Nanomedicine for renal cell carcinoma: imaging, treatment and beyond.

The kidney is a vital organ responsible for maintaining homeostasis in the human body. However, renal cell carcinoma (RCC) is a common malignancy of the urinary system and represents a serious threat to human health. Although the overall survival of RCC has improved substantially with the development of cancer diagnosis and management, there are various reasons for treatment failure. Firstly, without any readily available biomarkers, timely diagnosis has been greatly hampered. Secondly, the imaging appearance also varies greatly, and its early detection often remains difficult. Thirdly, chemotherapy has been validated as unavailable for treating renal cancer in the clinic due to its intrinsic drug resistance. Concomitant with the progress of nanotechnological methods in pharmaceuticals, the management of kidney cancer has undergone a transformation in the recent decade. Nanotechnology has shown many advantages over widely used traditional methods, leading to broad biomedical applications ranging from drug delivery, prevention, diagnosis to treatment. This review focuses on nanotechnologies in RCC management and further discusses their biomedical translation with the aim of identifying the most promising nanomedicines for clinical needs. As our understanding of nanotechnologies continues to grow, more opportunities to improve the management of renal cancer are expected to emerge.

Customizing cancer treatment at the nanoscale: a focus on anaplastic thyroid cancer therapy.

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive kind of thyroid cancer. Various therapeutic methods have been considered for the treatment of ATC, but its prognosis remains poor. With the advent of the nanomedicine era, the use of nanotechnology has been introduced in the treatment of various cancers and has shown great potential and broad prospects in ATC treatment. The current review meticulously describes and summarizes the research progress of various nanomedicine-based therapeutic methods of ATC, including chemotherapy, differentiation therapy, radioiodine therapy, gene therapy, targeted therapy, photothermal therapy, and combination therapy. Furthermore, potential future challenges and opportunities for the currently developed nanomedicines for ATC treatment are discussed. As far as we know, there are few reviews focusing on the nanomedicine of ATC therapy, and it is believed that this review will generate widespread interest from researchers in a variety of fields to further expedite preclinical research and clinical translation of ATC nanomedicines.

Visualizing γδ T cells by very late antigen-4-targeted positron emission tomography.

PURPOSE: γδ T cell-based immunotherapy has been rolled out as a promising treatment strategy for malignant tumors due to their potent anti-tumor cytotoxicity, ease of expansion, and unrestricted MHC feature. However, the dynamics and outcomes of γδ T cells in tumor sites are poorly understood. Reported strategies rely on ex vivo biolabeling, significantly limiting the application of γδ T cell molecular imaging. Herein, we investigated whether VLA-4 (very late antigen-4), a crucial component in the effective trafficking of lymphocytes, could serve as a biomarker to non-invasively visualize γδ T cells. METHODS: VLA-4-targeted tracer, 68 Ga-LLP2A, was evaluated in MDA-MB-231- and A549-bearing mice with adoptive transfer of γδ T cells by longitudinal PET/CT imaging. Imaging data were verified by ex vivo biodistribution studies, and the co-localization of CD3 and VLA-4 was validated by immunohistochemistry studies. RESULTS: 68 Ga-LLP2A showed high specificity to VLA-4-expressing γδ T cells in both in vitro and tumor-bearing mice with adoptive transfer of γδ T cells. Longitudinal PET imaging of 68 Ga-LLP2A in tumor-bearing mice with adoptive transfer of γδ T cells showed an increasing tumor tracer uptake, revealing the tumor-specific homing of γδ T cells. The presence of VLA-4-expressing γδ T cells in tumors was confirmed via histological analysis. CONCLUSION: To the best of our knowledge, we reported the first molecular probe, 68 Ga-LLP2A, for in vivo imaging of γδ T cells in live tumors, which advances PET imaging of γδ T cells and supports the translation of imaging agents for immunotherapeutic monitoring.

Visualizing Cytokeratin-14 Levels in Basal-Like Breast Cancer via ImmunoSPECT Imaging.

Cytokeratin-14 (CK14), also known as keratin 14, is mainly expressed in the basal layer of stratified squamous epithelium. It has a critical role in maintaining cell morphology and resisting external mechanical stress. High levels of CK14 have been found in multiple types of tumors, especially basal-like breast cancer (BLBC). In this study, an anti-CK14 monoclonal antibody was successfully produced, purified, and labeled with 99mTc to evaluate the feasibility of visualizing the CK14 level in BLBC. Higher CK14 levels were found in MDA-MB-468 cells and tumors compared with the levels in MDA-MB-231 cells and tumors as revealed by Western blotting and immunohistochemistry experiments. The high binding specificity of 99mTc-HYNIC-Anti-CK14 mAb to CK14+ BLBC cells was verified by cell uptake and blocking studies. Single-photon emission computed tomography (SPECT) images exhibited higher radioactivity accumulation in MDA-MB-468 tumors compared with MDA-MB-231 tumors. The signal in MDA-MB-468 tumors decreased significantly when 100-fold excess amounts of anti-CK14 mAb were injected 1 h prior to SPECT, further validating the high specificity of the tracer. Biodistribution study results were consistent with SPECT imaging. In conclusion, we successfully constructed a CK14 targeting tracer, 99mTc-HYNIC-Anti-CK14 mAb, which has a high binding ability to CK14+ tumors, signifying its potential value in the immunoSPECT imaging of BLBC.

Development of a triazolobenzodiazepine-based PET probe for subtype-selective vasopressin 1A receptor imaging.

OBJECTIVES: To enable non-invasive real-time quantification of vasopressin 1A (V1A) receptors in peripheral organs, we sought to develop a suitable PET probe that would allow specific and selective V1A receptor imaging in vitro and in vivo. METHODS: We synthesized a high-affinity and -selectivity ligand, designated compound 17. The target structure was labeled with carbon-11 and tested for its utility as a V1A-targeted PET tracer by cell uptake studies, autoradiography, in vivo PET imaging and ex vivo biodistribution experiments. RESULTS: Compound 17 (PF-184563) and the respective precursor for radiolabeling were synthesized in an overall yield of 49% (over 7 steps) and 40% (over 8 steps), respectively. An inhibitory constant of 0.9 nM towards the V1A receptors was measured, while excellent selectivity over the related V1B, V2 and OT receptor (IC50 >10,000 nM) were obtained. Cell uptake studies revealed considerable V1A binding, which was significantly reduced in the presence of V1A antagonists. Conversely, there was no significant blockade in the presence of V1B and V2 antagonists. In vitro autoradiography and PET imaging studies in rodents indicated specific tracer binding mainly in the liver. Further, the pancreas, spleen and the heart exhibited specific binding of [11C]17 ([11C]PF-184563) by ex vivo biodistribution experiments. CONCLUSION: We have developed the first V1A-targeted PET ligand that is suitable for subtype-selective receptor imaging in peripheral organs including the liver, heart, pancreas and spleen. Our findings suggest that [11C]PF-184563 can be a valuable tool to study the role of V1A receptors in liver diseases, as well as in cardiovascular pathologies.

Synthesis and Preclinical Evaluation of a 68Ga-Radiolabeled Peptide Targeting Very Late Antigen-3 for PET Imaging of Pancreatic Cancer.

Pancreatic cancer is highly malignant and has a five-year survival rate of 5% due to an early lymph node, nerve, and vascular metastasis. Integrin α3ß1 (also called very late antigen-3, VLA-3) is overexpressed in many tumors and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we developed a 68Ga-radiolabeled peptide tracer targeting the α3 unit of VLA-3 and evaluated its potential application in positron emission computed tomography (PET) imaging of pancreatic cancer. NOTA-CK11 was prepared by solid-phase synthesis and successfully radiolabeled with 68Ga with greater than 99% radiochemical purity and a specific activity of 37 ± 5 MBq/nmol (n = 5). The expression level of integrin α3 in three human pancreatic cancer cells was evaluated with the order of SW1990, BXPC-3, and PANC-1 from high to low, while the expression level of integrin ß1 was relatively close. When SW1990 cells with the highest expression level of VLA-3 were stained with FITC-CK11, strong fluorescence was observed by flow cytometry and under a laser confocal microscope. However, no significant fluorescence was observed in the blocking group when treated with excessive CK11. 68Ga-NOTA-CK11 showed significant radioactivity accumulation in SW1990 cells and was blocked by CK11 successfully. Subsequent small-animal PET imaging and biodistribution studies in mice bearing SW1990 xenografts confirmed its high tumor uptake with a good tumor-to-blood ratio and tumor-to-muscle ratio (2.45 ± 0.31 and 3.65 ± 0.33, respectively) at 1 h post injection of the probe. In summary, we successfully developed a peptide-based imaging agent, 68Ga-NOTA-CK11, that showed a strong binding affinity with VLA-3 and good target specificity for SW1990 cells and xenografted pancreatic tumor, rending it a promising radiotracer for PET imaging of VLA-3 expression in pancreatic cancer.

Florescence Imaging Lung Cancer with a Small Molecule MHI-148.

MHI-148 is a type of heptamethine cyanine dye that can cross the cytoplasmic membrane of lung cancer cells. Here we tested the cytotoxic, in vivo imaging of MHI-148 in lung-cancer nude mice model. Ex vivo imaging was also been measured by testing the major tissue fluorescence intensity. And, the small molecular compound MHI-148 had low cytotoxicity which could be visualized at 1 h post-injection in tumor. From ex vivo fluorescence imaging, the tumor showed the highest uptake of MHI-148 among all the selected organs expect for the time point of 2 h. MHI-148 could be used for effective imaging in lung cancer tissue with good stability and specificity, which suggested that MHI-148 could be an effective tumor clinical imaging agent.

Al18 F labeled sulfonamide-conjugated positron emission tomography tracer in vivo tumor-targeted imaging.

An ideal positron emission tomography (PET) tracer should be highly extractable by the tumor tissue or organ that contains low toxicity and can provide high-resolution images in vivo. In this work, the aim was to evaluate the application of Al18 F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid containing sulfonamide group (18 F-Al-NOTA-SN) as a potential tumor-targeting signal-enhanced radioactive tracer in PET. SN as a tumor-targeting group was incorporated to NOTA to make a ligand. Subsequently, this ligand reacted with Na18 F and AlCl3 to produce a compound 18 F-Al-NOTA-SN. This compound was further characterized and its property in regard to cell cytotoxicity assay, microPET imaging, biodistribution, cell uptake assay, and tumor selectivity in vitro and in vivo, was also investigated. 18 F-Al-NOTA-SN possessed low cell cytotoxicity and uptake to COS-7 and 293T healthy cells and high cell cytotoxicity and uptake to MDA-MB-231, HepG2, and HeLa tumor cells in vitro. Moreover, 18 F-Al-NOTA-SN showed good tumor-targeting property and high PET signal enhancement of HeLa tumors, liver, and kidneys in mice, as well as the uptake ratios of tumor to blood and tumor to muscle, were 4.98 and 3.87, respectively. 18 F-Al-NOTA-SN can be accepted to be kidney and liver eliminated earlier and show a potential tumor-targeting signal-enhanced radioactive tracer in PET.

Cell adhesion-related gene somatic mutations are enriched in aggressive papillary thyroid microcarcinomas.

BACKGROUND: Approximately half of the documented increases in differentiated thyroid carcinoma is due to identification of papillary thyroid microcarcinomas (PTMCs). Knowing whether PTMC is aggressive is required for proper treatment, but until now, there has been no method for assessing these traits and understanding the underlying mechanisms for aggressiveness. METHODS: We performed whole-exome sequencing of 16 PTMCs and matched normal thyroid tissues and GO/KEGG analysis to study genetic alterations and biological consequences associated with aggressive PTMCs, and then sequenced these genes using a next-generation gene-panel approach in an additional 70 PTMC samples including aggressive (n = 50) and non-aggressive (n = 20) groups. RESULTS: We identified 254 somatic mutations of 234 genes, for which 178 mutations in 168 genes were found in the aggressive group, and 76 mutations in 74 genes were found in the non-aggressive group. Several recurrent mutations in BRAF, VCAN, ALDH1L1, and MUC5B were identified, and many novel but infrequent mutations in other genes were also found. The aggressive cohort had more mutational burdens than the non-aggressive group (P = 0.004). Nonsynonymous mutations of 13 genes (MUC5B, TNN, SSPO, PPFIA1, PCDHGA2, ITGA8, ITGA4, DCHS1, CRNN, ROCK1, RELN, LAMC2, and AEBP1) were involved in cell adhesion, and these were only present in the aggressive group. Targeted sequencing of these genes revealed significant enrichment in the aggressive group (P = 0.000004). CONCLUSION: PTC may have evolved from PTMC due to sharing similar gene mutations, and the accumulation of such mutations promoted the aggressiveness of PTMC. Gene mutants associated with cell adhesion may be used to predict PTMC aggressiveness and allow more selective treatment.

Parathyroid cysts: experience of a rare phenomenon at a single institution.

BACKGROUND: Parathyroid cysts are relatively uncommon lesions and are often misdiagnosed. We evaluate our experience in the diagnosis of and therapy to correct parathyroid cystic lesions. METHODS: We retrospectively reviewed a series of 32 patients with parathyroid cysts who were admitted to our department between July 2011 and November 2016. Clinical pathological features of the patients, including age, gender, location, size, ultrasonography, histopathology, surgery, and follow-up, were analyzed. RESULTS: There were 22 female and 10 male participants with a median age of 46.7 years old (27-76 years old). Only two cysts were found in the superior mediastinum. The rest were located under the lower pole of the thyroid. All of the patients underwent ultrasonography scans and serum parathyroid hormone (PTH) assays. Three patients had elevated serum PTH levels, and they were further scanned with Tc99m sestamibi as functional cysts. In 29 cases of nonfunctional cysts, 3 cases were preoperatively diagnosed by cystic aspiration with PTH detection. The rest were diagnosed by postoperative immunopathology. All of the patients underwent cystectomy, and 24 patients also underwent thyroidectomy. There was a significant difference in cyst diameter size between the cystectomy alone and cystectomy with thyroidectomy groups (4.0 ± 2.0 vs 1.5 ± 1.0 cm; p < 0.05). No participant experienced recurrence during the median 36 months of follow-up. CONCLUSIONS: Cystic lesions located under the lower pole of the thyroid gland should be considered to have originated at the parathyroid gland. Cystic aspiration with PTH detection or postoperative immunopathology can lead to a definitive diagnosis. Cystectomy is still a commonly used and effective treatment.

Cell and gene therapy with reporter gene imaging in myocardial ischemia.

OBJECTIVE: Reporter gene/probe systems have proved to be reliable for monitoring gene/cell therapy. We sought to evaluate whether a reporter gene/probe system, namely the human estrogen receptor ligand binding domain (hERL)/16α-18F fluoro-17ß-estradiol (18F-FES), could be used for monitoring vascular endothelial growth factor (VEGF) gene expression and response to bone marrow mesenchymal stem cell (MSCs) therapy in ischemic heart disease. ANIMALS AND METHODS: Reporter gene hERL and therapeutic gene VEGF165 were linked through internal ribosome entry site (IRES), and then the recombinant adenovirus vector Adenovirus 5-hERL-IRES-VEGF (Ad5-EIV) was constructed and transfected into MSCs, and named Ad5-EIV-MSCs. Rat myocardial infarction was induced by coronary arterial branch ligature, and Ad5-EIV-MSCs were transplanted by injection into the peripheral myocardium, while non-transfected MSCs transplantation used as controls. Fluorine-18-FDG micro-PET imaging was performed to confirm myocardial infarction 1 day after surgery. Fluorine-18-FES micro-PET/CT images were acquired 2 days after Ad5-EIV-MSCs transplantation. Myocardial specimens were obtained and stained with hematoxylin-eosin (H&E) staining to verify the myocardial infarction. The expression of estrogen receptor (ER) and VEGF was detected using immunohistochemistry (IHC). RESULTS: Rat myocardial infarction models were successfully produced and confirmed by H&E staining. Images of 18F-FDG PET showed obvious reduced or absent uptake of 18F-FDG on the infarct myocardium, while uniform and well-distribution on the normal myocardium. 18F-FES micro-PET/CT showed the tracer notable accumulated in the apical region where Ad5-EIV-MSCs were injected with an uptake value of 0.38±0.09%ID/g, which was much higher than that of surrounding normal myocardium with nearly no uptake of 18F-FES (0.10±0.03%ID/g, n=5, P<0.05). In the group of non-transfected MSCs, the apical uptake was similar to that of normal myocardium. Immunohistochemistry studies demonstrated positive expression of both ER and VEGF in the involved region accompanied by active angiogenesis. CONCLUSION: This study confirmed that hERL/18F-FES could be used as a reporter gene/probe system for monitoring gene and cell therapy in the ischemic heart disease.

Semi-quantitative assessment of pulmonary arterial hypertension associated with congenital heart disease through myocardial perfusion imaging.

OBJECTIVE: The study aimed to use myocardial perfusion imaging (MPI) as a semi-quantitative method to assess the clinical severity of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD). SUBJECTS AND METHODS: A total of 24 patients with PAH related to CHD (PAH-CHD) who received interventional or medical treatment were included. All patients underwent physical examination, cardiac function evaluation, biochemical test, echocardiography, right heart catheterization (RHC), and MPI with 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) pre and 6 months post treatments. The correlation between MPI target/background (T/B) ratios and other variables were calculated. The receiver operating characteristic (ROC) curves were developed to evaluate the diagnostic value of T/B ratios. RESULTS: Most of the cardiac functional parameters, surplus pulse O2 (SPO2), biochemical values and right heart catheterization parameters were found significantly elevated after treatment (P<0.05). Pre-treatment MPI showed that T/B ratio had strong correlations with SPO2, Borg scale, cardiac output (CO), cardiac index (CI), right ventricular stroke volume (RV-SV), pulmonary artery pressure (PAP), total pulmonary resistance (TPR), total pulmonary resistance index (TPRI), pulmonary vascular resistance (PVR), and pulmonary vascular resistance index (PVRI). After 6 months treatment, the correlation between T/B ratios and most of these parameters measured were reduced. Receiver operating characteristics curves showed that the diagnostic performance of MPI T/B ratio in moderate/severe PAH patients was significant. The area under the curve (AUC) when measured pre-treatment was 0.929 (P=0.002) and reduced to 0.800 (P=0.046) at post-treatment. CONCLUSION: Semi-quantitative MPI has high diagnostic value in evaluating the severity level of pulmonary arterial hypertension in patients with congenital heart disease. The diagnostic performance of MPI at pre-treatment patients was superior to that at post-treatment. More cases need to be included for further study.

Imaging malignant melanoma with (18)F-5-FPN.

PURPOSE: Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. (18)F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ((18)F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. METHODS: (18)F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using (18)F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with (18)F-FDG. PET imaging with (18)F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. RESULTS: (18)F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of (18)F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. (18)F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. (18)F-5-FPN and (18)F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of (18)F-5-FPN was ten times higher than that of (18)F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). (18)F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. CONCLUSION: (18)F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity and favourable pharmacokinetics. (18)F-5-FPN may be an ideal molecular probe for melanoma diagnosis and staging.

(99m) Tc-labeled tetramer and pentamer of single-domain antibody for targeting epidermal growth factor receptor in xenografted tumors.

The single-domain antibody EG2 can be fused with right-handed coiled-coil (RHCC) and human cartilage oligomeric matrix protein (COMP), to form the multivalent antibodies EG2-RHCC and EG2-COMP. We labeled these two antibodies with (99m) Tc and assessed their targeting efficiency for epidermal growth factor receptor (EGFR). Cell binding, uptake, efflux, and blocking studies were performed with EGFR high- and/or low-expressing cells with (99m) Tc-labeled EG2-RHCC or EG2-COMP. Single photon-emission computed tomography (SPECT) imaging and biodistribution studies were further carried out. Both (99m) Tc-EG2-RHCC and (99m) Tc-EG2-COMP can specially bind to EGFR in vitro. SPECT imaging showed that A431, which expresses high levels of EGFR, was clearly visible 6 h after (99m) Tc-EG2-COMP injection; however, it was not detectable after administration of (99m) Tc-EG2-RHCC. Uptake of both antibodies by the non-EGFR-secreting OCM-1 tumors was low. EG2-COMP shows promise in identifying EGFR over-expression in tumors; however, EG2-RHCC may not be suitable for targeting EGFR in vivo.

Unusual Achalasia Presentation Detected on 131I SPECT/CT in a Papillary Thyroid Carcinoma Patient.

ABSTRACT: Various factors leading to unexpected false-positive 131I uptake have been extensively studied in patients with differentiated thyroid carcinoma. In this case, we present a patient who underwent achalasia surgery and subsequently exhibited abnormal 131I uptake on SPECT/CT imaging. The patient was a known case of papillary thyroid carcinoma that suggested to 131I therapy. 131I SPECT/CT showed linear increased activity in the distended esophagus.

Photothermal therapy: a novel potential treatment for prostate cancer.

Prostate cancer (PCa) is a leading cause of cancer-related death in men, and most PCa patients treated with androgen deprivation therapy will progress to metastatic castration-resistant prostate cancer (mCRPC) due to the lack of efficient treatment. Recently, lots of research indicated that photothermal therapy (PTT) was a promising alternative that provided an accurate and efficient prostate cancer therapy. A photothermic agent (PTA) is a basic component of PPT and is divided into organic and inorganic PTAs. Besides, the combination of PTT and other therapies, such as photodynamic therapy (PDT), immunotherapy (IT), chemotherapy (CT), etc., provides an more efficient strategy for PCa therapy. Here, we introduce basic information about PTT and summarize the PTT treatment strategies for prostate cancer. Based on recent works, we think the combination of PPT and other therapies provides a novel possibility for PCa, especially CRPC clinical treatment.

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.