Beyond fluorodeoxyglucose: Molecular imaging of cancer in precision medicine

Abstract

Cancer molecular imaging is the noninvasive visualization of a process unique to or altered in neoplasia, such as proliferation, glucose metabolism, and receptor expression, which is relevant to patient management. Several molecular imaging modalities are now available, including magnetic resonance, optical, and nuclear imaging. Nuclear imaging, particularly using fluorine-18-fluorodeoxyglucose positron emission tomography, is widely used in the staging and response assessment of multiple cancer types. However, at this writing, new nuclear medicine probes, especially positron emission tomography tracers, are increasingly used or are being investigated for cancer evaluation. This review focuses on these probes, their biologic targets, and the applications or potential applications for their use in the assessment of various neoplasms, including both probes available for commercial use-such as somatostatin receptor ligands in neuroendocrine tumors, prostate-specific membrane antigen ligands in prostate cancer, norepinephrine analogs in neural crest tumors like neuroblastoma, and estrogen analogs in breast cancer-and others in clinical development, such as fibroblast-activating protein inhibitors, C-X-C chemokine receptor type 4 ligands, and monoclonal antibodies targeting receptor tyrosine kinases, CD4-positive or CD8-positive tumor-infiltrating lymphocytes, tumor-associated macrophages, and cancer stem cell biomarkers. These developments represent a major step toward the integration of molecular imaging as a powerful tool in precision medicine, with an expectedly significant impact on patient management and outcome.

Keywords: cancer; estrogen receptor; molecular imaging; positron‐emission tomography (PET); precision medicine; prostate‐specific membrane antigen (PSMA); somatostatin analogs.

FIGURE 1

⁶⁸Ga‐DATA5m‐LM4 SSTR antagonist PET/CT detects very small histopathologically proven metastases in both breasts (red circles) in a patient with a well‐differentiated neuroendocrine tumor of the ileum that are not seen on conventional CT or MRI. ⁶⁸Ga‐DATA5m, gallium‐68–labeled (6‐pentanoic acid)‐6‐(amino)methyl‐1,4‐diazepinetriacetate; CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; SSTR, somatostatin receptor.

FIGURE 2

Case example of an excised retroperitoneal paraganglioma with metastasis involving several skeletal regions visible on SSTR ligand ⁶⁸Ga‐DOTANOC imaging. This includes an intensely avid L2 vertebral bone marrow lesion (arrow) showing only mild, nonspecific sclerosis on CT but confirmed by MRI to be a metastasis. CT indicates computed tomography; ⁶⁸Ga‐DOTANOC, gallium‐68–labeled dodecane tetraacetic acid–1‐Nal(3)–octerotide; MRI, magnetic resonance imaging; SSTR, somatostatin receptor.

FIGURE 3

Example of a patient with biochemical prostate cancer recurrence (PSA, 0.25 ng/mL) with a solitary, metastatic, T1 vertebral bone lesion (arrows) best appreciated on PSMA PET. PET indicates positron emission tomography; PSA, prostate‐specific antigen; PSMA, prostate‐specific membrane antigen.

FIGURE 4

(A) Baseline, axial PSMA PET slice through the lower chest and upper abdomen in a patient with CRPC revealing hepatic metastases with uptake greater than normal liver (white circle). (B) Baseline axial FDG PET slice showing negligible FDG uptake in the same liver metastases (white circle) with intense PSMA uptake. (C) After three RLT cycles, the PSA level dropped from approximately 76 ng/mL to approximately 30 ng/mL, and a fourth RLT cycle was given followed by a PSMA scan that revealed a good imaging response in the liver metastases (white circle), with other liver, bone, and lymph node metastases following a similar pattern, resulting in the administration of a fifth RLT cycle. (D) Because of a rising PSA level before the fifth RLT cycle, which was discordant with the good imaging response on PSMA PET, FDG PET was performed to assess for disease dedifferentiation. The FDG PET scan shows increased FDG uptake in the same region of liver metastases (white circle) as well as other metastases (not shown) that were negative on follow‐up PSMA, indicating disease dedifferentiation. CRPC indicates castration‐resistant prostate cancer; CT, computed tomography; FDG, fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography; PSA, prostate‐specific antigen; PSMA, prostate‐specific membrane antigen; RLT, radioligand therapy.

FIGURE 5

A case of biopsy‐proven hepatocellular carcinoma in which (Left) FDG PET was first performed for evaluation before biopsy followed by (Right) FAPI PET when results on FDG, MRI, and CT were inconclusive. FAPI was positive for multifocal liver involvement (arrow), whereas FDG was not suggestive. CT indicates computed tomography; FAPI, fibroblast‐activating protein inhibitor; FDG, fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography.