Liangjie Lin ^1* Zhiliang Wei ^2,3 Jing Wang ^4,5 Nian Wang ^6,7,8

• ¹ Clinical and Technical Support, Philips Healthcare, Beijing, China
• ² Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United States
• ³ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States
• ⁴ Department of Radiology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
• ⁵ Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
• ⁶ Advanced Imaging Research Center, Medical School, University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ⁷ Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, Texas, United States
• ⁸ Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas, United States

It is becoming increasingly evident that altered metabolism contributes to tumor progression and has been recognized as a hallmark of cancer. The cancer metabolic heterogeneity may result from genetic diversity, complex metabolic pathways, and altered microenvironmental conditions in tumors. Imaging tumor metabolism has been remarkably successful in recent years. Numerous studies demonstrated that malignant tumors could be detected with high sensitivity and specificity by imaging their increased metabolic rates for glucose, amino acids, or lipids [1][2][3]. However, there remain emerging needs for extended studies on the metabolic dependencies of human cancer in vivo to understand how metabolism shapes and defines cancer initiation, progression and response to treatment. Several non-invasive imaging techniques can provide both functional and anatomical information related to tumor metabolism, including positron emission tomography (PET), magnetic resonance imaging (MRI), computed tomography (CT), and optical imaging utilizing bioluminescence etc. These methods may hold the key to helping improve cancer diagnoses and treatments. In this Research Topic "Methods and Applications of Tumor Metabolic Imaging in the Preclinical and Clinical Setting", researchers have demonstrated the potential of different metabolic imaging methods with preclinical and clinical setups for the diagnosis and treatment in a range of tumors.Neoadjuvant chemotherapy (NAC) has become the standard treatment option for locally advanced breast cancer. Early and accurate prediction of tumor response to NAC is critical for treatment management. Currently, there is still no standard method or imaging biomarker in clinical practice to accurately predict the pathological complete response (pCR) to NAC in breast cancer patients. Amide proton transfer weighted (APTw) imaging, which detects the exchange between water protons and amide protons in endogenous mobile proteins or polypeptides in tissues, enables indirect detection of changes in protein synthesis and related pathophysiological features in living cells. Zhang et al. [4] hypothesized that APTw imaging may be a potential tool for assessing the response of breast cancer (especially, the early response) to NAC. And results demonstrated that high sensitivity performance can be achieved by APTw for early prediction of MHR status at the end of the first two NAC cycles, which might allow timely regimen refinement before definitive surgical treatment. APTw in combination with tumor diameter and diffusion weighted imaging can further improve diagnostic accuracy.Benefits from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising in clinical attempts but inconclusive. And it is necessary to carry out a comprehensive investigation on the efficacy of boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI). The study by Gertsenshteyn et al. [5] presents data in three preclinical mammalian tumor types to demonstrate that accurate targeting of hypoxic tumor subvolumes with a boost of radiation improves the local tumor control probability relative to a boost of the same integral dose to oxygenated regions of the tumor. This provides additional biologic validation of EPROI in targeting enough resistant hypoxic tumor subvolumes to increase the probability of eliminating all clonogens. It may provide a means of reducing the dose to oxygenated regions and delivering a radiation boost to resistant hypoxic regions. The boosting hypoxic subvolumes defined by EPROI can also help reduce dose to potential organs at risk when improves tumor control, promising the enhancement of the therapeutic ratio.Accurate staging of prostate cancer (PCa) is critical to disease management and treatment planning. Prostate-Specific Membrane Antigen (PSMA) is a transmembrane glycoprotein, overexpressed in prostate cancer cells. PSMA PET/CT, with excellent sensitivity and specificity, has now become the preferred staging modality for prostate cancer. Compared to other PSMAtargeted tracers, 18 F-PSMA-1007 is mainly cleared by the liver and bile (reduced urinary radioactive interference) thus allowing better assessment of lesions in the prostate and pelvic regions. However, obvious concentrations of 18 F-PSMA-1007 can still be observed in the bladder of some patients, which affects detection of lesions in the prostate and adjacent areas, especially in patients with clinical suspicion of biochemical recurrence, as long-term androgen deprivation therapy will significantly reduce the visibility of prostate lesions on PSMA PET/CT. Dang et al. [6] proposed to explore the cause of the high uptake of 18 F-PSMA-1007 in bladder urine by assessing the clinical characteristics and imaging characteristics of PCa patients. And results showed no significant correlation of the high uptake of 18 F-PSMA-1007 in bladder urine with age, height, weight, Gleason score, metastases, treatment methods, liver and kidney function levels, TPSA levels, 18 F-PSMA-1007 injected activity, the interval from injection to scan, the physiological distribution of parotid gland, kidney, liver, spleen, intestine, obturator internus, and the pathological distribution of prostate lesions. Therefore, more research is still needed to find out the causes of this problem, so as to improve the disease assessment in PCa patients.The PET detection of the radioactive glucose analog 2-18 F-fluoro-2-deoxy-d-glucose ( 18 FDG) is now widely used for tumor metabolic imaging. However, 18 FDG-PET often provides ambiguous results in organs with intrinsic high glucose uptake (such as the brain) and does not inform on metabolism downstream of glucose uptake. Deuterium metabolic imaging (DMI), with combination of deuterium magnetic resonance spectroscopic imaging with oral intake or intravenous infusion of nonradioactive 2 H-labeled substrates, can noninvasively reveal the glucose metabolism flux through the measurement of down-stream deuterated metabolites. A great example is to detect the Warburg effect in cancer metabolism by measuring the conversion of glucose-6,6-D 2 into deuterated lactate, glutamine, and glutamate. The review by Wan et al. [7] explored the latest developments and applications of DMI in oncology across various tumor metabolic axes, with emphasis on its potential for clinical translation. DMI offers invaluable insights into tumor biology, treatment responses (notably, the early responses to immunotherapy), and prognostic outcomes. The conclusion is that DMI may evolve into a convenient and efficient imaging technique and promote precision medicine by improving the diagnosis and evaluation of cancer treatments.