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We report the case of corneal transplant rejection in a 77-year-old male receiving durvalumab as consolidative therapy for stage IIIB non-small cell lung cancer (NSCLC). Following successful chemoradiation and initiation of durvalumab, the patient underwent a right corneal transplant for corneal dystrophy. Six months after an initially stable post-transplant course, he developed progressive visual decline culminating in graft failure 1 year later despite treatment with prednisone eye drops. This case adds to the limited evidence implicating immune checkpoint inhibitors (ICIs) in corneal graft rejection, emphasizing the need for multidisciplinary evaluation and close monitoring of corneal transplant recipients undergoing ICI therapy.
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Ewing's sarcoma is a kind of undifferentiated reticulocytic sarcoma, which was first reported in 1921 by James Ewing. It is difficult to differentiate Ewing's sarcoma from osteomyelitis on computed tomography (CT) and X-ray and hence cytological confirmation is needed. Fluorodeoxy glucose being a nonspecific tracer cannot differentiate between malignant and inflammatory lesions. However, it is found that Ewing's sarcoma has increased LAT1 transporter expression at the cell surface. This property has been utilized to specifically target the tumor cells and differentiate them from inflammatory lesions. 18F-fluoroethyl tyrosine (FET) is a radiotracer which shows increased uptake in tumors having LAT1 expression and no uptake in inflammatory lesions. Thus, FET positron emission tomography-computed tomography can serve as a useful tool in diagnosing recurrence or residual Ewing's sarcoma from infective pathology. Besides, it is also helpful in monitoring response to therapy.
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Sustaining attention to the task at hand is a crucial part of everyday life, from following a lecture at school to maintaining focus while driving. Lapses in sustained attention are frequent and often problematic, with conditions such as attention deficit hyperactivity disorder affecting millions of people worldwide. Recent work has had some success in finding signatures of sustained attention in whole-brain functional connectivity (FC) measures during basic tasks, but since FC can be dynamic and task-dependent, it remains unclear how fully these signatures would generalize to a more complex and naturalistic scenario. To this end, we used a previously defined whole-brain FC network - a marker of attention that was derived from a sustained attention task - to predict the ability of participants to recall material during a free-viewing reading task. Though the predictive network was trained on a different task and set of participants, the strength of FC in the sustained attention network predicted reading recall significantly better than permutation tests where behavior was scrambled to simulate chance performance. To test the generalization of the method used to derive the sustained attention network, we applied the same method to our reading task data to find a new FC network whose strength specifically predicts reading recall. Even though the sustained attention network provided significant prediction of recall, the reading network was more predictive of recall accuracy. The new reading network's spatial distribution indicates that reading recall is highest when temporal pole regions have higher FC with left occipital regions and lower FC with bilateral supramarginal gyrus. Right cerebellar to right frontal connectivity is also indicative of poor reading recall. We examine these and other differences between the two predictive FC networks, providing new insight into the task-dependent nature of FC-based performance metrics.
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Atenção/fisiologia , Encéfalo/fisiologia , Compreensão/fisiologia , Conectoma/métodos , Rememoração Mental/fisiologia , Rede Nervosa/fisiologia , Leitura , Adulto , Biomarcadores , Encéfalo/diagnóstico por imagem , Medições dos Movimentos Oculares , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVES: The purpose of this study was to evaluate the performance of l-[methyl-()11C]methionine (11C-MET) PET/CT and MRI (with the inclusion of advanced imaging techniques, namely, MR spectroscopy and MR perfusion) in the assessment of tumor recurrence in high-grade gliomas. PATIENTS AND METHODS: Twenty-nine patients with high-grade gliomas who underwent surgical resection, external beam radiation therapy, and standard regimens of chemotherapy were subjected to MRI (conventional, MR perfusion, and MR spectroscopy) and 11C-MET PET/CT scans. A definitive diagnosis was made based on histopathology and/or long-term clinical and radiological follow-up. Several indices were obtained for lesion characterization, namely, SUVmean, SUVmax, and mean lesion-to-normal tissue on PET/CT, as well as relative cerebral blood volume and choline-to-creatine ratio on MRI. RESULTS: Histological examination revealed viable tumor cells in 19 cases, whereas the remaining 10 were deemed to be negative based on histology (3 cases) or long-term follow-up (7 cases). All the quantitative indices mentioned previously tended to be higher in patients with tumor recurrence/residual. The sensitivity, specificity, and accuracy of 11C-MET PET/CT in identifying tumor recurrence/residual were 94.7%, 80%, and 89.6%, respectively, whereas that of MRI were 84.2%, 90%, and 86.2%, respectively. CONCLUSIONS: Both 11C-MET PET/CT and MRI (with the inclusion of advanced MRI techniques) demonstrated a high diagnostic performance in the identification of tumor residual/recurrence in high-grade gliomas posttherapy. Although 11C-MET PET/CT seemed to be more sensitive, whereas advanced MRI seemed more specific, there was no statistically significant difference in the diagnostic performance of either modality in the present study. Further studies with a larger group of patients are warranted.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem Multimodal , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Radioisótopos de Carbono , Feminino , Glioma/patologia , Glioma/terapia , Humanos , Masculino , Metionina/análogos & derivados , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos RadiofarmacêuticosRESUMO
Epidermal growth factor receptor (EGFR) signaling inhibition represents a highly promising arena for the application of molecularly targeted cancer therapies. EGFR conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress EGFR receptors. Through improved understanding of EGFR biology in human cancers, there is anticipation that more tumor-selective therapy approaches with diminished collateral normal tissue toxicity can be advanced. We report here on the results with a thermodynamically stable chelate, 1,4,7-tris(carboxymethyl)-10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane (DO3A-EA) and anti-EGFr (ior egf/r3) conjugate to develop immunospecific imaging agent. Conjugation and labelling with anti-EGFr was performed using standard procedure and subjected to purification on size exclusion chromatography. The conjugated antibodies were labeled with a specific activity 20-30 mCi/mg of protein. Labeling efficiencies were measured by ascending paper chromatography on ITLC-SG strips. Radiolabeling of the immunoconjugate was found to be 98.5 ± 0.30%. (99m)Tc-DO3A-EA-EGFr conjugate was studied in athymic mice bearing U-87MG, MDA-MB-468 tumors following intravenous injection. Pharmacokinetic and biodistribution studies confirmed long circulation times (t(1/2)(fast)â =â 45 min and t1/2(slow)â = 4 hours 40 min) and efficient accumulation in tumors. Biodistribution studies in athymic mice grafted with U-87MG human glioblastoma multiforme and Hela human cervical carcinoma tumors revealed significant localization of (99m)Tc-labeled antibodies conjugate in tumors and reduced accumulation in normal organs. This new chelating agent is promising for immunoscintigraphy since good tumour-to-normal organ contrast could be demonstrated. These properties can be exploited for immunospecifc contrast agents in nuclear medicine and SPECT imaging.
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Anticorpos Monoclonais/farmacocinética , Receptores ErbB/antagonistas & inibidores , Glioma/tratamento farmacológico , Compostos Heterocíclicos com 1 Anel/farmacocinética , Imunotoxinas/farmacocinética , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Quelantes/química , Meios de Contraste/química , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Receptores ErbB/imunologia , Glioma/imunologia , Glioma/metabolismo , Células HeLa , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Compostos Heterocíclicos com 1 Anel/química , Humanos , Imunotoxinas/administração & dosagem , Imunotoxinas/química , Imunotoxinas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular/métodos , Terapia de Alvo Molecular , Coelhos , Cintilografia , Tecnécio , Imagem Corporal Total , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) has limited specificity in the evaluation of intracranial lesions as it is taken up by inflammatory and granulomatous lesions as well. 11C-methionine is known to have a higher specificity in tumor detection, delineation, and differentiation of benign from malignant lesions. However, its uptake in granulomatous lesions remains unclarified. OBJECTIVE: The aim of this study was to explore the value of 11C-methionine PET/CT and 18F-FDG in the evaluation of intracranial tuberculomas. METHODS: 11C-methionine PET/CT followed by 18F-FDG PET/CT study was performed on 12 patients with intracranial tuberculomas. The diagnosis was confirmed for all cases on histopathological evaluation and/or follow-up. Quantitative analysis was performed for all cases by measuring the lesion-to-normal gray matter uptake ratio. RESULTS: A high lesion-to-normal gray matter uptake ratio was observed on both 11C-methionine (1.8 ± 0.38) and 18F-FDG scans (1.64 ± 0.26) in all newly diagnosed cases. Lesion detection and delineation was superior on 11C-methionine PET/CT. In addition, 11C-methionine appeared to be a more sensitive indicator for assessing early therapeutic response and incomplete therapeutic response in intracranial tuberculomas. There was complete concordance in the number and sites of lesions detected on 11C-methionine PET/CT and radiological imaging modalities (namely, CT and MRI). CONCLUSION: This preliminary study suggests that in newly diagnosed, untreated intracranial tuberculomas, 11C-methionine, like 18F-FDG, may have limited specificity in distinguishing it from a neoplastic lesion. However, it may play an important role in assessing the response to antitubercular treatment. Further studies are warranted to explore the potential of 11C-methionine in this regard.
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Encefalopatias/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Metionina/farmacocinética , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Tomografia Computadorizada por Raios X , Tuberculoma Intracraniano/diagnóstico por imagem , Adolescente , Adulto , Radioisótopos de Carbono/farmacocinética , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Although [18F] 2-fluoro-2-deoxy-D-glucose (FDG) is the most widely used radiopharmaceutical the world over, it is not the ideal tracer for brain imaging, owing to its high physiological cortical uptake and lack of specificity. This has paved the way for the introduction of several novel radiotracers, each with their own inherent strengths and limitations. We present the insights gained from the use of these radiotracers at our institution.
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OBJECTIVE: The diagnostic utility of a C-methionine scan has been established in breast cancer. We were able to radiolabel methionine with Tc at our institute. Thus, we undertook clinical trials to determine the role of Tc-methionine scans in the detection of breast cancer. METHODS: Scintimammography was performed in 47 female (median age 44 years, range 28-68 years) patients having palpable breast masses. All of them underwent ultrasound, mammography, fine-needle aspiration cytology, and Tc-methionine scintimammography before surgery. The final diagnosis was made after histopathological examination. Tc-methionine scintimammography was done after injecting 555 MBq of radiotracer intravenously. The results of scintimammography were compared with histopathology. RESULTS: The histopathological findings were malignant in 33 (70%) and benign in 14 (30%) cases. Scintimammography showed true-positive findings in 29 patients out of 33 cases of breast cancer. True-negative findings were found in 13 out of 14 patients having benign breast lesions. The sensitivity, specificity, and positive predictive value were found to be 87.8, 92.8, and 96.6% respectively. CONCLUSION: Tc-methionine imaging can provide useful information with reasonably high sensitivity and specificity in evaluating patients having breast masses.
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Neoplasias da Mama/diagnóstico por imagem , Metionina , Compostos Radiofarmacêuticos , Adulto , Idoso , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/patologia , Radioisótopos de Carbono , Feminino , Humanos , Metástase Linfática , Metionina/farmacocinética , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Sensibilidade e Especificidade , Tecnécio , Distribuição Tecidual , Imagem Corporal TotalRESUMO
The convenient synthetic methodology and in vivo stability of the bone-seeking gamma-radiation-emitting compound, (99m)Tc-DOTMP are described in this paper. The radiolabeling efficiency was found to be >97%, and the stability in serum indicated that (99m)Tc remained bound to the chelate, DOTMP, for up to 24 hours. Blood clearance showed a quick washout from the circulation, and biologic half-life was found to be t(1/2)(F) = 25 min; t(1/2)(S) = 6 hours 5 minutes. The LD(50) was found to be 70 mg/kg, as determined by toxicity studies in BALB/c mice. Biodistribution characteristics of (99m)Tc-DOTMP were examined in BALB/c mice. The drug was excreted mainly through renal routes and the accumulation of (99m)Tc-DOTMP in bone was 9.06 +/- 0.75 percent injected dose per gram at 1 hour. Visual image analysis of (99m)Tc-DOTMP was clinically comparable to the interpretation of imaging studies with conventional (99m)Tc-MDP and other phosphonate derivatives. (99m)Tc-DOTMP injected into Balb/c mice showed prominent bone localization and rapid clearance from blood and other organs, thereby making it a promising candidate as a diagnostic pharmaceutical of bone metastases.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico , Compostos Organofosforados/síntese química , Compostos Organofosforados/farmacologia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Tecnécio/química , Tecnécio/farmacologia , Animais , Quelantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Coelhos , Cintilografia/métodos , Ratos , Fatores de Tempo , Distribuição TecidualRESUMO
INTRODUCTION: We undertook this prospective study to compare amino acid metabolism, glucose metabolism, and proliferation in primary and recurrent low grade gliomas using positron emission tomography (PET)/computed tomography with F-18 FDOPA, F-18 FDG, and F-18 FLT. METHODS: Fifteen patients with newly diagnosed or previously treated low grade gliomas (WHO grade I or II) were subjected to F-18-FDOPA, F-18 FDG, and F-18 FLT PET/computed tomography studies on consecutive days. This included 2 patients in remission as control subjects. Uptake of all the 3 tracers were analyzed visually and quantified using standardized uptake values and tumor to normal (T/N) ratios. The accuracy of all the 3 PET tracers in the detection of newly diagnosed and recurrent low grade gliomas was compared. RESULTS: F-18 FDOPA was positive in all cases of primary and recurrent low grade gliomas and negative in the patients in remission. Tumor was visualized on F-18 FDG in 7 of 13 cases, F-18-FLT was positive in 4 of 13 cases. Average tumor standardized uptake values max for F-18 FDOPA (5.75 +/- 4.9) and F-18 FLT (1.8 +/- 0.91) was lower than that of F-18 FDG (8.5 +/- 4.4). T/N ratios for F-18-FDOPA (2.3 +/- 0.51) and F-18 FLT (1.8 +/- 0.91) were higher than F-18 FDG (1.03 +/- 0.64) providing good image contrast for tumor detection in positive cases. CONCLUSION: F-18 FDOPA scan is superior to both F-18 FLT and F-18 FDG for visualization of primary and recurrent low grade gliomas. F-18-FLT should not be considered for evaluation of recurrent low grade gliomas.
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Neoplasias Encefálicas/diagnóstico , Didesoxinucleosídeos , Di-Hidroxifenilalanina/análogos & derivados , Fluordesoxiglucose F18 , Glioma/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de Subtração , Adulto JovemRESUMO
The tetraphosphonate ligand, 5-amino-1,3-bis(ethylamine-(N,N-dimethyl diphosphonic acid) acetamido) benzene (IPTMP) used in the present study was prepared from 5-nitroisophthalate dimethylester to label with radionuclide for targeted diagnosis and therapy. The synthesized multidentate phosphonate ligand was characterized on the basis of spectroscopic techniques, which exhibited good metal ion control properties when complexed to (99m)Tc with high in vitro and in vivo stability. Excellent quality bone images of rabbit were imaged showing rapid clearance of background activity and visualization of skeleton at 1h.
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Compostos de Organotecnécio/síntese química , Compostos Radiofarmacêuticos/síntese química , Animais , Osso e Ossos/diagnóstico por imagem , Quelantes/síntese química , Cromatografia em Camada Fina , Indicadores e Reagentes , Dose Letal Mediana , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Compostos de Organotecnécio/toxicidade , Ácido Pentético/farmacologia , Tomografia por Emissão de Pósitrons , Controle de Qualidade , Coelhos , Compostos Radiofarmacêuticos/toxicidade , Espectrofotometria Infravermelho , Medronato de Tecnécio Tc 99m , Distribuição TecidualRESUMO
BACKGROUND AND AIM: The development of bone-seeking radiopharmaceuticals for the detection of malignant bone lesions could further improve the diagnostic accuracy of routine bone scanning. This study aimed to provide a convenient synthesis of trans-1,2-cyclohexylenedinitrilo tetramethylene phosphonic acid (CDTMP) and an improved preparation of its (99m)Tc complex. METHODS: CDTMP was prepared from trans-1,2-cyclohexyldinitrilotetraacetic acid by reaction with phosphorus trichloride and it was labelled with (99m)Tc. Toxicity and biodistribution studies were carried out in BALB/c mice, while blood clearance and bone scintigraphy studies were carried out in rabbits. (99m)Tc-CDTMP was evaluated for the detection of malignant bone lesions in 11 patients. Bone scintigraphy (a methylene diphosphonate scan) was performed to detect metastases at diagnosis and follow-up. RESULTS: The radiolabelling efficiency was found to be >97% and the stability in serum indicated that (99m)Tc remained bound to the chelate, CDTMP, for up to 24 h. Blood clearance showed a quick wash-out from the circulation and the biological half-lives (t12) were 55 min (F) and 8 h 48 min (S). The LD50 was 110 mg.kg(-1) as determined by toxicity studies. The drug was excreted mainly through renal route and the accumulation of (99m)Tc-CDTMP in bone was 7.69+/-0.65%ID/g at 1 h. The mean ratio of bone lesion to soft tissue was 6.8+/-0.69 and of bone lesion to normal bone was 5.67+/-0.82. Visual image analysis of (99m)Tc-CDTMP was clinically comparable to the interpretation of imaging studies with (99m)Tc-MDP. CONCLUSION: These preliminary data support increased bone uptake by the tetraphosphonate complex of (99m)Tc. This suggests that CDTMP complexed with therapeutic radionuclides should be evaluated for therapy of skeletal metastases.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Organofosfonatos/farmacocinética , Tecnécio/farmacocinética , Animais , Neoplasias Ósseas/metabolismo , Humanos , Marcação por Isótopo/métodos , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos , Organofosfonatos/química , Coelhos , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tecnécio/química , Distribuição TecidualRESUMO
OBJECTIVE: The purpose of this study was to obtain the convenient, synthetically useful bifunctional chelating agent, 6-(4-isothiocyanatobenzyl)-5,7-dioxo-1,11-(carboxymethyl)-1,4,8,11-tetraazacyclotridecane, and to apply it to stable (99m)Tc-labelling of monoclonal antibodies (mAbs). METHODS: The chelate was synthesised by reaction of nitrobenzyl malonate and triethylenetetramine followed by alkylation by reacting with bromoacetic acid at pH 10. The amino group was converted to isothiocyanato derivative by reacting with thiophosgene at pH 2.0. Conjugation with mAbs [(anti-carcinoembryonic antigen (CEA) and anti-epidermal growth factor receptor (EGFr)] was performed at pH 8.4 using trisodium phosphate solution by incubating at 37 degrees C for 1 h and subjected to purification on size exclusion chromatography. RESULTS: When radioimmunoconjugates were labelled with (99m)Tc, the specific activity of immunoconjugates was 20-30 mCi/mg of protein and their immunoreactivity exceeded 80%. The stability in serum indicated that the metal remained bound to antibodies. Biodistribution studies in athymic mice grafted with U-87 human glioblastoma multiforme and MDA-MB-468 human breast carcinoma tumours revealed significant localisation of (99m)Tc-labelled antibodies in tumours and reduced accumulation in normal organs. CONCLUSION: This bifunctional chelating agent is promising for immunoscintigraphy because of good tumour-to-normal organ contrast.
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Alcanos/análise , Anticorpos Monoclonais/metabolismo , Quelantes/metabolismo , Cintilografia/métodos , Tecnécio/metabolismo , Alcanos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ratos , Ratos Sprague-Dawley , Coloração e Rotulagem/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
A new radiopharmaceutical, 99mTc-Tetraethylenepentamine(TEPA)-Folate has been synthesized introducing TEPA to the gamma-carboxyl group of folic acid. This binds with 99mTc high efficiency at ambient temperature. The resulting 99mTc-N5-Folate is stable under physiological conditions at least for 24 h after radiocomplexation. TEPA is a known open chain pentamine (N5) chelator, its four-nitrogen act as the binding site for 99mTc. The folate membrane receptor binding of the 99mTc-TEPA-Folate by established human tumor cell lines (KB, U-87MG and MDA-MB-468) showed Kd in microM range in normal DMEM (10% serum, 10 microM folic acid). The blood kinetic studies showed more than 70% clearance within five minutes from the circulation. The KB cell line tumors in mice were readily identifiable in the gamma images and revealed major accumulation of radiotracer in liver, kidneys and intestines. High tumor uptake was shown in the tumor bearing nude mice; tumorto-blood ratios reached 2.68 +/- 0.52 and 5.5 +/- 1.47 at 1 and 4 h after post injection respectively. Surviving fractions as obtained in clonogenic assay were 1.02 +/- 0.07 and 1.03 +/- 0.05 in U-87MG and MDA-MB-468 cell lines respectively. The 99mTc-N5-Folate conjugate have promising utility as a receptor specific radiopharmaceutical for imaging neoplastic tissues known to over express folate-binding protein.