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PURPOSE: Glioblastoma multiforme (GBM) is the most common glioma and standard therapies can only slightly prolong the survival. Neo-vascularization is a potential target to image tumor microenvironment, as it defines its brain invasion. We investigate [18F]rhPSMA-7.3 with PET/MRI for quantitative imaging of neo-vascularization in GBM bearing mice and human tumor tissue and compare it to [18F]FET and [18F]fluciclovine using PET pharmacokinetic modeling (PKM). METHODS: [18F]rhPSMA-7.3, [18F]FET, and [18F]fluciclovine were i.v. injected with 10.5 ± 3.1 MBq, 8.0 ± 2.2 MBq, 11.5 ± 1.9 MBq (n = 28, GL261-luc2) and up to 90 min PET/MR imaged 21/28 days after surgery. Regions of interest were delineated on T2-weighted MRI for (i) tumor, (ii) brain, and (iii) the inferior vena cava. Time-activity curves were expressed as SUV mean, SUVR and PKM performed using 1-/2-tissue-compartment models (1TCM, 2TCM), Patlak and Logan analysis (LA). Immunofluorescent staining (IFS), western blotting, and autoradiography of tumor tissue were performed for result validation. RESULTS: [18F]rhPSMA-7.3 showed a tumor uptake with a tumor-to-background-ratio (TBR) = 2.1-2.5, in 15-60 min. PKM (2TCM) confirmed higher K1 (0.34/0.08, p = 0.0012) and volume of distribution VT (0.24/0.1, p = 0.0017) in the tumor region compared to the brain. Linearity in LA and similar k3 = 0.6 and k4 = 0.47 (2TCM, tumor, p = ns) indicated reversible binding. K1, an indicator for vascularization, increased (0.1/0.34, 21 to 28 days, p < 0.005). IFS confirmed co-expression of PSMA and tumor vascularization. [18F]fluciclovine showed higher TBR (2.5/1.8, p < 0.001, 60 min) and VS (1.3/0.7, p < 0.05, tumor) compared to [18F]FET and LA indicated reversible binding. VT increased (p < 0.001, tumor, 21 to 28 days) for [18F]FET (0.5-1.4) and [18F]fluciclovine (0.84-1.5). CONCLUSION: [18F]rhPSMA-7.3 showed to be a potential candidate to investigate the tumor microenvironment of GBM. Following PKM, this uptake was associated with tumor vascularization. In contrast to what is known from PSMA-PET in prostate cancer, reversible binding was found for [18F]rhPSMA-7.3 in GBM, contradicting cellular trapping. Finally, [18F]fluciclovine was superior to [18F]FET rendering it more suitable for PET imaging of GBM.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias de la Próstata , Masculino , Humanos , Animales , Ratones , Glioblastoma/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Tirosina/farmacocinética , Microambiente TumoralRESUMEN
The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.
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Ciclobutanos , Neoplasias de la Próstata , Humanos , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
BACKGROUND: National Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (<2·0 ng/mL). METHODS: This was a prospective, single-centre, open-label, single-arm comparative study done at University of California Los Angeles (Los Angeles, CA, USA). Patients older than 18 years of age with prostate cancer biochemical recurrence after radical prostatectomy and PSA levels ranging from 0·2 to 2·0 ng/mL without any prior salvage therapy and with a Karnofsky performance status of at least 50 were eligible. Patients underwent 18F-fluciclovine (reference test) and PSMA (index test) PET-CT scans within 15 days. Detection rate of biochemical recurrence at the patient level and by anatomical region was the primary endpoint. A statistical power analysis demonstrated that a sample size of 50 patients was needed to show a 22% difference in detection rates in favour of PSMA (test for superiority). Each PET scan was interpreted by three independent masked readers and a consensus majority interpretation was generated (two vs one) to determine positive findings. This study is registered with ClinicalTrials.gov, number NCT02940262, and is complete. FINDINGS: Between Feb 26, 2018, and Sept 20, 2018, 143 patients were screened for eligibility, of whom 50 patients were enrolled into the study. Median follow-up was 8 months (IQR 7-9). The primary endpoint was met; detection rates were significantly lower with 18F-fluciclovine PET-CT (13 [26%; 95% CI 15-40] of 50) than with PSMA PET-CT (28 [56%; 41-70] of 50), with an odds ratio (OR) of 4·8 (95% CI 1·6-19·2; p=0·0026) at the patient level; in the subanalysis of the pelvic nodes region (four [8%; 2-19] with 18F-fluciclovine vs 15 [30%; 18-45] with PSMA PET-CT; OR 12·0 [1·8-513·0], p=0·0034); and in the subanalysis of any extrapelvic lesions (none [0%; 0-6] vs eight [16%; 7-29]; OR non-estimable [95% CI non-estimable], p=0·0078). INTERPRETATION: With higher detection rates, PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations (≤2·0 ng/mL). Further research is needed to investigate whether higher detection rates translate into improved oncological outcomes. FUNDING: None.
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Ácidos Carboxílicos/administración & dosificación , Ciclobutanos/administración & dosificación , Ácido Edético/análogos & derivados , Recurrencia Local de Neoplasia/diagnóstico por imagen , Oligopéptidos/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Medios de Contraste/administración & dosificación , Ácido Edético/administración & dosificación , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Prostatectomía/métodos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugíaRESUMEN
The gold standard to diagnose suspected cardiac amyloidosis is myocardial biopsy. In recent years, bone scintigraphy has partly replaced myocardial biopsy.
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Biopsia , Humanos , CintigrafíaRESUMEN
PURPOSE: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (18F) after biochemical recurrence. MATERIALS AND METHODS: A total of 596 patients underwent fluciclovine (18F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans. RESULTS: The subject level fluciclovine (18F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (18F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (18F) was well tolerated and the safety profile was not altered following repeat administration. CONCLUSIONS: Fluciclovine (18F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.
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Ácidos Carboxílicos , Ciclobutanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: Meticulous imaging of colorectal liver metastases (CRLM) is mandatory to optimize outcome after liver resection. However, the detection of CRLM is still challenging. PURPOSE: To evaluate prospectively if magnetic resonance imaging (MRI) with diffusion-weighted and Gd-EOB-DTPA-enhanced sequences had a better diagnostic performance for CRLM compared to computed tomography (CT) and fluorine-18 fluorodeoxyglucose positron emission tomography (PET/CT). MATERIAL AND METHODS: Forty-six patients scheduled for resection of suspected CRLM were evaluated prospectively from September 2011 to January 2013. None of the patients had undergone previous treatment for their CRLM. Multiphase CT, liver MRI with diffusion-weighted and dynamic Gd-EOB-DTPA-enhanced sequences and low-dose PET/CT were performed. Two independent, blinded readers evaluated the examinations. The reference standard was histopathological confirmation (81/140 CRLM) or follow-up. RESULTS: A total of 140 CRLM and 196 benign lesions were identified. On a per-lesion basis, MRI had the significantly highest sensitivity overall and for CRLM < 10 mm (P < 0.001). Overall sensitivity/specificity and PPV/NPV were 68%/94% and 89%/81% for CT, 90%/87% and 82%/93% for MRI, and 61%/99% and 97%/78% for PET/CT. For CRLM < 10 mm it was 16%/96% and 54%/80% for CT, 74%/88% and 64%/93% for MRI, and 9%/98% and 57%/79% for PET/CT. CONCLUSION: MRI had the significantly highest sensitivity compared with CT and PET/CT, particularly for CRLM < 10 mm. Therefore, detection of CRLM should be based on MRI.
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Neoplasias Colorrectales/patología , Imagen de Difusión por Resonancia Magnética , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Fluorodesoxiglucosa F18 , Gadolinio DTPA , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
Background: 18F-fluciclovine is a positron emission tomography (PET) radiotracer approved for the detection of prostate cancer recurrence. No effect of androgen deprivation therapy (ADT) on its performance has been established. Purpose: To study the impact of concurrent ADT on disease detection with 18F-fluciclovine PET in patients with prostate cancer. Materials and Methods: Data from patients with prostate cancer who had been receiving ADT for ≥3 months at the time of undergoing an 18F-fluciclovine PET/CT at our institution were retrospectively reviewed. Seventy-three scans from 71 patients were included. The scans indicated rising prostate-specific antigen (n = 58), staging advanced disease (n = 4) or therapeutic monitoring (n = 9). Patients' medical records provided baseline clinical data and post-scan outcomes (median follow-up 40 months). Results: Malignant lesions with increased uptake of 18F-fluciclovine were detected in 60/73 (82%) scans; 33 (45%) had lesions in the prostate/bed and 46 (63%) in extraprostatic sites. Patients received ADT for a median of 2 years (range 3 months to >10 years) pre-scan. The time on ADT did not influence detection; the detection rates were 89% for patients who had received ADT for <1 year, 63% for a treatment period of 1−<2 years, 83% for 2−4 years, 78% for >4−10 years, and 67% for a treatment period of >10 years. Conclusion: 18F-fluciclovine detected recurrent or metastatic lesions in 82% of patients with prostate cancer receiving ADT. The rates achieved in the present study are consistent with widely reported data for 18F-fluciclovine PET/CT, suggesting that withdrawal of ADT before scanning is not necessary.
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Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Humanos , Masculino , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Noninvasive molecular imaging using peptides and biomolecules labelled with positron emitters has become important for detection of cancer and other diseases with PET (positron emission tomography). The positron emitting radionuclide fluorine-18 is widely available in high yield from cyclotrons and has favorable decay (t1/2 109.7 min) and imaging properties. 18F-Labelling of biomolecules and peptides for use as radiotracers is customarily achieved in a two-step approach, which can be challenging to automate. 6-[18F]Fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ester ([18F]F-Py-TFP) is a versatile 18F-prosthetic group for this purpose, which can be rapidly be produced in an one-step approach on solid support. This work details an automated procedure on the cassette-based GE FASTlab™ platform for the labeling of a peptidomimetic, exemplified by the case of using the Glu-CO-Lys motif to produce [18F]DCFPyL, a ligand targeting the prostate specific membrane antigen (PSMA). RESULTS: From fluorine-18 delivery a fully automated two-step radiosynthesis of [18F]DCFPyL was completed in 56 min with an overall end of synthesis yield as high as 37% using solid phase extraction (SPE) purification on the GE FASTlab™ platform. CONCLUSIONS: Putatively, this radiolabeling methodology is inherently amenable to automation with a diverse set of synthesis modules, and it should generalize for production of a broad spectrum of biomolecule-based radiotracers for use in PET imaging.
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BACKGROUND: The alpha(v)beta(3) integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the alpha(v)beta(3) integrin with (99m)Tc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. PURPOSE: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the alpha(v)beta(3)-avid imaging agent (99m)Tc-NC100692 in patients with breast or lung cancer, and to assess its safety profile. MATERIAL AND METHODS: Twenty-five patients--15 with lung cancer and 10 with breast cancer--were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10-15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq (99m)Tc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. RESULTS: In patients with breast cancer, (99m)Tc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. CONCLUSION: Scintigraphy with (99m)Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of (99m)Tc-NC100692 is safe and well tolerated.
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Neoplasias de la Mama/patología , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia/diagnóstico por imagen , Compuestos de Organotecnecio , Péptidos Cíclicos , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Europa (Continente) , Estudios de Factibilidad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Estados UnidosRESUMEN
BACKGROUND: Neuroendocrine tumours constitute a small group of malignancies; about 200 new patients are diagnosed in Norway annually. This article discusses problems associated with use of deoxyfluoroglucose (FDG) Positron Emission Tomography (PET) and other available options in patients with these conditions, as well as challenges related to introduction of new radiopharmaceutical agents. MATERIAL AND METHODS: The article is based on review of literature in connection with development of new guidelines for nuclear medicine examinations, supplemented with literature identified through a non-systematic search of Pubmed. RESULTS: A large proportion of these tumours grow slowly, and recent data show that 5-year survival is about 50 %. Neuroendocrine tumours are characterised by specific biochemical processes that enable tailoring of radiopharmaceutical agents for PET and consequently a more accurate diagnosis and improved follow-up of these patients. INTERPRETATION: As for other cancer types, diagnostics and detection of metastases are an important factor for correct treatment of neuroendocrine tumours. PET with FDG is of limited use for patients with this condition. New specific radiopharmaceutical agents for PET may imply detection of 90 % of all such tumours.
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Tumores Neuroendocrinos/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Células APUD/metabolismo , Control de Medicamentos y Narcóticos , Fluorodesoxiglucosa F18 , Humanos , Tumores Neuroendocrinos/secundario , Noruega , Radiofármacos , Receptores de Somatostatina/metabolismo , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To retrospectively investigate the uptake of F-fluciclovine on PET/CT in patients with suspected recurrent high-grade glioma (HGG). METHODS: Twenty-one patients were included. The standard of truth was histopathologic interpretation if available. When histopathology was not available or rebiopsy did not show signs of malignancy, clinical follow-up including MRI and clinical outcome was considered the standard of truth. RESULTS: All 21 patients met the reference standard of either histopathologic proof of HGG recurrence (n = 10) or disease progression clinically and with tumor growth corresponding to the primary tumor sites on follow-up MRI (n = 11). Median time from PET/CT to death was 5 months (range, 1-20 months). Median time from primary diagnosis to death was 14.5 months (range, 6 to >400). Average SUVmax of the lesions was 8.3 ± 5.3 (SD) and 0.34 ± 0.13 for normal brain tissue. Median lesion-to-background ratio was 21.6 (range, 3.1-84.4). In 4 patients, F-fluciclovine PET/CT detected small satellite tumors that had not been reported on MR. CONCLUSIONS: The uptake of F-fluciclovine in clinically and/or histopathologically confirmed recurrent HGG is high compared with the uptake reported for other amino acid PET tracers. Because of the high tumor uptake and thus high tracer contrast, small satellite tumors with a diameter below usual reported PET spatial resolution and not reported on MRI were detected in 4 patients. As no patients with confirmed treatment-related changes were included, we cannot as of yet ascertain the ability of F-fluciclovine PET to discriminate between recurrent HGG and treatment-related changes, for example, pseudoprogression and radionecrosis.
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Ácidos Carboxílicos , Ciclobutanos , Glioma/diagnóstico por imagen , Glioma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasia Residual , Recurrencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: Integrin scintimammography with NC100692 and a dedicated gamma-camera, LumaGEM, based on semi-conductor technology, was performed to investigate the detection ability of this combination in breast cancer. METHODS: Eight patients with a high suspicion of breast cancer were administered 600-750 MBq (99m)Tc-labelled NC100629. Two acquisitions using a cranio-caudal and a lateral view were used, with moderate compression of the breast. RESULTS: LumaGEM scintigraphy revealed 9 of 11 malignancies, sized 6-20 mm. Two lesions in patients with multicentric disease were not diagnosed, one of which measured only 2.5 mm. In one patient, the procedure was inconclusive, due to major breast hypertrophy. CONCLUSION: The combined use of NC100629 and a dedicated gamma-camera for breast imaging was highly effective in diagnosing breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Mama/diagnóstico por imagen , Cámaras gamma , Integrina alfaVbeta3/metabolismo , Compuestos de Organotecnecio , Péptidos Cíclicos , Anciano , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Neovascularización Patológica/diagnóstico por imagen , Compuestos de Organotecnecio/metabolismo , Péptidos Cíclicos/metabolismo , CintigrafíaRESUMEN
BACKGROUND: Glucose metabolism can be studied in vitro by a variety of means, also by fluorodeoxyglucose (FDG). As an example of the potential use we have compared the high glucose consumption in cancer cells and in transformed non-malignant foetal cells. The high glucose metabolism in cancer cells is not primarily for the production of energy, a large proportion is transformed to lactate only, producing two instead of potentially 32 ATP equivalents. The secreted lactate reduces the pH in the local microenvironment and gives malignant cells, more apt to thrive in hypoxic and acid environments, a competitive advantage. PURPOSE: To demonstrate the use of FDG in head-to-head comparison of glucose uptake and lactate production in a highly malignant and a highly proliferative non-malignant cell line. MATERIALS AND METHODS: Cell cultures of a foetal kidney cell line and a triple negative breast cancer cell line were incubated with FDG for one hour, washed, harvested and the radioactivity content in the cells was measured in a well counter. The lactate concentration was measured in conditioned medium. RESULTS: The FDG uptake was consistently higher in the non-malignant foetal cell line. The levels of lactate in the conditioned medium were similar. CONCLUSION: Quantitative comparison of glucose metabolism by in vitro use of FDG is a practical, cheap and rapid method. Some foetal cells have higher glucose uptake and produce as much lactate as this highly malignant cell line. This is an argument against the high glucose consumption being related solely to malignancy.
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Metabolismo Energético , Fluorodesoxiglucosa F18/metabolismo , Riñón/metabolismo , Radiofármacos/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , Proliferación Celular , Medios de Cultivo Condicionados/metabolismo , Femenino , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Riñón/embriología , Ácido Láctico/metabolismo , Factores de Tiempo , Neoplasias de la Mama Triple Negativas/patología , Hipoxia Tumoral , Microambiente TumoralRESUMEN
177Lu-lilotomab satetraxetan is a novel antibody-radionuclide conjugate currently in a phase 1/2a first-in-humans dose escalation trial for patients with relapsed CD37-positive indolent non-Hodgkin lymphoma. The aim of this study was to investigate biodistribution and absorbed doses to organs at risk. Methods: In total, 7 patients treated with 177Lu-lilotomab satetraxetan were included for dosimetry. Patients were grouped on the basis of 2 different predosing regimens (with and without predosing with 40 mg of lilotomab) and were treated with different levels of activity per body weight (10, 15, and 20 MBq/kg). All patients were pretreated with rituximab. Serial planar and SPECT/CT images were used to determine time-activity curves and patient-specific masses for organs with 177Lu-lilotomab satetraxetan uptake. Doses were calculated with OLINDA/EXM. Results: The organs (other than red bone marrow and tumors) with distinct uptake of 177Lu-lilotomab satetraxetan were the liver, spleen, and kidneys. The highest uptake was found in the spleen, with doses ranging from 1.54 to 3.60 mGy/MBq. The liver received 0.70-1.15 mGy/MBq. The kidneys received the lowest dose of the source organs investigated, 0.16-0.79 mGy/MBq. No statistically significant differences in soft-tissue absorbed doses were found between the two predosing regimens. The whole-body dose ranged from 0.08 to 0.17 mGy/MBq. Conclusion: The biodistribution study for patients treated with 177Lu-lilotomab satetraxetan revealed the highest physiologic uptake to be in the liver and spleen (besides the red marrow). For all treatment levels investigated, the absorbed doses were found to be modest when compared with commonly assumed tolerance limits.
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Anticuerpos Monoclonales/uso terapéutico , Inmunoconjugados/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/farmacocinética , Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/radioterapia , Masculino , Órganos en Riesgo/efectos de la radiación , Dosis de Radiación , Radiometría , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Distribución TisularRESUMEN
177Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate currently tested in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this work was to develop dosimetric methods and calculate tumor-absorbed radiation doses for patients treated with 177Lu-lilotomab satetraxetan. METHODS: Patients were treated at escalating injected activities (10, 15 and 20 MBq/kg) of 177Lu-lilotomab satetraxetan and with different predosing, with or without 40 mg of unlabeled lilotomab. Eight patients were included for the tumor dosimetry study. Tumor radioactivity concentrations were calculated from SPECT acquisitions at multiple time points, and tumor masses were delineated from corresponding CT scans. Tumor-absorbed doses were then calculated using the OLINDA sphere model. To perform voxel dosimetry, the SPECT/CT data and an in-house-developed MATLAB program were combined to investigate the dose rate homogeneity. RESULTS: Twenty-six tumors in 8 patients were ascribed a mean tumor-absorbed dose. Absorbed doses ranged from 75 to 794 cGy, with a median of 264 cGy across different dosage levels and different predosing. A significant correlation between the dosage level and tumor-absorbed dose was found. Twenty-one tumors were included for voxel dosimetry and parameters describing dose-volume coverage calculated. The investigation of intratumor voxel doses indicates that mean tumor dose is correlated to these parameters. CONCLUSION: Tumor-absorbed doses for patients treated with 177Lu-lilotomab satetraxetan are comparable to doses reported for other radioimmunotherapy compounds. Although the intertumor variability was considerable, a correlation between tumor dose and patient dosage level was found. Our results indicate that mean dose may be used as the sole dosimetric parameter on the lesion level.
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Absorción de Radiación , Anticuerpos Monoclonales/administración & dosificación , Lutecio/administración & dosificación , Linfoma no Hodgkin/radioterapia , Radioisótopos/administración & dosificación , Tetraspaninas/antagonistas & inhibidores , Adulto , Antígenos de Neoplasias , Femenino , Humanos , Linfoma no Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Radiofármacos/administración & dosificación , Dosificación Radioterapéutica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
UNLABELLED: The present study was a proof-of-concept study to provide an initial indication of the efficacy and safety of imaging malignant breast tumors using (99m)Tc-NC100692. The agent is a small peptide with high affinity for integrin receptors that are upregulated and expressed preferentially on proliferating endothelial cells. METHODS: Sixteen patients with suggestive mammographic findings and 4 patients with benign lesions were included. The "standard of truth" was based on the histopathologic diagnosis of the recruited patients. All subjects received up to 75 microg of (99m)Tc-NC100692 with an average (99m)Tc activity of 694 MBq (range, 561-747 MBq). Safety endpoints were treatment-emergent adverse events (AEs) and changes in a limited physical examination, electrocardiogram (ECG) recordings, blood biochemistry, hematology, coagulation, vital signs, and urine analysis after administration of (99m)Tc-NC100692 and throughout the 24-h follow-up. Static images and SPECT were acquired between 40 min and 2.5 h after injection of the agent. Two experienced nuclear medicine physicians read the images in a nonblinded fashion. RESULTS: Nineteen of 22 malignant lesions were detected using (99m)Tc-NC100692 scintigraphy. Twenty lesions confirmed as malignant by histopathology were seen on mammography or ultrasound. Two additional lesions were identified from histopathology alone. Safety parameters evaluated through the follow-up period of 2.5 h included clinical laboratory tests, vital signs, and ECG. Five of 20 subjects experienced nonserious AEs, and all AEs were classified as mild. One subject experienced an AE (dysgeusia) possibly related to administration of (99m)Tc-NC100692. This AE was mild and lasted only for a few minutes. No deaths, serious AEs, or withdrawals due to AEs occurred during the study. CONCLUSION: Nineteen of 22 malignant lesions (86%) were clearly detected via scintigraphic imaging after administration of (99m)Tc-NC100692. Overall, the efficacy data in subjects with suspected breast lesions suggest that (99m)Tc-NC100692 scintigraphy may be effective in detecting malignant lesions. The use of (99m)Tc-NC100692 in subjects with breast cancer is safe and well tolerated. Further studies are warranted to assess the clinical potential of (99m)Tc-NC100692.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Integrina alfaVbeta3/metabolismo , Proteínas de Neoplasias/metabolismo , Compuestos de Organotecnecio/farmacocinética , Péptidos Cíclicos/farmacocinética , Adulto , Anciano , Neoplasias de la Mama/irrigación sanguínea , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/metabolismo , Proyectos Piloto , Cintigrafía , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Internal radiotherapy requires the localization of the radionuclide to the site of action. A new injectable alginate gel formulation intended to undergo immediate gelation in tissues and capable of encapsulating radioactive particles containing 90Y was investigated. METHODS: The formulation was injected intramuscularly, into the bone marrow compartment of the femur and intravenously, respectively, in pigs. The distribution of radioactivity in various tissues was determined. RESULTS: Following intramuscular injection, more than 90% of the radioactivity was found at the site of injection. Following injection into bone marrow, 30-40% of the radioactivity was retained at the site of injection, but a considerable amount of radioactivity was also detected in the lungs (35-45%) and the liver (5-18%). Following intravenous injection, 80-90% of the radioactivity was found in the lungs. CONCLUSION: The present formulation appears suitable for localized radiotherapy in organs and tissues having low perfusion.