Condensation of SEUSS promotes hyperosmotic stress tolerance in Arabidopsis.

Osmotic stress imposed by drought and high salinity inhibits plant growth and crop yield. However, our current knowledge on the mechanism by which plants sense osmotic stress is still limited. Here, we identify the transcriptional regulator SEUSS (SEU) as a key player in hyperosmotic stress response in Arabidopsis. SEU rapidly coalesces into liquid-like nuclear condensates when extracellular osmolarity increases. The intrinsically disordered region 1 (IDR1) of SEU is responsible for its condensation. IDR1 undergoes conformational changes to adopt more compact states after an increase in molecular crowding both in vitro and in cells, and two predicted α-helical peptides are required. SEU condensation is indispensable for osmotic stress tolerance, and loss of SEU dramatically compromises the expression of stress tolerance genes. Our work uncovers a critical role of biomolecular condensates in cellular stress perception and response and expands our understanding of the osmotic stress pathway.

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.

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.

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.

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.

Synthesis and characterization of Her2-NLP peptide conjugates targeting circulating breast cancer cells: cellular uptake and localization by fluorescent microscopic imaging.

To synthesize a fluorescent Her2-NLP peptide conjugate consisting of Her2/neu targeting peptide and nuclear localization sequence peptide (NLP) and assess its cellular uptake and intracellular localization for radionuclide cancer therapy targeting Her2/neu-positive circulating breast cancer cells (CBCC). Fluorescent Cy5.5 Her2-NLP peptide conjugate was synthesized by coupling a bivalent peptide sequence, which consisted of a Her2-binding peptide (NH2-GSGKCCYSL) and an NLP peptide (CGYGPKKKRKVGG) linked by a polyethylene glycol (PEG) chain with 6 repeating units, with an activated Cy5.5 ester. The conjugate was separated and purified by HPLC and then characterized by Maldi-MS. The intracellular localization of fluorescent Cy5.5 Her2-NLP peptide conjugate was assessed by fluorescent microscopic imaging using a confocal microscope after incubation of Cy5.5-Her2-NLP with Her2/neu positive breast cancer cells and Her2/neu negative control breast cancer cells, respectively. Fluorescent signals were detected in cytoplasm of Her2/neu positive breast cancer cells (SKBR-3 and BT474 cell lines), but not or little in cytoplasm of Her2/neu negative breast cancer cells (MDA-MB-231), after incubation of the breast cancer cells with Cy5.5-Her2-NLP conjugates in vitro. No fluorescent signals were detected within the nuclei of Her2/neu positive SKBR-3 and BT474 breast cancer cells, neither Her2/neu negative MDA-MB-231 cells, incubated with the Cy5.5-Her2-NLP peptide conjugates, suggesting poor nuclear localization of the Cy5.5-Her2-NLP conjugates localized within the cytoplasm after their cellular uptake and internalization by the Her2/neu positive breast cancer cells. Her2-binding peptide (KCCYSL) is a promising agent for radionuclide therapy of Her2/neu positive breast cancer using a ß(-) or α emitting radionuclide, but poor nuclear localization of the Her2-NLP peptide conjugates may limit its use for eradication of Her2/neu-positive CBCC using I-125 or other Auger electron emitting radionuclide.

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.

Synthesis and characterization of theranostic poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymer targeting tumor angiogenesis: tumor localization visualized by positron emission tomography.

Poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers were synthesized and characterized for tumor localization in vivo as a theranostic scaffold for cancer imaging and anticancer drug delivery targeting tumor angiogenesis. Tumor localization of the poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers was visualized in mice bearing human prostate cancer xenografts by positron emission tomography (PET) using a microPET scanner. PET quantitative analysis demonstrated that tumor 64Cu radioactivity (2.75 ± 0.34 %ID/g) in tumor-bearing mice 3 hours following intravenous injection of the poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers was significantly higher than the tumor 64Cu radioactivity (1.29 ± 0.26 %ID/g) in tumor-bearing mice injected with the nontargeted poly(HPMA)-DOTA-64Cu copolymers (p = .004). The poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers hold potential as a theranostic scaffold for cancer imaging and radiochemotherapy of prostate cancer targeting tumor angiogenesis by noninvasive tracking with PET.

2-NBDG fluorescence imaging of hypermetabolic circulating tumor cells in mouse xenograft model of breast cancer.

OBJECTIVES: To determine use of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) as a tracer for detection of hypermetabolic circulating tumor cells (CTC) by fluorescence imaging. PROCEDURES: Human breast cancer cells were implanted in the mammary gland fat pad of athymic mice to establish orthotopic human breast cancer xenografts as a mouse model of circulating breast cancer cells. Near-infrared fluorescence imaging of the tumor-bearing mice injected with 2-DeoxyGlucosone 750 (2-DG 750) was conducted to assess glucose metabolism of xenograft tumors. Following incubation with fluorescent 2-NBDG, circulating breast cancer cells in the blood samples collected from the tumor-bearing mice were collected by magnetic separation, followed by fluorescence imaging for 2-NBDG uptake by circulating breast cancer cells, and correlation of the number of hypermetabolic circulating breast cancer cells with tumor size at the time when the blood samples were collected. RESULTS: Human breast cancer xenograft tumors derived from MDA-MB-231, BT474, or SKBR-3 cells were visualized on near-infrared fluorescence imaging of the tumor-bearing mice injected with 2-DG 750. Hypermetabolic circulating breast cancer cells with increased uptake of fluorescent 2-NBDG were detected in the blood samples from tumor-bearing mice and visualized by fluorescence imaging, but not in the blood samples from normal control mice. The number of hypermetabolic circulating breast cancer cells increased along with growth of xenograft tumors, with the number of hypermetabolic circulating breast cancer cells detected in the mice bearing MDA-MB231 xenografts larger than those in the mice bearing BT474 or SKBR-3 xenograft tumors. CONCLUSIONS: Circulating breast cancer cells with increased uptake of fluorescent 2-NBDG were detected in mice bearing human breast cancer xenograft tumors by fluorescence imaging, suggesting clinical use of 2-NBDG as a tracer for fluorescence imaging of hypermetabolic circulating breast cancer cells.

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.

Clinical Characteristics and Risk of Diabetic Complications in Data-Driven Clusters Among Type 2 Diabetes.

Background: This study aimed to cluster newly diagnosed patients and patients with long-term diabetes and to explore the clinical characteristics, risk of diabetes complications, and medication treatment related to each cluster. Research Design and Methods: K-means clustering analysis was performed on 1,060 Chinese patients with type 2 diabetes based on five variables (HbA1c, age at diagnosis, BMI, HOMA2-IR, and HOMA2-B). The clinical features, risk of diabetic complications, and the utilization of elven types of medications agents related to each cluster were evaluated with the chi-square test and the Tukey-Kramer method. Results: Four replicable clusters were identified, severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). In terms of clinical characteristics, there were significant differences in blood pressure, renal function, and lipids among clusters. Furthermore, individuals in SIRD had the highest prevalence of stages 2 and 3 chronic kidney disease (CKD) (57%) and diabetic peripheral neuropathy (DPN) (67%), while individuals in SIDD had the highest risk of diabetic retinopathy (32%), albuminuria (31%) and lower extremity arterial disease (LEAD) (13%). Additionally, the difference in medication treatment of clusters were observed in metformin (p = 0.012), α-glucosidase inhibitor (AGI) (p = 0.006), dipeptidyl peptidase 4 inhibitor (DPP-4) (p = 0.017), glucagon-like peptide-1 (GLP-1) (p <0.001), insulin (p <0.001), and statins (p = 0.006). Conclusions: The newly diagnosed patients and patients with long-term diabetes can be consistently clustered into featured clusters. Each cluster had significantly different patient characteristics, risk of diabetic complications, and medication treatment.

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.

Decreased striatal vesicular monoamine transporter 2 (VMAT2) expression in a type 1 diabetic rat model: A longitudinal study using micro-PET/CT.

AIMS: Diabetes mellitus is a risk factor for Parkinson's disease. These diseases share similar pathogenic pathways, such as mitochondrial dysfunction, inflammation, and altered metabolism. Despite these similarities, the pathogenic relationship between these two diseases is unclear. [18F]FP-(+)-DTBZ is a promising radiotracer targeting VMAT2, which has been used to measure ß-cell mass and to diagnose Parkinson's disease. The aim of this study was to examine the effect of type 1 diabetes on VMAT2 expression in the striatum using [18F]FP-(+)-DTBZ. MATERIALS AND METHODS: A longitudinal study of type 1 diabetic rats was established by intraperitoneally injecting male Wistar rats with streptozotocin. Rats injected with saline were used as the control group. Glucose level, body weight, and [18F]FP-(+)-DTBZ uptake in the striatum and pancreas were evaluated at 0.5, 1, 4, 6 and 12 months after STZ or saline injection. RESULTS: At one-half month post-STZ injection, the glucose levels in these rats increased and then returned to a normal level at 6 months. Along with increased glucose levels, body weight was also decreased significantly and returned slowly to a normal level. ß-Cell mass and striatal [18F]FP-(+)-DTBZ uptake were impaired significantly at 2 weeks post-STZ injection in type 1 diabetic rats and returned to a normal level at 6 and 4 months post-STZ injection. CONCLUSIONS: Due to increased glucose levels and decreased ß-cell mass, decreased [18F]FP-(+)-DTBZ uptake in the striatum was observed in type 1 diabetic rats. Decreased BCM and increased glucose levels were correlated with VMAT2 expression in the striatum which indicated DM is a risk factor for PD.

Quantification of tryptophan transport and metabolism in lung tumors using PET.

UNLABELLED: Abnormal tryptophan metabolism catalyzed by indoleamine 2,3-dioxygenase may play a prominent role in tumor immunoresistance in many tumor types, including lung tumors. The goal of this study was to evaluate the in vivo kinetics of alpha-(11)C-methyl-l-tryptophan (AMT), a PET tracer for tryptophan metabolism, in human lung tumors. METHODS: Tracer transport and metabolic rates were evaluated in 18 lesions of 10 patients using dynamic PET/CT with AMT. The kinetic values were compared between tumors and unaffected lung tissue, tested against a simplified analytic approach requiring no arterial blood sampling, and correlated with standardized uptake values (SUVs) obtained from (18)F-FDG PET/CT scans. RESULTS: Most non-small cell lung cancers (NSCLCs) showed prolonged retention of AMT, but 3 other lesions (2 benign lesions and a rectal cancer metastasis) and unaffected lung tissue showed no such retention. Transport and metabolic rates of AMT were substantially higher in NSCLCs than in the other tumors and unaffected lung tissue. A simplified analytic approach provided an excellent estimate of transport rates but only suboptimal approximation of tryptophan metabolic rates. (18)F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates. CONCLUSION: Prolonged retention of AMT in NSCLCs suggests high metabolic rates of tryptophan in these tumors. AMT PET/CT may be a clinically useful molecular imaging method for personalized cancer treatment by identifying and monitoring patients who have increased tumor tryptophan metabolism and are potentially sensitive to immunopharmacotherapy with indoleamine 2,3-dioxygenase inhibitors.

Positron emission tomography in subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL), an uncommon disorder, was diagnosed in a 17-year-old female when she presented with multiple hard subcutaneous masses that developed over 3 years. She was treated on chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone. Pre- and post-treatment positron emission tomography study demonstrated dramatic resolution of the subcutaneous lesions indicating its usefulness in SPTCL staging and treatment response monitoring.

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.