Landscape of Nuclear Medicine in China and Its Progress on Theranostics.

Nuclear medicine in China started in 1956 and, with the rapid development of the economy and continuous breakthroughs in precision medicine, has made significant progress in recent years. Almost 13,000 staff members in nearly 1,200 hospitals serve more than 3.9 million patients each year. Over the past decade, the radiopharmaceutical industry has developed rapidly, with the initial formation of a complete industrial chain of production of various radiopharmaceuticals for both clinical use and basic research. Advanced equipment such as PET/CT scanners is being manufactured domestically and even installed abroad. Recently, research into screening and synthesizing new target probes and their translation into the clinic has gained more attention, with various new tracers with potential clinical value being thoroughly studied. Simultaneously, 68Ga- and 177Lu-labeled tumor-targeted probes and others have been implemented for theranostics in an increasing number of hospitals and would be helped by approval from the National Medical Products Administration. Over the next 10-20 y, with the launch of the Mid- and Long-Term Development Plan for Medical Isotopes (2021-2035) by the Chinese government, there is great potential for nuclear medicine in China. With the rise in independent innovation in manufacturing, the shortage of radiopharmaceuticals will be effectively curtailed. We anticipate that the scale of nuclear medicine will at least double by 2035, covering all high-grade hospitals and leading to the aim of "one county, one department" in China.

Fibroblast Activation Protein Inhibitor Tracers and Their Preclinical, Translational, and Clinical Status in China.

Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors.

Melanin-Targeting Radiotracers and Their Preclinical, Translational, and Clinical Status: From Past to Future.

Melanin is one of the representative biomarkers of malignant melanoma and a potential target for diagnosis and therapy. With advancements in chemistry and radiolabeling technologies, promising strides have been made to synthesize radiolabeled melanin-binding molecules for various applications. We present an overview of melanin-targeted radiolabeled molecules and compare their features reported in preclinical studies. Clinical practice and trials are also discussed to elaborate on the safety and validity of the probes, and expanded applications beyond melanoma are reviewed. Melanin-targeted imaging holds potential value in the diagnosis, staging, and prognostic assessment of melanoma and other applications. Melanin-targeted radionuclide therapy possesses immense potential but requires more clinical validation. Furthermore, an intriguing avenue for future research involves expanding the application scope of melanin-targeted probes and exploring their value.

Development and evaluation of albumin binder-conjugated heterodimeric radiopharmaceuticals targeting integrin αvß3 and CD13 for cancer therapy.

PURPOSE: The advancement of heterodimeric tracers, renowned for their high sensitivity, marks a significant trend in the development of radiotracers for cancer diagnosis. Our prior work on [68Ga]Ga-HX01, a heterodimeric tracer targeting CD13 and integrin αvß3, led to its approval for phase I clinical trials by the China National Medical Production Administration (NMPA). However, its fast clearance and limited tumor retention pose challenges for broader clinical application in cancer treatment. This study aims to develop a new radiopharmaceutical with increased tumor uptake and prolonged retention, rendering it a potential therapeutic candidate. METHODS: New albumin binder-conjugated compounds were synthesized based on the structure of HX01. In vitro and in vivo evaluation of these new compounds were performed after labelling with 68Ga. Small-animal PET/CT imaging were conducted at different time points at 0.5-6 h post injection (p.i.) using BxPC-3 xenograft mice models. The one with the best imaging performance was further radiolabeled with 177Lu for small-animal SPECT/CT and ex vivo biodistribution investigation. RESULTS: We have synthesized novel albumin binder-conjugated compounds, building upon the structure of HX01. When radiolabeled with 68Ga, all compounds demonstrated improved pharmacokinetics (PK). Small-animal PET/CT studies revealed that these new albumin binder-conjugated compounds, particularly [68Ga]Ga-L6, exhibited significantly enhanced tumor accumulation and retention compared with [68Ga]Ga-L0 without an albumin binder. [68Ga]Ga-L6 outperformed [68Ga]Ga-L7, a compound developed using a previously reported albumin binder. Furthermore, [177Lu]Lu-L6 demonstrated rapid clearance from normal tissues, high tumor uptake, and prolonged retention in small-animal SPECT/CT and biodistribution studies, positioning it as an ideal candidate for radiotherapeutic applications. CONCLUSION: A new integrin αvß3 and CD13 targeting compound was screened out. This compound bears a novel albumin binder and exhibits increased tumor uptake and prolonged tumor retention in BxPC-3 tumors and low background in normal organs, making it a perfect candidate for radiotherapy when radiolabeled with 177Lu.

Voltage-gated potassium channel 1.3: A promising molecular target in multiple disease therapy.

Voltage-gated potassium channel 1.3 (Kv1.3) has emerged as a pivotal player in numerous biological processes and pathological conditions, sparking considerable interest as a potential therapeutic target across various diseases. In this review, we present a comprehensive examination of Kv1.3 channels, highlighting their fundamental characteristics and recent advancements in utilizing Kv1.3 inhibitors for treating autoimmune disorders, neuroinflammation, and cancers. Notably, Kv1.3 is prominently expressed in immune cells and implicated in immune responses and inflammation associated with autoimmune diseases and chronic inflammatory conditions. Moreover, its aberrant expression in certain tumors underscores its role in cancer progression. While preclinical studies have demonstrated the efficacy of Kv1.3 inhibitors, their clinical translation remains pending. Molecular imaging techniques offer promising avenues for tracking Kv1.3 inhibitors and assessing their therapeutic efficacy, thereby facilitating their development and clinical application. Challenges and future directions in Kv1.3 inhibitor research are also discussed, emphasizing the significant potential of targeting Kv1.3 as a promising therapeutic strategy across a spectrum of diseases.

Different Ectopic Endocrine Tumors on Renal Hilum Detected by 68Ga-DOTATATE PET.

ABSTRACT: Renal hilum is a very rare location for primary adrenocortical adenoma or pheochromocytoma. We report 68Ga-DOTATATE PET/CT findings of primary renal hilar adrenocortical adenoma in one patient and 68Ga-DOTATATE PET/MR findings of pheochromocytoma in another patient.

Tau induces inflammasome activation and microgliosis through acetylating NLRP3.

BACKGROUND: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive. METHODS: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function. RESULTS: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice. CONCLUSIONS: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies.

[18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy.

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients. METHODS: Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions. RESULTS: For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. 'not reached' [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ -46.76] vs. 'not reached' [∆SUVmax% < -46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman's rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001). CONCLUSION: In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.

Case report: Exploring the utility of whole-body bone scintigraphy for pediatric Langerhans cell histiocytosis: insights from clinical practice.

Purpose: This mini-review delves into the realm of Langerhans cell histiocytosis (LCH) in children, focusing on its skeletal involvement. By synthesizing pertinent literature, we sought to provide a comprehensive understanding of LCH's clinical and radiographic spectrum. Our study then demonstrates the diagnostic prowess of whole-body 99mTc-methyl diphosphonate (MDP) scintigraphy in LCH cases, underscoring its value in tandem with existing knowledge. Methods: Our approach involved an extensive literature review that contextualized LCH within the current medical landscape. Subsequently, we presented a case series featuring five pediatric instances of skeletal LCH, one accompanied by soft tissue infiltration. The principal aim was to illuminate the diagnostic and staging potential of whole-body 99mTc-MDP scintigraphy, augmenting existing insights. Results: Through meticulous literature synthesis, we highlighted pediatric LCH's protean clinical manifestations and radiological variability. Aligning with this spectrum, our case series underscored the role of 99mTc-MDP scintigraphy in diagnosing and staging LCH. Among the five pediatric cases, one demonstrated concurrent soft tissue involvement. This aligns with the multifaceted nature of LCH presentations. Conclusion: Pediatric LCH can present with a wide range of clinical and radiologic features. By amalgamating our cases with extant literature, we stress the necessity of a multimodal strategy. 99mTc-MDP scintigraphy emerged as an indispensable tool for accurate staging and soft tissue detection. Our findings collectively advocate for a holistic approach to managing LCH, ensuring informed therapeutic decisions for optimal patient outcomes.

Surgical evidence-based comparison of [68Ga]Ga-FAPI-04 PET and MRI-DWI for assisting debulking surgery in ovarian cancer patients.

PURPOSE: Imaging assessment of abdominopelvic tumor burden is crucial for debulking surgery decision in ovarian cancer patients. This study aims to compare the efficiency of [68Ga]Ga-FAPI-04 FAPI PET and MRI-DWI in the preoperative evaluation and its potential impact to debulking surgery decision. METHODS: Thirty-six patients with suspected/confirmed ovarian cancer were enrolled and underwent integrated [68Ga]Ga-FAPI-04 PET/MRI. Nineteen patients (15 stage III-IV and 4 I-II stage) who underwent debulking surgery were involved in the diagnostic efficiency analysis. The images of [68Ga]Ga-FAPI-04 PET and MRI-DWI were visually analyzed respectively. Immunohistochemistry on FAP was performed in metastatic lesions to investigate the radiological missing of [68Ga]Ga-FAPI-04 PET as well as its different performance in primary debulking surgery (PDS) and interval debulking surgery (IDS) patients. Potential imaging impact on management was also studied in 35 confirmed ovarian cancer patients. RESULTS: [68Ga]Ga-FAPI-04 PET displayed higher sensitivity (76.8% vs.59.9%), higher accuracy (84.9% vs. 80.7%), and lower missing rate (23.2% vs. 40.1%) than MRI-DWI in detecting abdominopelvic metastasis. The diagnostic superiority of [68Ga]Ga-FAPI-04 PET is more obvious in PDS patients but diminished in IDS patients. [68Ga]Ga-FAPI-04 PET outperformed MRI-DWI in 70.8% abdominopelvic regions (17/24), which contained seven key regions that impact the resectability and surgical complexity. MRI-DWI hold advantage in the peritoneal surface of the bladder and the central tendon of the diaphragm. Of the contradictory judgments between the two modalities (14.9%), [68Ga]Ga-FAPI-04 PET correctly identified more lesions, particularly in PDS patients (73.8%). In addition, FAP expression was independent of lesion size and decreased in IDS patients. [68Ga]Ga-FAPI-04 PET changed 42% of surgical planning that was previously based on MRI-DWI. CONCLUSION: [68Ga]Ga-FAPI-04 PET is more efficient in assisting debulking surgery in ovarian cancer patients than MRI-DWI. Integrated [68Ga]Ga-FAPI-04 PET/MR imaging is a potential method for planning debulking surgery in ovarian cancer patients.

Congenital Mesoblastic Nephroma Mimic Wilms Tumor on 18 F-FDG PET/CT and PET/MR.

ABSTRACT: Congenital mesoblastic nephroma is an extremely rare, low-grade malignant renal tumor in children. A 10-month-old boy and a 4-month-old girl were admitted to our hospital with a huge abdominal mass. For staging of the mass, 18 F-FDG PET/CT and PET/MR were performed showing a huge heterogeneous abdominal mass accompanied by extensive heterogeneous aggregation. Both of them were highly suspected to be Wilms tumor, the most common renal malignant tumor in children. However, histopathological examination after surgery confirmed congenital mesodermal nephroma.

Construction of truncated PSMA as a PET reporter gene for CAR T cell trafficking.

In solid tumors, there are multiple barriers for a chimeric antigen receptor (CAR) T cell to surmount in order to reach the tumor site. For better understanding whether CAR T cells effectively infiltrate into tumor site, and simultaneously, whether there are off-target effects, real-time monitoring technologies need to be established. Cell-based positron emission tomography reporter genes have been developed to monitor engineered cells in living subjects. In this study, we reported the construction of a novel reporter gene truncated prostate-specific membrane antigen (ΔPSMA) pending for monitoring CAR T cells using 68Ga-PSMA-617 and a method for tracking the distribution of CAR T cells in vivo was developed. Data were provided to demonstrate that ΔPSMA was predominantly localized on the plasma membrane and could take up 68Ga-PSMA-617 in vitro in a time-dependent manner. And the expression of ΔPSMA did not affect CAR expression and cytolytic capacity of CAR T cells. CAR-ΔPSMA T cell xenografts in nude mice were clearly imaged by positron emission tomography 60 min after injection of 68Ga-PSMA-617. PSMA paired with 68Ga-PSMA-617 was capable of identifying approximately 1 × 104 engineered CAR T cells. The ability to image small numbers of CAR T cells in vivo would be helpful to accelerate the translation of cell-based therapies into the clinic, and it may reinforce our understanding of treatment success, failure, and toxicity.

Noninvasive longitudinal PET/CT imaging of CAR T cells using PSMA reporter gene.

PURPOSE: Chimeric antigen receptor (CAR) T cell therapy has achieved great success in treating hematologic malignancies. However, it is yet to prove effective in the treatment of solid tumors. Thus, it is necessary to develop appropriate methodology for the long-term, accurate, and quantitative evaluation of the distribution and activities of CAR T cells in solid tumors. In the present study, we engineered TfR ΔPSMA CAR (CAR-ΔPSMA) T cells, which targeted the transferrin receptor (TfR) expressed by tumor cells and could be tracked in vivo via a reporter gene encoding the truncated prostate specific membrane antigen (ΔPSMA). We then quantitatively monitored these CAR T cells in vitro and in vivo using [68Ga]Ga-PSMA-617 positron emission tomography (PET)/computed tomography (CT). METHODS: The CAR-ΔPSMA T cells were genetically engineered by transducing T cells with a lentiviral vector encoding TfR41BBζ-T2A-ΔPSMA. Firstly, the target expression, activation, and cytotoxicity of CAR-ΔPSMA T cells were validated in vitro. Secondly, the minimum thresholds of CAR-ΔPSMA T cells detection for [68Ga]Ga-PSMA-617 PET/CT were also determined in vitro and in vivo respectively. Lastly, the feasibility of monitoring the biodistribution and infiltration of CAR-ΔPSMA T cells after systematic administration was evaluated in the breast cancer subcutaneous xenograft model. RESULTS: The CAR-ΔPSMA T cells retained activation and tumor killing capacity after transduction of the ΔPSMA-encoding reporter gene. Next, the CAR-ΔPSMA T cells could be reliably tracked by [68Ga]Ga-PSMA-617 PET/CT, the detection sensitivity of which was 250 cells/mm3 in vitro and 100 cells/mm3 in vivo. Next, the sequential imaging assays revealed that [68Ga]Ga-PSMA-617 PET/CT could be used to specifically visualize ΔPSMA+ CAR T cells at the tumor site. The increase in the [68Ga]Ga-PSMA-617 signal intensity over time allowed us to effectively detect CAR T cells in vivo. CONCLUSION: Our findings preliminarily confirmed that [68Ga]Ga-PSMA-617 PET/CT could reliably detect CAR-ΔPSMA T cells in vitro and in vivo in solid tumors, laying the foundation for the monitoring CAR T cell therapy in the future.

Added value of regional 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in malignant ascites with unknown primary origin.

BACKGROUND: Comparing to PET/CT, integrative PET/MRI imaging provides superior soft tissue resolution. This study aims to evaluate the added value of regional delayed 18F-FDG PET/MRI-assisted whole-body 18F-FDG PET/CT in diagnosing malignant ascites patients. RESULTS: The final diagnosis included 22 patients with ovarian cancer (n = 11), peritoneal cancer (n = 3), colon cancer (n = 2), liver cancer (n = 2), pancreatic cancer (n = 2), gastric cancer (n = 1), and fallopian tube cancer (n = 1). The diagnosis of the primary tumor using whole-body PET/CT was correct in 11 cases. Regional PET/MRI-assisted whole-body PET/CT diagnosis was correct in 18 cases, including 6 more cases of ovarian cancer and 1 more case of fallopian tube cancer. Among 4 cases that were not diagnosed correctly, 1 case had the primary tumor outside of the PET/MRI scan area, 2 cases were peritoneal cancer, and 1 case was colon cancer. The diagnostic accuracy of regional PET/MRI-assisted whole-body PET/CT was higher than PET/CT alone (81.8% vs. 50.0%, κ 2 = 5.14, p = 0.023). The primary tumor conspicuity score of PET/MRI was higher than PET/CT (3.67 ± 0.66 vs. 2.76 ± 0.94, P < 0.01). In the same scan area, more metastases were detected in PET/MRI than in PET/CT (156 vs. 86 in total, and 7.43 ± 5.17 vs. 4.10 ± 1.92 per patient, t = 3.89, P < 0.01). Lesion-to-background ratio in PET/MRI was higher than that in PET/CT (10.76 ± 5.16 vs. 6.56 ± 3.45, t = 13.02, P < 0.01). CONCLUSION: Comparing to whole-body PET/CT alone, additional delayed regional PET/MRI with high soft tissue resolution is helpful in diagnosing the location of the primary tumor and identifying more metastases in patients with malignant ascites. Yet larger sample size in multicenter and prospective clinical researches is still needed.

Coexistence of FDG-Avid and FDG-Negative Aneurysms in a Patient With Fever of Unknown Origin.

ABSTRACT: A 68-year-old man with intermittent fever of unknown origin for 5 months underwent 18F-FDG PET/CT to detect causative lesion. An 18F-FDG-avid lesion was revealed in the left pelvic iliac vessel region and was highly suggestive of malignancy. One and a half months later, a giant left internal iliac artery aneurysm was identified by CT angiography, corresponding to the 18F-FDG-avid lesion. Combined with elevated inflammatory markers, he was finally diagnosed as having inflammatory internal iliac artery aneurysm. An abdominal aortic aneurysm with low 18F-FDG uptake was also identified.

Melanin-targeted [18F]-PFPN PET imaging may shed light for clear cell sarcoma.

PURPOSE: Intracytoplasmic melanin pigment is a characteristic of clear cell sarcoma (CCS), which is a particularly deadly type of soft-tissue sarcoma. [18F]-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ([18F]-PFPN) is a positron emission tomography (PET) probe characterized by high melanin affinity. Therefore, this study aimed to investigate the feasibility of melanin-targeted [18F]-PFPN PET in patients with CCS. METHODS: This prospective single-centre study recruited patients with pathologically confirmed CCS. [18F]-FDG PET/computed tomography and [18F]-PFPN PET/magnetic resonance imaging scans were performed within 1 week of each other. The lesion numbers and [18F]-FDG and [18F]-PFPN PET parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic/melanotic tumour volume [MTV/MLTV], and total lesion glycolysis/melanin [TLG/TLM]) were collected. RESULTS: Three patients with CCS were recruited and received PET imaging. A total of 56 lesions were detected on [18F]-PFPN PET, including primary tumour and distant metastases. Identical lesions were not detected on [18F]-PFPN and [18F]-FDG PET. Twelve lesions (12/39, 30.77%) on [18F]-FDG imaging were missed on [18F]-PFPN, and 20 lesions (20/47, 42.55%) on [18F]-PFPN imaging were missed on [18F]-FDG. In quantitative analysis, the [18F]-FDG SUVmean (4.60 ± 3.24) was higher than the [18F]-PFPN SUVmean (3.0 ± 2.63) in all lesions (P = 0.01). No significant correlations were found between the SUVmax, SUVmean, MLTV/MTV, and TLM/TLG values of [18F]-PFPN and [18F]-FDG (P > 0.05). CONCLUSION: Melanin-targeted [18F]-PFPN PET imaging is feasible for the diagnosis of CCS. Different imaging features were displayed on [18F]-PFPN and [18F]-FDG PET imaging, demonstrating the complementary role of the tracers. Combined use of the two imaging modalities would be preferred in patients with CCS. CLINICAL TRIAL REGISTRATION: NCT05963035.