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1.
Sci Rep ; 14(1): 17994, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39097625

ABSTRACT

CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects.


Subject(s)
5'-Nucleotidase , Colonic Neoplasms , Cysteine , Positron-Emission Tomography , Zirconium , Animals , 5'-Nucleotidase/metabolism , Zirconium/chemistry , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/metabolism , Colonic Neoplasms/immunology , Colonic Neoplasms/pathology , Mice , Cell Line, Tumor , Positron-Emission Tomography/methods , Cysteine/metabolism , Humans , Radioisotopes , Female , Mice, Inbred BALB C , Tissue Distribution , Mice, Nude , GPI-Linked Proteins/metabolism , GPI-Linked Proteins/immunology , Immunoglobulin G/immunology , Immunoglobulin G/metabolism
2.
Commun Biol ; 7(1): 785, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951178

ABSTRACT

Accurate, rapid and non-invasive cancer cell phenotyping is a pressing concern across the life sciences, as standard immuno-chemical imaging and omics require extended sample manipulation. Here we combine Raman micro-spectroscopy and phase tomography to achieve label-free morpho-molecular profiling of human colon cancer cells, following the adenoma, carcinoma, and metastasis disease progression, in living and unperturbed conditions. We describe how to decode and interpret quantitative chemical and co-registered morphological cell traits from Raman fingerprint spectra and refractive index tomograms. Our multimodal imaging strategy rapidly distinguishes cancer phenotypes, limiting observations to a low number of pristine cells in culture. This synergistic dataset allows us to study independent or correlated information in spectral and tomographic maps, and how it benefits cell type inference. This method is a valuable asset in biomedical research, particularly when biological material is in short supply, and it holds the potential for non-invasive monitoring of cancer progression in living organisms.


Subject(s)
Phenotype , Spectrum Analysis, Raman , Humans , Spectrum Analysis, Raman/methods , Colonic Neoplasms/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/metabolism , Cell Line, Tumor
3.
Sci Rep ; 14(1): 17145, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060367

ABSTRACT

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUCReader1: 0.636, AUCReader2: 0.55 vs MRI AUCReader1: 0.829 AUCReader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters.


Subject(s)
Colonic Neoplasms , Magnetic Resonance Imaging , Neoplasm Staging , Tomography, X-Ray Computed , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Male , Female , Middle Aged , Aged , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Prospective Studies , Adult , Aged, 80 and over
4.
Sci Rep ; 14(1): 15673, 2024 07 08.
Article in English | MEDLINE | ID: mdl-38977870

ABSTRACT

Low skeletal muscle index/density (SMI/SMD) is prevalent in cancer, adversely prognostic and associated with tumour stage and the systemic inflammatory response (SIR). Age and SMI/SMD has not been widely studied. The present study analyses the association between age and SMI/SMD after adjustment for other clinicopathological factors. Patients undergoing resectional surgery for TNM Stage I-III disease within the West of Scotland between 2011 and 2014 were identified. A single CT slice was obtained from each patients staging CT scan. SMI and SMD were stratified normal/abnormal. The SIR was stratified using Systemic Inflammatory Grade (SIG). When stratified by age (< 50/50s/60s/70s/80+), 39%/38%/48%/62%/74% and 27%/48%/64%/82%/92% of patients had a low SMI and SMD respectively (both p < 0.001). Older age (OR 1.47, p < 0.001), female sex (OR 1.32, p = 0.032), lower socioeconomic deprivation (OR 1.15, p = 0.004), higher ASA (OR 1.30, p = 0.019), emergency presentation (OR 1.82, p = 0.003), lower BMI (OR 0.67, p < 0.002) and higher SIG (OR 1.23, p < 0.001) were independently associated with low SMI. Older age (OR 2.28, p < 0.001), female sex (OR 1.38, p = 0.038), higher ASA (OR 1.92, p < 0.001), emergency presentation (OR 1.71, p = 0.023), and higher SIG (OR 1.37, p < 0.001) were independently associated with lower SMD. Tumour factors were not independently associated with either SMI/SMD. Age was a major factor associated with low SMI/SMD in patients with colon cancer. Therefore, in these patients it is likely that this represents largely constitutional body composition as opposed to being a disease mediated effect. Adjustment for age is required when considering the cancer mediated effect on SMI/SMD in patients with colon cancer.


Subject(s)
Body Composition , Colonic Neoplasms , Inflammation , Neoplasm Staging , Tomography, X-Ray Computed , Humans , Male , Female , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnostic imaging , Middle Aged , Aged , Aged, 80 and over , Age Factors , Inflammation/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/diagnostic imaging , Adult
5.
Int J Mol Sci ; 25(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39062992

ABSTRACT

[123I]ß-methyl-p-iodophenyl-pentadecanoic acid ([123I]BMIPP), which is used for nuclear medicine imaging of myocardial fatty acid metabolism, accumulates in cancer cells. However, the mechanism of accumulation remains unknown. Therefore, this study aimed to elucidate the accumulation and accumulation mechanism of [123I]BMIPP in cancer cells. We compared the accumulation of [123I]BMIPP in cancer cells with that of [18F]FDG and found that [123I]BMIPP was a much higher accumulation than [18F]FDG. The accumulation of [123I]BMIPP was evaluated in the presence of sulfosuccinimidyl oleate (SSO), a CD36 inhibitor, and lipofermata, a fatty acid transport protein (FATP) inhibitor, under low-temperature conditions and in the presence of etomoxir, a carnitine palmitoyl transferase I (CPT1) inhibitor. The results showed that [123I]BMIPP accumulation was decreased in the presence of SSO and lipofermata in H441, LS180, and DLD-1 cells, suggesting that FATPs and CD36 are involved in [123I]BMIPP uptake in cancer cells. [123I]BMIPP accumulation in all cancer cell lines was significantly decreased at 4 °C compared to that at 37 °C and increased in the presence of etomoxir in all cancer cell lines, suggesting that the accumulation of [123I]BMIPP in cancer cells is metabolically dependent. In a biological distribution study conducted using tumor-bearing mice transplanted with LS180 cells, [123I]BMIPP highly accumulated in not only LS180 cells but also normal tissues and organs (including blood and muscle). The tumor-to-intestine or large intestine ratios of [123I]BMIPP were similar to those of [18F]FDG, and the tumor-to-large-intestine ratios exceeded 1.0 during 30 min after [123I]BMIPP administration in the in vivo study. [123I]BMIPP is taken up by cancer cells via CD36 and FATP and incorporated into mitochondria via CPT1. Therefore, [123I]BMIPP may be useful for imaging cancers with activated fatty acid metabolism, such as colon cancer. However, the development of novel imaging radiotracers based on the chemical structure analog of [123I]BMIPP is needed.


Subject(s)
Colonic Neoplasms , Iodobenzenes , Animals , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Mice , Cell Line, Tumor , Iodobenzenes/chemistry , CD36 Antigens/metabolism , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/metabolism , Iodine Radioisotopes , Oleic Acids/chemistry , Myocardium/metabolism , Tissue Distribution , Fatty Acid Transport Proteins/metabolism , Fluorodeoxyglucose F18/chemistry , Fluorodeoxyglucose F18/metabolism , Fatty Acids
7.
Comput Biol Med ; 178: 108780, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38909447

ABSTRACT

Colon adenocarcinoma (COAD) is a type of colon cancers with a high mortality rate. Its early symptoms are not obvious, and its late stage is accompanied by various complications that seriously endanger patients' lives. To assist in the early diagnosis of COAD and improve the detection efficiency of COAD, this paper proposes a multi-level threshold image segmentation (MIS) method based on an enhanced particle swarm algorithm for segmenting COAD images. Firstly, this paper proposes a multi-strategy fusion particle swarm optimization algorithm (DRPSO) with a replacement mechanism. The non-linear inertia weight and sine-cosine learning factors in DRPSO help balance the exploration and exploitation phases of the algorithm. The population reorganization strategy incorporating MGO enhances population diversity and effectively prevents the algorithm from stagnating prematurely. The mutation-based final replacement mechanism enhances the algorithm's ability to escape local optima and helps the algorithm to obtain highly accurate solutions. In addition, comparison experiments on the CEC2020 and CEC2022 test sets show that DRPSO outperforms other state-of-the-art algorithms in terms of convergence accuracy and speed. Secondly, by combining the non-local mean 2D histogram and 2D Renyi entropy, this paper proposes a DRPSO algorithm based MIS method, which is successfully applied to the segments the COAD pathology image problem. The results of segmentation experiments show that the above method obtains relatively higher quality segmented images with superior performance metrics: PSNR = 23.556, SSIM = 0.825, and FSIM = 0.922. In conclusion, the MIS method based on the DRPSO algorithm shows great potential in assisting COAD diagnosis and in pathology image segmentation.


Subject(s)
Algorithms , Colonic Neoplasms , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Image Interpretation, Computer-Assisted/methods , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Image Processing, Computer-Assisted/methods
8.
J Cancer Res Clin Oncol ; 150(5): 265, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769201

ABSTRACT

BACKGROUND: Incidental colorectal fluorodeoxyglucose (FDG) uptake, observed during positron emission tomography/computed tomography (PET/CT) scans, attracts particular attention due to its potential to represent both benign and pre-malignant/malignant lesions. Early detection and excision of these lesions are crucial for preventing cancer development and reducing mortality. This research aims to evaluate the correlation between incidental colorectal FDG uptake on PET/CT with colonoscopic and histopathological results. METHODS: Retrospective analysis was performed on data from all patients who underwent PET/CT between December 2019 and December 2023 in our hospital. The study included 79 patients with incidental colonic FDG uptake who underwent endoscopy. Patient characteristics, imaging parameters, and the corresponding colonoscopy and histopathological results were studied. A comparative analysis was performed among the findings from each of these modalities. The optimal cut-off value of SUVmax for 18F-FDG PET/CT diagnosis of premalignant and malignant lesions was determined by receiver operating characteristic (ROC) curves. The area under the curve (AUC) of SUVmax and the combined parameters of SUVmax and colonic wall thickening (CWT) were analyzed. RESULTS: Among the 79 patients with incidental colorectal FDG uptake, histopathology revealed malignancy in 22 (27.9%) patients and premalignant polyps in 22 (27.9%) patients. Compared to patients with benign lesions, patients with premalignant and malignant lesions were more likely to undergo a PET/CT scan for primary evaluation (p = 0.013), and more likely to have focal GIT uptake (p = 0.001) and CWT (p = 0.001). A ROC curve analysis was made and assesed a cut-off value of 7.66 SUVmax (sensitivity: 64.9% and specificity: 82.4%) to distinguish premalignant and malignant lesions from benign lesions. The AUCs of the SUVmax and the combined parameters of SUVmax and CWT were 0.758 and 0.832 respectively. CONCLUSION: For patients undergo PET/CT for primary evaluation, imaging features of colorectal focal FDG uptake and CWT were more closely associated with premalignant and malignant lesions. The SUVmax helps determine benign and premalignant/malignant lesions of the colorectum. Moreover, the combination of SUVmax and CWT parameters have higher accuracy in estimating premalignant and malignant lesions than SUVmax.


Subject(s)
Colonoscopy , Fluorodeoxyglucose F18 , Incidental Findings , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Positron Emission Tomography Computed Tomography/methods , Male , Female , Middle Aged , Retrospective Studies , Aged , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnosis , Adult , Precancerous Conditions/diagnostic imaging , Precancerous Conditions/pathology , Precancerous Conditions/diagnosis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/diagnosis , Aged, 80 and over , Clinical Relevance
9.
BMC Med Imaging ; 24(1): 116, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773384

ABSTRACT

OBJECTIVE: Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. METHODS: Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD < 35/field of view, n = 52 cases) and a high MVD group (MVD ≥ 35/field of view, n = 30 cases) using a median of 35/field of view as the MVD grouping criterion. The collected data were statistically analyzed, the subjects' operating characteristic curve (ROC) was plotted, and the area under curve (AUC), sensitivity, specificity, and Yoden index were calculated for the predicted efficacy of each parameter of the energy spectrum and perfusion CT and the combined parameters. RESULTS: The CT values, IC, NIC, λ, Eff-Z of 40kev∼140kev single energy in the arterial and venous phase of colorectal cancer in the high MVD group were higher than those in the low MVD group, and the differences were all statistically significant (p < 0.05). The AUC of each single-energy CT value in the arterial phase from 40 kev to 120 kev for determining the high or low MVD of colorectal cancer was greater than 0.8, indicating that arterial stage has a good predictive value for high or low MVD in colorectal cancer; AUC for arterial IC, NIC and IC + NIC were all greater than 0.9, indicating that in arterial colorectal cancer, both single and combined parameters of spectral CT are highly effective in predicting the level of MVD. The AUC of 40 kev to 90 kev single-energy CT values in the intravenous phase was greater than 0.9, and its diagnostic efficacy was more representative; The AUC of IC and NIC in venous stage were greater than 0.8, which indicating that the IC and NIC energy spectrum parameters in venous stage colorectal cancer have a very good predictive value for the difference between high and low MVDs, with the greatest diagnostic efficacy in IC.The values of BV and BF in the high MVD group were higher than those in the low MVD group, and the differences were statistically significant (P < 0.05), and the AUC of BF, BV, and BV + BF were 0.991, 0.733, and 0.997, respectively, with the highest diagnostic efficacy for determining the level of MVD in colorectal cancer by BV + BF. CONCLUSION: One-stop CT energy spectrum and perfusion imaging technology can accurately reflect the MVD in living tumor tissues, which in turn reflects the tumor angiogenesis, and to a certain extent helps to determine the malignancy, invasion and metastasis of living colorectal cancer tumor tissues based on CT energy spectrum and perfusion parameters.


Subject(s)
Neovascularization, Pathologic , Humans , Male , Female , Middle Aged , Aged , Neovascularization, Pathologic/diagnostic imaging , Retrospective Studies , Tomography, X-Ray Computed/methods , Adult , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/blood supply , Rectal Neoplasms/pathology , Aged, 80 and over , Microvascular Density , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/blood supply , Colorectal Neoplasms/pathology , Predictive Value of Tests , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/blood supply , Angiogenesis
10.
Br J Radiol ; 97(1159): 1214-1221, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38648743

ABSTRACT

The treatment landscape for patients with colon cancer is continuously evolving. Risk-adapted treatment strategies, including neoadjuvant chemotherapy and immunotherapy, are slowly finding their way into clinical practice and guidelines. Radiologists are pivotal in guiding clinicians toward the most optimal treatment for each colon cancer patient. This review provides an overview of recent and upcoming advances in the diagnostic management of colon cancer and the radiologist's role in the multidisciplinary approach to treating colon cancer.


Subject(s)
Colonic Neoplasms , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/therapy , Neoadjuvant Therapy/methods , Immunotherapy/methods , Risk Assessment
12.
BMJ Case Rep ; 17(4)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38663897

ABSTRACT

A colonic lipoma is an uncommon lesion that is linked with clinical symptoms in only a small portion of patients. Patients with large lipomas are often referred for major surgery, which is associated with significant morbidity and mortality. In this case, we described a female patient with recurrent episodes of gastrointestinal blood loss, abdominal pain and colocolic intussusceptions due to a large, lumen-filling, obstructive lipoma in the splenic flexure. On abdominal CT, a lesion of 3.6 cm was visualised with a fat-like density without solid components. Considering its benign nature, we intended to preserve the colon by deroofing the upper part of the lesion and then performing a colonoscopy-assisted laparoscopic wedge resection. During reassessment, auto-amputation of part of the lesion was observed, most likely as a result of long-lasting mechanical effects, which made it possible to perform solely a wedge resection with an excellent outcome.


Subject(s)
Colonic Neoplasms , Colonoscopy , Laparoscopy , Lipoma , Humans , Lipoma/surgery , Lipoma/diagnostic imaging , Female , Colonic Neoplasms/surgery , Colonic Neoplasms/diagnosis , Colonic Neoplasms/diagnostic imaging , Laparoscopy/methods , Colonoscopy/methods , Middle Aged , Tomography, X-Ray Computed , Abdominal Pain/etiology , Intussusception/surgery , Intussusception/diagnostic imaging , Intussusception/diagnosis , Treatment Outcome
13.
Biomed Pharmacother ; 175: 116669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677243

ABSTRACT

BACKGROUND: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. METHODS: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. RESULTS: The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. CONCLUSIONS: The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice.


Subject(s)
Antibodies, Bispecific , CTLA-4 Antigen , Positron Emission Tomography Computed Tomography , Programmed Cell Death 1 Receptor , Animals , Antibodies, Bispecific/pharmacology , Antibodies, Bispecific/immunology , Humans , Mice , CTLA-4 Antigen/immunology , Cell Line, Tumor , Positron Emission Tomography Computed Tomography/methods , Programmed Cell Death 1 Receptor/immunology , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/immunology , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Iodine Radioisotopes , Xenograft Model Antitumor Assays , Tissue Distribution , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/drug effects , Female
14.
Clin Nucl Med ; 49(6): 543-545, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38598733

ABSTRACT

ABSTRACT: An 85-year-old man with prostate cancer and de novo bone metastases was treated with hormonal therapy with resolution of bone lesions, improved primary disease, and improved serum tumor markers. Although on hormonal therapy, biochemical recurrence prompted performance of 18 F-fluciclovine PET/CT. Fluciclovine PET/CT revealed primary prostate cancer progression with incidental note of avid foci in the colon for which colonoscopy was recommended. Colonoscopy with biopsy was performed with pathology revealing primary colon adenocarcinoma. Before reinitiation of prostate cancer therapy, segmental colon resection was performed with pathology positive for additional sites of colon cancer.


Subject(s)
Adenocarcinoma , Carboxylic Acids , Colonic Neoplasms , Cyclobutanes , Positron Emission Tomography Computed Tomography , Humans , Male , Adenocarcinoma/diagnostic imaging , Colonic Neoplasms/diagnostic imaging , Aged, 80 and over , Tomography, X-Ray Computed , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology
15.
Clin J Gastroenterol ; 17(3): 461-465, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38607542

ABSTRACT

A 61-year-old man present to us with continued abdominal pain without abdominal tenderness for 1 month. Blood testing showed elevated biliary enzymes and inflammation. Contrast-enhanced computed tomography (CT) revealed thickening of the transverse colon with relatively strong enhancement but no bile duct dilatation. Colonoscopy revealed localized edema and granular mucosa in the transverse colon. Fluoroscopic endoscopy exhibited the absence of haustra. Multiple biopsies were performed, but differentiation between mild inflammation and mucosa-associated lymphoid tissue (MALT) lymphoma was inconclusive. To establish a definitive diagnosis, transgastric endoscopic ultrasound-guided fine needle biopsy of the hypoechoic mass was performed. Histopathological analysis exhibited the proliferation of small-sized lymphocytes. Fluorescence in situ hybridization revealed the characteristic API2-MALT1 translocation of MALT lymphoma. We performed liver biopsy to investigate biliary enzyme elevation. Histopathology confirmed lymphocytic infiltration within Glisson's capsule. Immunohistochemistry showed positive for CD20 and negative for CD3 and CD5, signifying the infiltration of MALT lymphoma in the liver. Based on these findings, we diagnosed MALT lymphoma, Lugano classification Stage IV. We performed bendamustine-rituximab (BR)-combined therapy. After six courses of BR-combined therapy, colonoscopy revealed improvement in the lead pipe sign and CT revealed disappearance of the mass.


Subject(s)
Colon, Transverse , Colonic Neoplasms , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Lymphoma, B-Cell, Marginal Zone , Humans , Male , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/diagnosis , Middle Aged , Colon, Transverse/pathology , Colon, Transverse/diagnostic imaging , Colonic Neoplasms/pathology , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/diagnosis , Rituximab/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonoscopy , Bendamustine Hydrochloride/administration & dosage , Tomography, X-Ray Computed
18.
Free Radic Biol Med ; 218: 57-67, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38574976

ABSTRACT

Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.


Subject(s)
Feasibility Studies , Fluorodeoxyglucose F18 , Glucose , Multimodal Imaging , Oxidation-Reduction , Animals , Humans , Mice , Fluorodeoxyglucose F18/metabolism , Glucose/metabolism , Multimodal Imaging/methods , Electron Spin Resonance Spectroscopy/methods , Buthionine Sulfoximine/pharmacology , Autoradiography , HCT116 Cells , Colonic Neoplasms/metabolism , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Radiopharmaceuticals/metabolism , Positron-Emission Tomography/methods , Xenograft Model Antitumor Assays , Glutathione/metabolism , Mice, Nude
19.
Nihon Shokakibyo Gakkai Zasshi ; 121(4): 315-320, 2024.
Article in Japanese | MEDLINE | ID: mdl-38599842

ABSTRACT

An 89-year-old man was diagnosed with a submucosal tumor suspected to be a lipoma and was followed up for 6 years. The patient was admitted to the hospital because of increased tumor size and morphological changes despite negative bioptic findings. The lesion was diagnosed as an advanced adenocarcinoma of the ascending colon (cT3N0M0, cStage IIa). Laparoscopic-assisted right hemicolectomy with D3 lymph node dissection was performed. Pathological diagnosis of a surgically resected specimen revealed adenocarcinoma with lipohyperplasia (pT3N2aM0, pStage IIIb). Reports of colon cancer accompanied by colonic lipomas or lipohyperplasia are limited. This case showed an interesting submucosal tumor-like morphology because the cancer developed at the base of the lipohyperplasia and grew and spread below it.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Male , Humans , Aged, 80 and over , Colon, Ascending/pathology , Colon, Ascending/surgery , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/etiology , Colonic Neoplasms/surgery , Ileum , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/etiology , Adenocarcinoma/surgery , Hyperplasia/complications , Hyperplasia/pathology
20.
Abdom Radiol (NY) ; 49(6): 1792-1804, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38446179

ABSTRACT

PURPOSE: To investigate the performance of computed tomography (CT) in the local staging of colon cancer in different segments, with emphasis on parameters that have been found to be significant for rectal cancer, namely, extramural venous invasion (EMVI) and tumor deposits (TDs). METHODS: CT and pathology data from 137 patients were independently reviewed by radiology and pathology teams. The performance of CT in categorizing a given patient into good, versus poor prognostic groups was assessed for each segment, as well as the presence of lymph nodes (LNs), TDs and EMVIs. Discordant cases were re-evaluated to determine potential sources of error. Elastic stain was applied for EMVI discordance. RESULTS: The T staging accuracy was 80.2%. For T stage stratification, CT performed slightly better in the left colon, and the lowest accuracy was in the transverse colon. Under-staging was more common (in 12.4%), and most of the mis-staged cases were in sigmoid colon. According to the first comprehensive correlative analysis, the sensitivity, specificity, and accuracy of CT for detecting TDs were found to be 57.9%, 92.4%, 87.6%, respectively. These figures were 44.7%, 72.7%, and 63.5% for LN, and 58.5%, 82.1% and 73% for EMVI. The detection rate was better for multifocal EMVI. The detection rate was also comparable (although substantially underestimated) for LNs, with the half of the LNs missed by CT being < 5 mm. Four patients that were classified as TD by CT, disclosed to be LNs by pathology. Correlative analysis led to refinement of the pathology criteria, with subsequent modifications of the initial reports in 13 (9.5%) patients. CONCLUSION: Overall, CT performed well in the evaluation of colon cancer, as did TD and EMVI. It is advisable to include these parameters in CT-based staging. Radiologists should be aware of the pitfalls that occur more commonly in different segments.


Subject(s)
Colonic Neoplasms , Neoplasm Invasiveness , Neoplasm Staging , Sensitivity and Specificity , Tomography, X-Ray Computed , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Male , Female , Aged , Middle Aged , Tomography, X-Ray Computed/methods , Aged, 80 and over , Adult , Retrospective Studies , Contrast Media , Prognosis , Lymphatic Metastasis/diagnostic imaging
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