Existing radiotracers for oncology fall into two broad categories including those that localize to tumors based on altered metabolic activity and those that leverage specific ligand-receptor interactions. Oncologic radiotracers can be labeled with either positron-emitting radionuclides for positron emission tomography (PET) or gamma-photon emitting radionuclides for planar imaging or single-photon emission computed tomography (SPECT).

The archetype of metabolic radiotracers is 2-deoxy-2-[18F]fluoro-d-glucose (FDG), a generally applicable oncology PET radiotracer, which has seen a wide use in a variety of applications including breast cancer, colorectal cancer, lymphoma, lung cancer, melanoma, sarcoma, head and neck malignancies, and others [1,2]. However, it is insensitive in a number of common malignancies, including low-grade gliomas, well-differentiated thyroid cancer, pulmonary, bowel, and pancreatic neuroendocrine tumors, low-grade non-small-cell lung cancers, lobular breast cancer, renal cell carcinoma, nonseminomatous germ cell testicular tumors, low-grade ovarian tumors, prostate adenocarcinoma, extranodal marginal zone lymphoma, liposarcoma [2], other low-grade sarcomas, and hepatocellular carcinoma [3], due to reasons of low cellular density, slow growth or division resulting in low FDG consumption, or ability to eject the agent. FDG also has a tendency to be taken up by macrophages in non-malignant conditions such as inflammation [2], which is useful in benign applications such as fever of unknown origin but also decreases specificity considerably as it may be confused with malignancies [4]. FDG also requires abstention from both food and insulin for a period of 4–6 h before injection, which can be problematic for diabetics.

Most other existing oncologic radiotracers are specifically aimed at the weak spots of FDG, including, first of all, gamma-imaging agents such as iodine-123 for well-differentiated thyroid cancer, [123I]MIBG for pheochromocytoma [3], and the various new PET agents that have arisen in recent years such as [68Ga]DOTATATE (DOTA-octreotate) and [68Ga]DOTATOC (edotreotide), which target somatostatin receptors and detect neuroendocrine tumors [5], and PSMA-targeted tracers such as [68Ga]gozetotide, [18F]piflufolastat [6], and [18F]flutofolastat, which detect prostate cancer, more sensitively than prior agents such as [18F]fluciclovine or [11C]choline [7]. While 18F-fluoroestradiol was originally developed to assess estrogen receptor expression in breast cancers [8], it has been used to detect invasive lobular carcinomas, which are too widely distributed in space for FDG to be sensitive.

Despite significant advances in oncology radiotracers that have become regulatory approved in different jurisdictions, there remains a rich pipeline of new agents that have the potential to add new insights into oncologic biology, staging, prognostication, and therapeutic selection and monitoring. For the most part, such emerging radiotracers focus on specific ligand-receptor interactions. The purpose of this review article was to discuss some of the more promising classes of oncology radiotracers that are in clinical development.