during different cancer stages. The grey boxes with checkmarks represent the main applications. Note: low-dose imaging is mostly for lung cancer (CT) or breast cancer screening (mammography). IO imaging: intraoperative imaging; radiopharmaceutical therapy (RPT).

Fig. 3:. Total-body PET Imaging

Examples of studies enabled by total-body PET scanners that image the entire body at once with high detection sensitivity. A. Maximum-intensity projection (MIP) showing total-body parametric image for blood flow using 11C-butanol and quantified in absolute units of mL blood/min/cm³ tissue calculated with kinetic modeling (adapted, with permission, from). B. MIP of the total-body distribution of [⁸⁹Zr]Zr-crefmirlimab, an antibody fragment that binds to CD8+ T-cells (adapted from). Uptake is observed in the spleen and bone marrow, with exquisite delineation of lymph nodes throughout the body. Image obtained 48 hours post-injection; the injected dose was only 18 MBq to enable repeat imaging.

Fig. 4:. Whole-body PET imaging with new fibroblast activation protein inhibitor (FAPI) tracer.

Thirty-eight-year-old female patient with a solitary fibrous tumor of the right abdominal wall presenting with lung, peritoneal and bone metastases. A. The left two images represent [¹⁸F]FDG PET maximum projection images before and after 4 cycles of treatment. B. As the patient exhausted all treatment options, a [⁶⁸Ga]Ga-FAPI-46 PET-CT was performed (second from right), displaying high FAP uptake in all [¹⁸F]FDG-avid lesions. After four cycles of ⁹⁰Y-FAPI-46 RLT, restaging revealed partial response according to RECIST criteria. Figure courtesy of Helena Lanzafame, Rainer Hamacher and Wolfgang Fendler (Universitätsmedizin Essen, Germany).

Fig. 5:. Therapeutic approaches involving radiotheranostics.

Therapeutic effects on cancer cells caused by DNA damage induced by either α-, β- or auger-emitting radionuclides can be enhanced via combination with drugs that either cause direct damage to DNA (such as chemotherapies) or inhibit DNA damage repair directly (such as PARP inhibitors) or through modulation of the associated signaling pathways (e.g., with novel androgen-deprivation therapies). Radiotheranostics can also target the tumor microenvironment (fibroblast activation protein) and kill stromal cells, which can indirectly lead to tumor regression. Bystander effects, owing to the use of β-emitters, on the DNA of cancer cells that do not express radiotheranostic target proteins can nonetheless lead to tumor cell death. Targeted radionuclide therapies might also induce antigen presentation following cancer cell death and, when combined with immune checkpoint inhibitors, lead to enhanced antitumor activity. DDR: DNA damage response.

Fig. 6:. Fiberoptic and intraoperative imaging

Fluorescence-based cellular and molecular imaging is an up-and-coming modality, primarily employed for endoscopic and intraoperative imaging. A: results from fluorescent guided surgical detection of residual tumor in the resection cavity using the recently FDA-approved Lumicell system^,. B: the use of bioorthogonal chemistry has enabled, in vivo, cyclic imaging for up to 12 different targets.