A poor prognostic male choriocarcinoma with multiple systemic metastases: a case report and the literature review.

Background: Non-gestational choriocarcinoma, also known as primary choriocarcinoma, is extremely rare in men, manifesting with specific signs such as breast feminization, testicular atrophy, and loss of libido. The presentation typically includes elevated serum ß-hCG levels, widespread metastatic disease, and a rapid progression of the condition. Case report: We present a rare case of a 41-year-old man diagnosed with choriocarcinoma, exhibiting a unique combination of multiple metastases, including lung, brain, bone, and retroperitoneal lymph node metastases, as confirmed by 18F-FDG PET/CT imaging. The patient was treated with aggressive chemotherapy and pembrolizumab, and the prognosis remained poor. The patient's overall survival was a mere 5 months following diagnosis. Conclusion: Non-gestational choriocarcinoma represents a rare entity in clinical practice and should be considered in young men presenting with gynaecomastia and elevated ß-hCG levels alongside normal gonads. Thus, we advocate for a more comprehensive inquiry into medical history and a systematic examination. The 18F-FDG PET/CT examination not only visually delineates the lesion's location and extent but also serves as a cornerstone for clinical tumor staging, providing valuable support for treatment monitoring and subsequent follow-up.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

A rare case of primary cardiac diffuse large B-cell lymphoma imaged with 18F-FDG PET/CT: a case report and literature review.

Background: One of the exceptionally rare forms of non-Hodgkin's lymphoma (NHL) is primary cardiac lymphoma (PCL). The principal clinical manifestation in patients with PCL involves cardiac symptoms resulting from myocardial infiltration by lymphoma, including arrhythmias, heart failure, and chest pain. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for assessing clinically staging NHL. Case report: We present a rare case involving a 72-year-old woman diagnosed with primary intracardiac diffuse large B-cell lymphoma. For further staging, the patient underwent 18F-FDG PET/CT, revealing multiple nodular soft tissue density lesions in the heart and pericardium exhibiting increased FDG metabolism (SUVmax = 12.1). The supradiaphragmatic and infradiaphragmatic segments of the inferior vena cava exhibited irregular morphology with localized nodular changes and increased FDG metabolism in the surrounding area (SUVmax = 9.7). Additionally, multiple enlarged lymph nodes were identified in the left axilla, mediastinum, and adjacent to the abdominal aorta, displaying heterogeneous FDG uptake with an SUVmax of 9.3, indicating lymphoma involvement. The above imaging findings suggested that the mass was a PCL. Hence, the patient underwent a combination of chemotherapy and immunotherapy using R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone). Following two courses of treatment within a span of 2 months, there was a partial remission observed in the cardiac lymphoma and the enlarged lymph nodes. Conclusion: The case elucidated in this report contributes to an enhanced understanding of the disease for clinicians, with 18F-FDG PET/CT providing comprehensive insights into the extent of cardiac involvement, as well as the engagement of extracardiac organs and pathologic lymph nodes. The 18F-FDG PET/CT examination not only visually delineates the lesion's location and extent but also serves as a cornerstone for clinical tumor staging, offering valuable support for treatment monitoring and subsequent follow-up.

Molecular Imaging of Fibrosis in Benign Diseases: An Overview of the State of the Art.

Fibrosis is a progressive pathological process participating in the progression of many diseases and can ultimately result in organ malfunction and failure. Around 45% of deaths in the United States are believed to be attributable to fibrotic disorders, and there are no favorable treatment regiments available to meet the need of blocking fibrogenesis, reversing established fibrosis, and curing diseases, especially in the terminal stage. Therefore, early detection and continuous monitoring provide valuable benefits for patients. Among all the advanced techniques developed in recent years for fibrosis evaluation, molecular imaging stands out with its distinct advantage of visualizing biochemical processes and patterns of target localization at the molecular and cellular level. In this review, we summarize the current state of the art in molecular imaging of benign fibrosis diseases. We will first introduce molecular pathways underlying fibrosis processes and potential targets. We will then elaborate on molecular probes that have been developed thus far, expounding on their mechanisms and current states of translational advancement. Finally, we will delineate the extant challenges impeding further progress in this area and the prospective benefits after overcoming these problems.

Minocycline-loaded nHAP/PLGA microspheres for prevention of injury-related corneal angiogenesis.

BACKGROUND: Corneal neovascularization (CoNV) threatens vision by disrupting corneal avascularity, however, current treatments, including pharmacotherapy and surgery, are hindered by limitations in efficacy and adverse effects. Minocycline, known for its anti-inflammatory properties, could suppress CoNV but faces challenges in effective delivery due to the cornea's unique structure. Therefore, in this study a novel drug delivery system using minocycline-loaded nano-hydroxyapatite/poly (lactic-co-glycolic acid) (nHAP/PLGA) nanoparticles was developed to improve treatment outcomes for CoNV. RESULTS: Ultra-small nHAP was synthesized using high gravity technology, then encapsulated in PLGA by a double emulsion method to form nHAP/PLGA microspheres, attenuating the acidic by-products of PLGA degradation. The MINO@PLGA nanocomplex, featuring sustained release and permeation properties, demonstrated an efficient delivery system for minocycline that significantly inhibited the CoNV area in an alkali-burn model without exhibiting apparent cytotoxicity. On day 14, the in vivo microscope examination and ex vivo CD31 staining corroborated the inhibition of neovascularization, with the significantly smaller CoNV area (29.40% ± 6.55%) in the MINO@PLGA Tid group (three times daily) than that of the control group (86.81% ± 15.71%), the MINO group (72.42% ± 30.15%), and the PLGA group (86.87% ± 14.94%) (p < 0.05). Fluorescein sodium staining show MINO@PLGA treatments, administered once daily (Qd) and three times daily (Tid) demonstrated rapid corneal epithelial healing while the Alkali injury group and the DEX group showed longer healing times (p < 0.05). Additionally, compared to the control group, treatments with dexamethasone, MINO, and MINO@PLGA were associated with an increased expression of TGF-ß as evidenced by immunofluorescence, while the levels of pro-inflammatory cytokines IL-1ß and TNF-α demonstrated a significant decrease following alkali burn. Safety evaluations, including assessments of renal and hepatic biomarkers, along with H&E staining of major organs, revealed no significant cytotoxicity of the MINO@PLGA nanocomplex in vivo. CONCLUSIONS: The novel MINO@PLGA nanocomplex, comprising minocycline-loaded nHAP/PLGA microspheres, has shown a substantial capacity for preventing CoNV. This study confirms the complex's ability to downregulate inflammatory pathways, significantly reducing CoNV with minimal cytotoxicity and high biosafety in vivo. Given these findings, MINO@PLGA stands as a highly promising candidate for ocular conditions characterized by CoNV.

Predicting microvascular invasion in small (≤ 5 cm) hepatocellular carcinomas using radiomics-based peritumoral analysis.

OBJECTIVE: We assessed the predictive capacity of computed tomography (CT)-enhanced radiomics models in determining microvascular invasion (MVI) for isolated hepatocellular carcinoma (HCC) ≤ 5 cm within peritumoral margins of 5 and 10 mm. METHODS: Radiomics software was used for feature extraction. We used the least absolute shrinkage and selection operator (LASSO) algorithm to establish an effective model to predict patients' preoperative MVI status. RESULTS: The area under the curve (AUC) values in the validation sets for the 5- and 10-mm radiomics models concerning arterial tumors were 0.759 and 0.637, respectively. In the portal vein phase, they were 0.626 and 0.693, respectively. Additionally, the combined radiomics model for arterial tumors and the peritumoral 5-mm margin had an AUC value of 0.820. The decision curve showed that the combined tumor and peritumoral radiomics model exhibited a somewhat superior benefit compared to the traditional model, while the fusion model demonstrated an even greater advantage, indicating its significant potential in clinical application. CONCLUSION: The 5-mm peritumoral arterial model had superior accuracy and sensitivity in predicting MVI. Moreover, the combined tumor and peritumoral radiomics model outperformed both the individual tumor and peritumoral radiomics models. The most effective combination was the arterial phase tumor and peritumor 5-mm margin combination. Using a fusion model that integrates tumor and peritumoral radiomics and clinical data can aid in the preoperative diagnosis of the MVI of isolated HCC ≤ 5 cm, indicating considerable practical value. CRITICAL RELEVANCE STATEMENT: The radiomics model including a 5-mm peritumoral expansion is a promising noninvasive biomarker for preoperatively predicting microvascular invasion in patients diagnosed with a solitary HCC ≤ 5 cm. KEY POINTS: • Radiomics features extracted at a 5-mm distance from the tumor could better predict hepatocellular carcinoma microvascular invasion. • Peritumoral radiomics can be used to capture tumor heterogeneity and predict microvascular invasion. • This radiomics model stands as a promising noninvasive biomarker for preoperatively predicting MVI in individuals.

Immune cholangitis related to anti-programmed cell death and programmed cell death ligand agents for the treatment of intrahepatic cholangiocarcinoma.

Anti-programmed cell death (anti-PD1) and anti-programmed cell death ligand (anti-PDL1) agents represent a burgeoning field of immunotherapy with an expanding array of indications. In this report, we present the observation of a patient with intrahepatic cholangiocarcinoma exhibiting features of immune-related cholangitis.

Deep Learning Radiomics Analysis of CT Imaging for Differentiating Between Crohn's Disease and Intestinal Tuberculosis.

This study aimed to develop and evaluate a CT-based deep learning radiomics model for differentiating between Crohn's disease (CD) and intestinal tuberculosis (ITB). A total of 330 patients with pathologically confirmed as CD or ITB from the First Affiliated Hospital of Zhengzhou University were divided into the validation dataset one (CD: 167; ITB: 57) and validation dataset two (CD: 78; ITB: 28). Based on the validation dataset one, the synthetic minority oversampling technique (SMOTE) was adopted to create balanced dataset as training data for feature selection and model construction. The handcrafted and deep learning (DL) radiomics features were extracted from the arterial and venous phases images, respectively. The interobserver consistency analysis, Spearman's correlation, univariate analysis, and the least absolute shrinkage and selection operator (LASSO) regression were used to select features. Based on extracted multi-phase radiomics features, six logistic regression models were finally constructed. The diagnostic performances of different models were compared using ROC analysis and Delong test. The arterial-venous combined deep learning radiomics model for differentiating between CD and ITB showed a high prediction quality with AUCs of 0.885, 0.877, and 0.800 in SMOTE dataset, validation dataset one, and validation dataset two, respectively. Moreover, the deep learning radiomics model outperformed the handcrafted radiomics model in same phase images. In validation dataset one, the Delong test results indicated that there was a significant difference in the AUC of the arterial models (p = 0.037), while not in venous and arterial-venous combined models (p = 0.398 and p = 0.265) as comparing deep learning radiomics models and handcrafted radiomics models. In our study, the arterial-venous combined model based on deep learning radiomics analysis exhibited good performance in differentiating between CD and ITB.

An elderly low-grade fibromyxoid sarcoma patient with early postoperative recurrences and metastases: a case report and literature review.

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of soft tissue sarcoma that often involves the deep soft tissue of the extremities and trunk in young and middle-aged adults. It is uncommon in the elderly. Here we discuss a case of LGFMS in an elderly patient who had recurrence and metastasis within 2 years of resection of the primary tumor. Case report: A 71-year-old LGFMS patient was presented with a mass in the left forearm accompanied by pain and numbness from the left upper arm to fingers. The patient subsequently underwent 3 surgical resections, although she had 3 recurrences within 6 months after the initial diagnosis. Considering the malignant biological behavior of the tumor, an amputation at 5 cm above the elbow was eventually performed. However, recurrence in the extremity of the stump and chest wall metastasis were observed 2 years after amputation. Then resection of the metastases, radiotherapy and particle implantation therapy were performed. The patient is currently undergoing follow-up and has no evidence of recurrence. Conclusion: In our case, multiple early postoperative recurrences may be associated with a positive margin at initial operation. The patient underwent a total of 5 operations including local resection of the primary tumor, twice wide resections, amputation and metastatic surgery with 4 early postoperative recurrences and metastases within 4 years, suggesting that LGFMS may have highly invasive biological behavior. Our case demonstrated that early aggressive surgical treatment is recommended for LGFMS patients with a positive margin at initial operation and patients who had recurrence even after wide resection rather than local resection. Further research is needed to develop more effective treatment options for rapidly progress and highly aggressive LGFMS.

Esophago-pulmonary artery fistula caused by fish bone impaction.

We present a case of a 65-year-old male who experienced posterior sternal pain, accompanied by a week-long fever following the consumption of fish. Computed tomography (CT) examination revealed a fish bone in the middle esophageal, along with a small amount of gas in the mediastinum. A focal pseudoaneurysm formation was observed in the posterior wall of the left pulmonary artery trunk, accompanied by the presence of gas and septic emboli in the main trunk of the left pulmonary artery and some of its branches. Furthermore, distal pulmonary tissue infarction with associated infection was observed (Figure 1A-F). Clinical diagnosis: Esophago-pulmonary artery fistula caused by fish bone impaction. Reports of esophago-pulmonary artery fistulas without involvement of the trachea or bronchi are rare.

Gastric mucormycosis presenting as diffuse thickening of the gastric wall with enhancement

We report the case of a 63-year-old woman who presented with abdominal distension and pain two months ago, which worsened after eating. An abdominal CT examination revealed uneven thickening of the gastric wall on the greater curvature side of the gastric body, with progressive obviously enhancement. She was then examined by an upper endoscopy, which showed mucosal swelling on the greater curvature side of the lower gastric body with exudation of necrotic materials. Biopsies of the lesion were taken and histological results revealed a large number of broad-based and non-septate hyphae, with positive expression of PAS (Periodic Acid-Schiff) and hexamine silver stains, The patient was treated with amphotericin B liposomal antifungal therapy and remained under surveillance for six months without evidence of disease progression by follow-up upper endoscopy. (AU)

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

CD146-targeted nuclear medicine imaging in cancer: state of the art.

The transmembrane glycoprotein adhesion molecule CD146 is overexpressed in a wide variety of cancers. Through molecular imaging, a specific biomarker's expression and distribution can be viewed in vivo non-invasively. Radionuclide-labeled monoclonal antibodies or relevant fragments that target CD146 may find potential applications in cancer imaging, thereby offering tremendous value in cancer diagnosis, staging, prognosis evaluation, and prediction of drug resistance. This review discusses the recent developments of CD146-targeted molecular imaging via nuclear medicine, especially in malignant melanoma, brain tumor, lung cancer, liver cancer, breast cancer, and pancreatic cancer. Many studies have proved that CD146 targeting may present a promising strategy for cancer theranostics.

Case Report: A rare case of multicentric angiosarcomas of bone mimicking multiple myeloma on 18F-FDG PET/CT.

Background: Angiosarcoma, a rare endothelial-origin tumor, can develop throughout the body, with the head and neck skin being the most commonly affected areas. It can also originate in other sites such as the breast, iliac artery, and visceral organs including the liver, spleen, and kidneys. Angiosarcoma of the bone is remarkably rare, presenting as either unifocal or multifocal bone lesions and often leading to a grim prognosis. Diagnosing bone angiosarcoma poses a significant challenge. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for evaluating distant metastases and clinically staging angiosarcomas. Case report: A 57-year-old woman presented with a 10-day history of dizziness and headaches. Cranial CT scan revealed bone destruction of the parietal bone, accompanied by soft tissue lesions, protruding into the epidural space. MRI examination demonstrated lesions with slightly elevated signal intensity on T2FLAIR, showing moderate enhancement. Furthermore, multiple foci were observed within the T12, L1-5, and S1-2 vertebrae, as well as in the bilateral iliac bones. For staging, 18F-FDG PET/CT was performed. The MIP PET showed multifocal FDG-avid lesions in the sternum, bilateral clavicles, bilateral scapulae, multiple ribs, and pelvic bones. Heterogeneous FDG uptake was observed in multiple bone lesions, including intracranial (SUVmax = 11.3), right transverse process of the T10 vertebra (SUVmax = 5.8), ilium (SUVmax = 3.3), and pubis (SUVmax = 4.7). The patient underwent surgical resection of the cranial lesion. The pathological diagnosis was made with a highly differentiated angiosarcoma. Conclusion: Angiosarcoma of bone on FDG PET/CT scans is characterized by abnormal FDG uptake along with osteolytic destruction. This case highlights that angiosarcoma of bone can manifest as multicentric FDG uptake, resembling the pattern seen in multiple myeloma. FDG PET/CT can be a useful tool for staging this rare malignant tumor, offering the potential to guide biopsy procedures toward the most metabolically active site. And it should be considered in the differential diagnosis of multiple osteolytic lesions, including metastatic carcinoma, multiple myeloma, and lymphoma of bone.