Augmentation of Radioiodine Uptake by Pulmonary Metastasis of Papillary Thyroid Carcinoma Treated with Dabrafenib and Trametinib.

Redifferentiation therapy with Dabrafenib (a BRAF inhibitor) and Trametinib (a MEK inhibitor) restores radioiodine avidity of radioiodine-refractory papillary thyroid carcinoma (PTC). A 50-year-old man was diagnosed with radioiodine-refractory PTC pulmonary metastasis post prior total thyroidectomy and radioiodine ablation. The patient was treated with Dabrafenib and Trametinib, followed by second radioiodine ablation with I-131 sodium iodine. Diffuse increased radioiodine uptake by pulmonary metastasis was visualized on post ablation whole body scan. Response to second radioiodine ablation was demonstrated by decrease in size of pulmonary nodules seen on chest CT, along with decrease of thyroglobulin level.

An image inpainting-based data augmentation method for improved sclerosed glomerular identification performance with the segmentation model EfficientNetB3-Unet.

The percent global glomerulosclerosis is a key factor in determining the outcome of renal transfer surgery. At present, the rate is typically computed by pathologists, which is labour intensive and nonstandardized. With the development of Deep Learning (DL), DL-based segmentation models can be used to better identify and segment normal and sclerosed glomeruli. Based on this, we can better quantify percent global glomerulosclerosis to reduce the discard rate of donor kidneys. We used 51 whole slide images (WSIs) from different institutions that are publicly available on the internet. However, the number of sclerosed glomeruli is much smaller than that of normal glomeruli in different WSIs, which can reduce the effectiveness of Deep Learning. For better sclerosed glomerular identification and segmentation performance, we modified and trained a GAN (generative adversarial network)-based image inpainting model to obtain more synthetic sclerosed glomeruli. Our proposed inpainting method achieved an average SSIM (Structural Similarity) of 0.8086 and an average PSNR (Peak Signal-to-Noise Ratio) of 22.8943 dB in the area of generated sclerosed glomeruli. We obtained sclerosed glomerular segmentation performance improvement by adding synthetic sclerosed glomerular images and achieved the best Dice of glomerular segmentation in different test sets based on the modified Unet model.

Recent Advances in Cancer Imaging with 64CuCl2 PET/CT.

Copper is required for cancer cell proliferation and tumor angiogenesis. Radioactive copper-64 chloride (64CuCl2) is a useful radiotracer for cancer imaging with position emission tomography (PET) based on increased cellular uptake of copper mediated by human copper transporter 1 (hCtr1) expressed on cancer cell membrane. Significant progress has been made in research of using 64CuCl2 as a radiotracer for cancer imaging with PET. Radiation dosimetry study in humans demonstrated radiation safety of 64CuCl2. Recently, 64CuCl2 was successfully used for PET imaging of prostate cancer, bladder cancer, glioblastoma multiforme (GBM), and non-small cell lung carcinoma in humans. Based on the findings from the preclinical research studies, 64CuCl2 PET/CT also holds potential for diagnostic imaging of human hepatocellular carcinoma (HCC), malignant melanoma, and detection of intracranial metastasis of copper-avid tumors based on low physiological background of radioactive copper uptake in the brain. Copper-64 radionuclide emits both ß+ and ß- particles, suggesting therapeutic potential of 64CuCl2 for radionuclide cancer therapy of copper-avid tumors. Recent progress in production of therapeutic copper-67 radionuclide invites clinical research in use of theranostic pair of 64CuCl2 and 67CuCl2 for cancer imaging and radionuclide therapy.

FDG PET/CT findings and post-treatment changes of COVID-19 pneumonia in a patient with lymphoma: A case report.

A 29-year-old male with a history of Hodgkin's lymphoma presented for evaluation of response to chemotherapy with positron emission tomography/computed tomography using fluorine-18-fluoro-2-deoxy-d-glucose (18F-FDG PET/CT). Follow-up 18F-FDG PET/CT imaging demonstrated resolution of previously noted FDG avid axillary lymphadenopathy. However, multiple opacities with increased FDG uptake were noted in the lungs bilaterally, which were suspicious for pulmonary infection, including viral pneumonia. The patient tested positive for coronavirus disease 2019 (COVID-19) virus infection by reverse transcription-polymerase chain reaction (RT-PCR). Additional cycles of chemotherapy were delayed until the patient became negative for COVID-19 virus infection on follow-up RT-PCR test 2 weeks later. The patient received two additional cycles of chemotherapy. Follow-up 18F-FDG PET/CT post chemotherapy demonstrated a decrease in the size of the previously seen mediastinal lymphadenopathy, reduction of FDG uptake by the previously seen mediastinal lymphadenopathy, and reduction of FDG uptake by the previously seen pulmonary opacities, at 2 months after COVID-19 diagnosis. The findings of this case report demonstrated the importance of recognition of pulmonary abnormalities caused by COVID-19 pneumonia on 18F-FDG PET/CT imaging for clinical management of patients with lymphoma.

Reduction in Copper Uptake and Inhibition of Prostate Cancer Cell Proliferation by Novel Steroid-based Compounds.

BACKGROUND/AIM: Knockdown of human copper transporter 1 has been associated with reduction in copper uptake and suppression of prostate cancer cell proliferation and tumor growth. This study evaluated the effects of steroid-based compounds on copper uptake and proliferation of prostate cancer cells based on their anticancer activity and previous docking analysis of steroid-based copper transporter 1 inhibitors. MATERIALS AND METHODS: We synthesized several new steroid-based compounds and used 64Cu uptake assay and copper quantification assay with inductively coupled plasma mass spectrometry to study their effects on the cellular copper uptake by prostate cancer cells. Additionally, we used CCK-8 cell proliferation assay to study their effects on the proliferation of prostate cancer cells. RESULTS: Significant reduction in cellular copper uptake was observed in the prostate cancer cells treated with these new steroid-based compounds. Moreover, proliferation of prostate cancer cells was suppressed by treatment with the steroid-based compound 6, which had the strongest copper uptake inhibition activity. CONCLUSION: Reduction in copper uptake and inhibition of cell proliferation were demonstrated in prostate cancer cells treated with the new steroid-based compounds synthesized in this study. Steroid-based copper transporter 1 inhibitors may become novel anticancer drugs for targeted anti-copper therapy of prostate cancer and other copper hypermetabolic cancers.

Isolated Hepatic Metastasis of Prostate Cancer with Variable 18F-fluociclovine Uptake by PET/CT Imaging.

A 74-year-old man presented with rapid rising prostate-specific antigen (PSA) 2 years after treatment of prostate cancer with prostatectomy and salvage radiation therapy. PSA increased from 923 to 4349 ng/mL within 2 months. No osseous metastatic lesions of prostate cancer were detected by 18F-sodium fluoride PET/CT imaging at an outside facility. 18F-fluciclovine PET/CT imaging was performed to evaluate local recurrence of prostate cancer at surgical bed of prostatectomy and distant metastasis. One small focus of low-level 18F-fluciclovine radiotracer uptake was noted in the surgical bed of prostatectomy without corresponding soft tissue mass on CT. No fluciclovine-avid lymph nodes or osseous metastatic lesions were detected, but multiple hypodense lesions of variable 18F-fluciclovine radiotracer uptake were noted in the liver, concerning for isolated liver metastasis of prostate cancer. The patient underwent docetaxel chemotherapy for treatment of prostate cancer liver metastasis and showed a favorable response to treatment by significant decreased size of the hypodense lesions in the liver on post treatment abdominal CT, along with dramatic reduction of PSA level and improvement of liver function. The findings from this case highlight the importance of checking hypoattenuating lesions in the liver for the presence of prostate cancer metastatic lesions that might appear similar to other benign hypoattenuating lesions of low fluciclovine uptake relative to physiological 18F-fluciclovine uptake in the normal liver tissues, a potential pitfall at interpretation of 18F-fluociclovine PET/CT imaging.

Prognostic value of metabolic tumor volume and total lesion glycolysis from ¹8F-FDG PET/CT in lymph node metastases and risk stratification of endometrial carcinoma.

OBJECTIVE: To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), measured by preoperative ¹8F-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG PET/CT), in risk stratification of patients with endometrial carcinoma (EC). METHODS: The patients with pathological diagnosis of EC who underwent preoperative ¹8F-FDG PET/CT imaging were retrospectively selected for analysis of the prognostic values of PET parameters in risk classification and lymph node metastases (LNMs). Receiver-operating-characteristic analysis was used to analyze the correlation of PET parameters cutoff values with deep myometrial invasion (MI), lymphovascular space involvement and LNM for prognostic values in risk stratification. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for detection of LNM are 83.3%, 99.7%, 90.9%, 99.5% and 99.2%, respectively. The MTV and TLG of primary lesion of EC in the patients with LNM are notably higher than those in patients without LNM, p<0.010. The MTV and TLG of the EC primary lesions in high-risk patients are significantly higher than those in low-risk patients (p<0.010), but the maximum standardized uptake value (SUVmax) is not. The MTV and TLG of primary lesions were superior to SUVmax for predicting of deep MI, LNM and high-risk of EC (p<0.005). CONCLUSION: MTV and TLG of primary lesions are more valuable in predicting risk stratification of EC patients. Preoperative ¹8F-FDG PET/CT imaging is useful in predicting the LNM of EC and may help guide pelvic lymphadenectomy to avoid unnecessary pelvic lymphadenectomy in EC patients with low-risk stratification.

Novel Meta-iodobenzylguanidine-Based Copper Thiosemicarbazide-1-guanidinomethylbenzyl Anticancer Compounds Targeting Norepinephrine Transporter in Neuroblastoma.

Meta-iodobenzylguanidine (MIBG) is a ligand with high affinity against norepinephrine transporter (NET) that has been used for diagnostic imaging and radionuclide therapy of NET-expressing tumors, such as neuroblastoma. We hypothesize that MIBG can be used as a ligand for development of new anticancer drugs targeting NET-expressing neuroblastoma (NB). To test our hypothesis, we synthesized two MIBG-based anticancer copper complexes [Cu(m-TSBG)2 and Cu(p-TSBG)2] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG)2 and Cu(p-TSBG)2 compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG)2 and Cu(p-TSBG)2 was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG)2 or Cu(p-TSBG)2 onto NET-expressing NB cells. Both Cu(m-TSBG)2 or Cu(p-TSBG)2 compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.

Anti-prostate cancer activity of 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide copper complexes in vivo by bioluminescence imaging.

Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide complex (CuHQTS) is a copper complex with strong anticancer activity against cisplatin-resistant neuroblastoma and prostate cancer cells in vitro by cell proliferation assay or fluorescent microscopic imaging. This study aimed to evaluate anti-prostate cancer activity of CuHQTS in vivo by bioluminescence imaging (BLI) and tumor size measurement, using athymic nu/nu mice implanted with prostate cancer cells carrying luciferase reporter gene (Luc-PC3). Growth of Luc-PC3 cells (1 × 105 cells) implanted in athymic nu/nu mice treated with CuHQTS for 2 weeks was suppressed by measurement of luciferase signals (6.18 × 107 to 5.36 × 107 p/s/cm2/sr) with BLI, compared with luciferase signals of Luc-PC3 cells (4.66 × 107 to 1.51 × 108 p/s/cm2/sr, p < 0.05) in the mice treated with normal saline of placebo control. Moreover, the size of PC-3 xenograft tumor (126.5 ± 34.2 mm3) in athymic nu/nu mice treated with CuHQTS was significantly smaller than the size of PC-3 xenograft tumor (218.6 ± 48.0 mm3, p < 0.05) in athymic nu/nu mice treated with normal saline of placebo control, suggesting in vivo tumor growth inhibition activity of CuHQTS on prostate cancer. The findings of this study support further investigation of CuHQTS as a promising new anticancer agent for the treatment of metastatic prostate cancer refractory to anticancer drugs currently available.

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

Aim: To synthesize and evaluate the imaging potential of Bom-PEG-[64Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. Materials & methods: [64Cu]CuS NPs were synthesized in aqueous solution by 64CuCl2 and Na2S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [64Cu]CuS NPs to produce Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Results: Bom-PEG-[64Cu]CuS and PEG-[64Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[64Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Conclusion: Radiolabeled Bom-PEG-[64Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

Anticancer Activity of Copper Complex of (4R)-(-)-2-Thioxo-4-thiazolidinecarboxylic Acid and 3-Rhodaninepropionic Acid on Prostate and Breast Cancer Cells by Fluorescent Microscopic Imaging.

Copper complexes with strong anticancer activity are promising new drugs for treatment of patients with metastatic cancer. Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide (CuHQTS) and copper 8-hydroxyquinoline-2-carboxaldehyde-4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) were found to have strong anticancer activity against cisplatin-resistant neuroblastoma cells and prostate cancer cells. This study aimed to synthesize and characterize two new anticancer copper complexes, copper complex of (4R)-(-)-2-Thioxo-4-thiazolidinecarboxylic acid (CuTTDC), and copper complex of 3-Rhodaninepropionic acid-copper complex (CuRDPA). Cell growth inhibition and cytotoxicity of CuTTDC and CuRDPA on prostate and breast cancer cells were evaluated with Cell Counting Kits-8 (CCK8) assay and fluorescent microscopic imaging respectively. Strong anticancer activity of CuTTDC and CuRDPA was demonstrated by growth inhibition and cytotoxicity of prostate and breast cancer cells treated with these two copper complexes, supporting further investigation of potential use of these two new anticancer complexes for treatment of prostate and breast cancer metastasis.

Anti-Prostate Cancer Activity of 8-Hydroxyquinoline-2-Carboxaldehyde-Thiosemicarbazide Copper Complexes by Fluorescent Microscopic Imaging.

Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide (CuHQTS) and copper 8-hydroxyquinoline-2-carboxaldehyde-4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) are two copper thiosemicarbazone complexes with potent anticancer activity on cisplatin-resistant neuroblastoma cells. This study aimed to evaluate anti-prostate cancer activity of these two copper complexes in vitro. Both CuHQTS and CuHQDMTS inhibited proliferation of prostate cancer cells and showed cytotoxicity on prostate cancer cells carrying green fluorescent protein (GFP) by fluorescent microscopic imaging. The findings of this study demonstrated anti-prostate cancer activity of CuHQTS and CuHQDMTS and suggested that GFP-carrying prostate cancer cells might be used for testing anticancer activity of copper complexes by fluorescent microscopic imaging.

Ectopic Thyroid Tissue in the Mediastinum Characterized by Histology and Functional Imaging with I-123 SPECT/CT.

Ectopic thyroid tissue is a rare entity and when discovered it is typically along the pathway of embryologic migration of the thyroid. We present a case of incidental finding of ectopic thyroid tissue within mediastinum in a 61-year-old female patient with a history of total thyroidectomy for thyroiditis and nodules. The patient presented to emergency room with cough and right chest pain and underwent a chest computed tomographic angiogram (CTA) to exclude pulmonary embolism as part of chest pain workup. One right paratracheal mediastinal soft tissue nodule was visualized on the images of CTA. This right paratracheal soft tissue mass was found to be ectopic benign thyroid tissue by histological analysis of the biopsied tissue samples. The function of this ectopic thyroid tissue was characterized by I-123 radioiodine uptake and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. This case illustrates that ectopic thyroid tissue should be included for differential diagnosis of a hyperdense soft tissue mass located within mediastinum. I-123 SPECT/CT is useful for guiding tissue biopsy of ectopic thyroid tissue distant from orthotopic thyroid gland and functional and anatomic characterization of mediastinal ectopic thyroid tissue for surgical resection when it is medically necessary.

Age-dependent changes of cerebral copper metabolism in Atp7b -/- knockout mouse model of Wilson's disease by [64Cu]CuCl2-PET/CT.

Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b -/- knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [64C]CuCl2 in Atp7b -/- knockout mice, PET quantitative analysis revealed low 64Cu radioactivity in the brains of Atp7b -/- knockout mice at 7th weeks of age, compared with 64Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [64C]CuCl2 as a tracer. Furthermore, age-dependent increase of 64Cu radioactivity was detected in the brains of Atp7b -/- knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b -/- knockout mice with orally administered [64Cu]CuCl2 as a tracer. The findings of this study support clinical use of [64Cu]CuCl2-PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

Immune-mediated Disease in Ipilimumab Immunotherapy of Melanoma with FDG PET-CT.

RATIONALE AND OBJECTIVES: The purposes of this study were to provide a case-based overview of various immune-mediated side effects detected by 18F-Fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) in the patients receiving ipilimumab immunotherapy for treatment of malignant melanoma, and discuss the importance of recognizing immune-mediated side effects in the use of F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on metastatic melanoma. MATERIALS AND METHODS: This is a retrospective case series study of the patients diagnosed with melanoma who were subjected to immunomodulating therapy with ipilimumab. F-18 FDG PET-CT findings were reviewed, and the patients with immune-mediated side effects were selected for further analysis, in conjunction with review of clinical progress notes, the results of laboratory tests, and findings of other imaging tests. RESULTS: Four patients with immune-mediated side effects were identified among the patients being treated with ipilimumab and subjected to F-18 FDG PET-CT for monitoring therapeutic effects. These immune mediated side effects include new findings of abnormal increased FDG uptake associated with immune-mediated pancreatitis and hypophysitis, as well as immune-mediated thyroiditis and colitis reported previously. CONCLUSIONS: Various immune-mediated side effects were detected by F-18 FDG PET-CT in the patients subjected to immunomodulating therapy with ipilimumab. It is essential for the interpreting provider to recognize and differentiate abnormal FDG uptake associated with immune-mediated side effects from hypermetabolic malignant lesions when using F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on melanoma lesions.

Asymmetric radiotracer activity of enlarged cerebral spinal fluid space on radionuclide cisternography with SPET/CT.

OBJECTIVE: Cerebrospinal fluid (CSF) leak is a well-known complication of skull or sinus surgery. Radionuclide cisternography has high sensitivity for detection of CSF leak, commonly performed in conjunction with radioactivity assay of nasal pledgets. Our objective was to highlight the usefulness of single photon emission tomography/computed tomography (SPET/CT) in radionuclide cisternography by presenting a case of a 41 years old man with right sided rhinorrhea following craniotomies and sinus surgery, who was subjected to radioactivity assay of nasal pledgets and radionuclide cisternography for suspected CSF leak. Although no CSF leak was detected by radioactivity assay of pledgets placed in the nasal cavity, asymmetric radiotracer activity was noted on cisternographic images in the left temporal region, which was found to correspond to an enlarged CSF space in the left middle cranial fossa, not CSF leak, on SPET/CT images. CONCLUSION: SPET/CT was useful in the differentiation of asymmetric CSF radiotracer activity caused by a normal variant or post surgical changes of anatomic structures from abnormal radiotracer activity secondary to CSF leakage on radionuclide cisternography.

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

Assessment of Traumatic Brain Injury by Increased 64Cu Uptake on 64CuCl2 PET/CT.

UNLABELLED: Copper is a nutritional trace element required for cell proliferation and wound repair. METHODS: To explore increased copper uptake as a biomarker for noninvasive assessment of traumatic brain injury (TBI), experimental TBI in C57BL/6 mice was induced by controlled cortical impact, and (64)Cu uptake in the injured cortex was assessed with (64)CuCl2 PET/CT. RESULTS: At 24 h after intravenous injection of the tracer, uptake was significantly higher in the injured cortex of TBI mice (1.15 ± 0.53 percentage injected dose per gram of tissue [%ID/g]) than in the uninjured cortex of mice without TBI (0.53 ± 0.07 %ID/g, P = 0.027) or the cortex of mice that received an intracortical injection of zymosan A (0.62 ± 0.22 %ID/g, P = 0.025). Furthermore, uptake in the traumatized cortex of untreated TBI mice (1.15 ± 0.53 %ID/g) did not significantly differ from that in minocycline-treated TBI mice (0.93 ± 0.30 %ID/g, P = 0.33). CONCLUSION: Overall, the data suggest that increased (64)Cu uptake in traumatized brain tissues holds potential as a new biomarker for noninvasive assessment of TBI with (64)CuCl2 PET/CT.

Detection of Widespread Metastasis in a Case of Aggressive Carcinoma Showing Thymuslike Differentiation (CASTLE Disease) Using 18F-FDG PET/CT.

A 30-year-old man had a diagnosis of aggressive carcinoma showing thymuslike differentiation (CASTLE disease) and underwent thyroidectomy for tumor resection and bilateral cervical lymph node dissection. Multiple hypermetabolic nodal metastases were detected in the neck and upper mediastinum with fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT). The patient received radiation therapy and chemotherapy for treatment of metastases. Follow-up (18)F-FDG PET/CT demonstrated resolution of several hypermetabolic lesions previously seen in the neck, but innumerable new hypermetabolic metastatic lesions were visualized. The patient died of this aggressive CASTLE disease despite treatment with surgery, radiation, and systemic chemotherapy.