Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like ⁶⁴Cu-bevacizumab and ⁸⁹Zr-ramucirumab, has emerged as a powerful strategy for non-invasive imaging of VEGFR expression and distribution in vivo. Through positron emission tomography (PET) and single-photon emission computed tomography (SPECT), these targeted tracers enable real-time visualization of angiogenic and lymphangiogenic activity, providing insights into disease progression and therapeutic responses. This review explores the current advances in VEGFR-targeted imaging, focusing on the development of novel tracers, radiolabeling techniques, and their in vivo imaging characteristics. We discuss the preclinical and clinical applications of VEGFR imaging, highlight existing challenges, and provide perspectives on future innovations that could further enhance precision diagnostics and therapeutic monitoring in angiogenesis and lymphangiogenesis-driven diseases.

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of KYN pathway-specific radiotracers.

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[¹⁸F]fluoroethyl)-L-tryptophan (L-[¹⁸F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[¹⁸F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[¹⁸F]FETrp had a comparable tumor uptake with [¹⁸F]fluorodeoxyglucose (FDG). However, L-[¹⁸F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[¹⁸F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan–kynurenine pathway as a therapeutic target for treating NF1.

Purpose: Progressive supranuclear palsy (PSP) is a tauopathy marked by widespread tau aggregation and prominent monoaminergic dysfunction, yet the relationship between regional tau burden and monoaminergic impairment remains unclear. In this study, we determine whether regional tau burden is associated with nigrostriatal monoaminergic dysfunction in PSP using PET imaging. Patients and Methods: A subset of 20 patients with PSP and monoaminergic impairment, identified by ¹⁸ F-FP-DTBZ PET, was recruited and subsequently underwent ¹⁸ F-APN-1607 PET to assess tau deposition. All images were spatially normalized and analyzed based on predefined volumes of interest. Erosion-based cerebral white matter was used as the reference region to calculate standardized uptake value ratios (SUVRs) for ¹⁸ F-APN-1607 PET. Results: The SUVRs of ¹⁸ F-APN-1607 PET differed significantly between patients with PSP and healthy controls in the globus pallidus, substantia nigra, subthalamus nucleus, and red nucleus, while a significant difference in ¹⁸ F-FP-DTBZ SUVRs was observed in all the striatal regions and substantia nigra. Regression analysis discovered negative associations between tau load and monoaminergic disruption in the putamen and caudate, whereas tau accumulation in the substantia nigra was not significantly associated with nigrostriatal impairment. Conclusions: The pallido-nigro-luysian axis and nigrostriatal system serve as sensitive targets for detecting tau deposition and monoaminergic disruption in PSP. Local striatal tau pathology and tau burden were associated with monoaminergic disruption in PSP.