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1.
Int. braz. j. urol ; 45(3): 459-467, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012312

RESUMO

ABSTRACT Purpose: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated an increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. Materials and Methods: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. Results: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95μg/l to 0.16μg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the first or the second scan. Conclusion: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.

2.
Int Braz J Urol ; 45(3): 459-467, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30901173

RESUMO

PURPOSE: 68Ga-PSMA PET/CT imaging is a promising modality for the staging of recurrent prostate cancer (PCa). Current evidence suggests limited diagnostic value of the 68Ga-PSMA PET/CT in PSA-levels ≤0.3ng/mL. Experimental data have demonstrated na increase in PSMA-expression in PCa metastases by androgen deprivation in vitro. The aim of the current study was to investigate a possible enhancing effect of PSMA with low-dose androgen deprivation in patients with BCR and low PSA-levels. MATERIALS AND METHODS: Five patients with PCa and BCR, following radical prostatectomy, underwent 68Ga-PSMA PET/CT. A consecutive 68Ga-PSMA PET/CT was performed 6 to 11 days after injection of 80mg of Degarelix (Firmagon®). We recorded PSA and testosterone serum-levels and changes of PSMA-uptake in 68Ga-PSMA PET/CT images. RESULTS: Median PSA prior 68Ga-PSMA PET/CT was 0.27ng/mL. All patients had a decrease in testosterone serum levels from median 2.95µg/l to 0.16µg/l following Degarelix injection. We observed an increase in the standardized uptake value (SUV) in PSMA-positive lymphogenous and osseous lesions in two patients following androgen deprivation. In another two patients, no PSMA positive signals were detected in either the fi rst or the second scan. CONCLUSION: Our preliminary results of this feasibility assessment indicate a possible enhancing effect of PSMA-imaging induced by low-dose ADT. Despite several limitations and the small number of patients, this could be a new approach to improve staging by 68Ga-PSMA PET/CT in PCa patients with BCR after primary therapy. Further prospective studies with larger number of patients are needed to validate our findings.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Glicoproteínas de Membrana , Metástase Neoplásica/diagnóstico por imagem , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Oligopeptídeos/uso terapêutico , Antígeno Prostático Específico/sangue , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo
3.
Nuklearmedizin ; 57(5): 198-203, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30267402

RESUMO

Previous findings of our group showed the chemokine receptor CXCR4 as a suitable target in PET/CT-imaging of axial bone infections, early postoperative osteomyelitis and periprosthetic infections. The aim of this study was to verify specific uptake of 68Ga-Pentixafor in chronic osteomyelitis. METHODS: 29 consecutive patients who underwent 68Ga-Pentixafor-PET/CT with clinically suspected osteomyelitis were evaluated retrospectively. Bone tissues of 6 patients were available and evaluated by immunohistochemical staining for CXCR4 and autoradiography with 68Ga-Pentixafor. Staining was performed with an anti-CXCR4 antibody. In order to detect lymphocytic infiltration and CXCR4-expressing lymphocytes double immunofluorescence with an anti-CD3 and anti-CXCR4 antibody was performed. RESULTS: 68Ga-Pentixafor-PET/ CT was true positive in 16 and true negative in 13 patients. In available bone tissue samples, immunohistochemical staining of CXCR4 expression and autoradiography with 68Ga-Pentixafor was highly positive. Double immunofluorescence was able to detect CXCR4-expressing T-lymphocytes within all bone samples while a control sample of noninfected tibial bone was negative for CXCR4. CONCLUSION: 68Ga-Pentixafor-PET/CT specifically shows CXCR4-expressing immune cells in chronic osteomyelitis and is therefore a suitable method for imaging chronic infection of the skeleton.Der Chemokinrezeptor CXCR4 konnte in einer Pilotstudie unserer Arbeitsgruppe als geeignete Zielstruktur zur PET/CT-Bildgebung von frühen postoperativen und periprothetischen Osteomyelitiden sowie Osteomyelitiden im Stammskelett identifiziert werden. In dieser Studie haben wir untersucht, ob 68Ga-Pentixafor spezifisch CXCR4-exprimierende Entzündungszellen in einer chronischen Osteomyelitis darstellen kann. METHODEN: Es erfolgte eine retrospektive Auswertung von 29 Patienten mit klinischem Verdacht einer chronischen Osteomyelitis, die mittels 68Ga-Pentixafor-PET/CT untersucht wurden. Hiervon lagen uns in 6 Fällen Knochengewebe zur immunhistochemischen und autoradiographischen Evaluation vor. Die Immunhistochemie wurde mit einem anti-CXCR4 Antikörper durchgeführt. Des Weiteren wurden ein anti-CD3 und der anti-CXCR4-Antikörper zur Detektion CXCR4-exprimierender Lymphozyten am Ort der Entzündung mittels Doppel- Immunfluoreszenz verwendet. ERGEBNISSE: Die 68Ga-Pentixafor-PET/CT war bei 16 Patienten richtig positiv und bei 13 Patienten richtig negativ. Die Färbungen der verfügbaren Knochenpräparate waren sowohl in der Immunhistochemie als auch in der Autoradiographie deutlich positiv. In der Immunfluoreszenz konnten zudem CXCR4-exprimierende Lymphozyten am Ort der Entzündung in allen Proben nachgewiesen werden. Die Kontrolle eines Präparats einer nicht infizierten distalen Tibia zeigte dagegen keine CXCR4-oder CD3-Expression. FAZIT: Mit der 68Ga-Pentixafor-PET/CT können spezifisch CXCR4-exprimierende Lymphozyten am Ort der Entzündung nachgewiesen werden. Die 68Ga-Pentixafor-PET/CT stellt eine geeignete Methode in der Diagnostik chronischer Osteomyeltiden dar.

4.
J Nucl Med ; 59(2): 320-326, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28729430

RESUMO

Because of its role in infection and inflammatory processes, the chemokine receptor CXCR4 might be a potent target in imaging of infectious and inflammatory diseases. The aim of this pilot study was to determine whether the CXCR4 ligand 68Ga-pentixafor is suitable for imaging chronic infection of the bone. Methods: The study comprised 14 patients with suspected infection of the skeleton who underwent 68Ga-pentixafor PET/CT between April 2015 and February 2017 in our facility. 68Ga-pentixafor PET/CT results were retrospectively evaluated against a histologic, bacteriologic, and clinical standard. The results were also compared with available bone scintigraphy, white blood cell scintigraphy, and 18F-FDG PET/CT results. Results:68Ga-pentixafor PET/CT was positive in 9 of 14 patients. Diagnoses included osteitis or osteomyelitis of peripheral bone, osteomyelitis of the maxilla, and infected endoprostheses. Target-to-background ratios were 5.1-15 (mean, 8.7). Eight of 9 cases were true-positive as confirmed by pathology, bacteriology, or clinical observation. All negative cases were confirmed as true-negative by other imaging modalities and follow-up. Conclusion: Imaging of CXCR4 expression with 68Ga-pentixafor PET/CT appears suitable for diagnosing chronic infection of the skeleton. The findings of this study reveal a possible diagnostic gain in suspected chronic infections that are difficult to diagnose by other imaging modalities.

5.
Cancer ; 123(4): 638-649, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27763687

RESUMO

BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) 131 I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2 per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and 18 F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. RESULTS: After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24). CONCLUSIONS: Repeated RIT with 131 I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of 131 I-labetuzumab is a single administration of 50 millicuries/m2 . Cancer 2017;123:638-649. © 2016 American Cancer Society.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Radioimunoterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígeno Carcinoembrionário/uso terapêutico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Nuklearmedizin ; 55(6): 242-249, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27617327

RESUMO

The diagnostic strategy in patients with fever or inflammation of unknown origin remains a major clinical challenge. The aim of this study was to evaluate the role of 18F-FDG-PET/CT in patients with unexplained elevated C-reactive protein with or without fever. Contribution of 18F-FDG-PET/CT to the final diagnosis was evaluated. In addition we determined whether a differentiation between patients with or without fever is clinically reasonable. PATIENTS, METHODS: We retrospectively analysed 72 consecutive patients with unexplained elevated C-reactive protein levels (above 8mg/l) that underwent 18F-FDG-PET/CT in our facility between 10/2009 and 11/2012. 18F-FDG-PET/CT was considered a so-called diagnostic scan when results decisively led to a final diagnosis and adequate therapy with a response of symptoms was initiated due to the PET/CT result. RESULTS: In 60/72 patients (83%) a final diagnosis was established. Diagnoses included infections (58%), non-infectious inflammatory diseases (29%) and malignancies (8%). 18F-FDG-PET/CT was true positive in 47 cases (65%) and the diagnostic scan in 29 patients (40%). Sensitivity of 18F-FDG-PET/CT was 81% and specificity was 86%. Diagnostics, final diagnoses, 18F-FDG-PET/CT results, SUVmax, C-reactive protein levels and the diagnostic scan did not differ significantly between patients with fever and patients without fever. CONCLUSION: 18F-FDG-PET/CT is a useful method in the diagnostic workup of patients with inflammation of unknown origin. In our series there was no significant difference between patients with or without fever. Regarding 18F-FDG-PET/CT-imaging inflammation of unknown origin and unexplained fever can be joined to one entity.


Assuntos
Proteína C-Reativa/análise , Fluordesoxiglucose F18 , Inflamação/sangue , Inflamação/diagnóstico por imagem , Imagem Multimodal/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
7.
Prostate ; 76(8): 776-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26880517

RESUMO

BACKGROUND: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT. METHODS: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga-PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4-21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Humanos , Masculino , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
8.
PLoS One ; 11(2): e0149776, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26901822

RESUMO

Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fatores de Crescimento Neural/metabolismo , Doença de Parkinson/metabolismo , Animais , Callithrix , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Imagem por Ressonância Magnética , Oxidopamina/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único
9.
Eur J Nucl Med Mol Imaging ; 43(5): 898-905, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26563122

RESUMO

PURPOSE: Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. METHODS: Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. RESULTS: One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. CONCLUSIONS: In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.


Assuntos
Carcinoma/diagnóstico por imagem , Compostos Organometálicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Adulto , Idoso , Ácido Edético/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Oligopeptídeos
10.
PLoS One ; 8(3): e60256, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23555936

RESUMO

BACKGROUND: Previously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy. METHODS AND MATERIALS: Rabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy. RESULTS: The uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca(2+) influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect. CONCLUSIONS: Lidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands.


Assuntos
Raios gama/efeitos adversos , Lidocaína/farmacologia , Agonistas Muscarínicos/farmacologia , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/efeitos da radiação , Animais , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/efeitos da radiação , Coelhos
11.
J Neurosci Methods ; 210(2): 195-201, 2012 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-22827895

RESUMO

Considerable progress has been made in small animal single photon emission computed tomography (SPECT) imaging in the field of Parkinson's disease. In preclinical research, there is an increasing demand for in vivo imaging techniques to apply to animal models. Here, we report the first protocol for dopamine transporter (DAT) SPECT in common marmosets using the radioligand ¹²³I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-{4-iodophenyl}nortropane (¹²³I-FP-CIT). Serial SPECT images were obtained on an upgraded clinical scanner to determine the distribution kinetics of ¹²³I-FP-CIT in the marmoset brain. After intravenous injection of approximately 60 MBq of the radiotracer ¹²³I-FP-CIT, stable and specific striatal uptake was observed for at least 4h. Analysis of plasma samples showed rapid disappearance of the radiotracer from blood plasma within a few minutes after application, with activity declining to 4.1% of the administered activity. Structural magnetic resonance imaging (MRI) at 400 µm resolution provided the details of the underlying anatomy. In a marmoset model of Parkinson's disease, which was generated by unilateral injections of 6-hydroxydopamine (6-OHDA) into the nigro-striatal projection pathway, complete loss of striatal DAT binding in combination with behavioral deficits was observed. The presented study demonstrates that ¹²³I-FP-CIT SPECT is a suitable tool to investigate DAT integrity in preclinical studies on common marmosets.


Assuntos
Encéfalo/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos/farmacocinética , Adrenérgicos/toxicidade , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Mapeamento Encefálico , Callithrix , Relação Dose-Resposta a Droga , Lateralidade Funcional , Imagem por Ressonância Magnética , Masculino , Oxidopamina/toxicidade , Ligação Proteica/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Fatores de Tempo
12.
Int J Radiat Oncol Biol Phys ; 82(4): e623-30, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22245203

RESUMO

PURPOSE: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. METHODS AND MATERIALS: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary gland function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. RESULTS: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. CONCLUSIONS: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands.


Assuntos
Lidocaína/farmacologia , Protetores contra Radiação/farmacologia , Glândulas Salivares/efeitos dos fármacos , Glândulas Salivares/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Feminino , Microscopia Eletrônica de Transmissão , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/efeitos dos fármacos , Glândula Parótida/efeitos da radiação , Glândula Parótida/ultraestrutura , Coelhos , Tolerância a Radiação/efeitos dos fármacos , Cintilografia , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/ultraestrutura , Salivação/efeitos dos fármacos , Salivação/fisiologia , Salivação/efeitos da radiação , Glândula Submandibular/diagnóstico por imagem , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/efeitos da radiação , Ultrassonografia , Xerostomia/etiologia , Xerostomia/prevenção & controle
13.
Nuklearmedizin ; 51(2): 55-64, 2012.
Artigo em Alemão | MEDLINE | ID: mdl-22249368

RESUMO

UNLABELLED: The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. AIM, METHODS: As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. RESULTS: During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. CONCLUSIONS: The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.


Assuntos
Ensaios Clínicos como Assunto/legislação & jurisprudência , Aprovação de Drogas/legislação & jurisprudência , Radioisótopos de Gálio/normas , Radioisótopos de Gálio/uso terapêutico , Peptídeos/normas , Peptídeos/uso terapêutico , Alemanha
14.
Strahlenther Onkol ; 187(2): 120-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21271227

RESUMO

PURPOSE: To date, no valid imaging modality exists for early response prediction to neoadjuvant radiochemotherapy in carcinoembryonic-antigen-(CEA)-expressing rectal cancers (UICC stages II and III). It is hypothesized that the uptake of an anti-CEA antibody is directly related to the number of viable tumor cells and may be quantified by immuno-positron emission tomography (immuno-PET). Therefore, we evaluated a novel pretargeting system using TF2, a humanized bispecific trivalent monoclonal antibody (mAb), directed against CEA and the IMP-288-peptide, a hapten for binding radiometals for imaging. Uptake and kinetics of the pretargeting system were investigated in vitro prior to and after irradiation. METHODS: TF2 was labeled with ¹³¹I and IMP-288 with ¹¹¹InCl3. The colorectal cancer cell lines HT29, SW480, and T84 with known varying CEA expression were incubated (≤ 72 hours) with ¹³¹I-TF2 or the TF2-¹¹¹In-IMP-288 pretargeting system. Parallel cultures were irradiated with 2-10 Gy high-energy photons. Tracer uptake, proliferation, apoptosis, and CEA-RNA expression of cancer cells were investigated. RESULTS: The uptake of tracers was dependent on CEA expression and cell count of the cell lines (uptake/106 cells: 0.3% in HT29, 1.5% in SW480, and 14% in T84, p < 0.001). The TF2-¹¹¹In-IMP-288 pretargeting system showed a higher uptake after 4 and 72 hours compared to (131)I-TF2 in parallel cultures. Only in one cell line (SW480) an increased apoptosis after irradiation could be detected. Irradiation increased dose dependently both the specific uptake of ¹³¹I-TF2 and of the TF2-¹¹¹In-IMP-288 system (4-fold in HT29 and T84 after 10 Gy (72 hours), p < 0.001). These results were CEA-mRNA independent. CONCLUSION: This novel pretargeting system allows the quantitative analysis of CEA-expressing colorectal cancer cells and represents a promising tool for evaluation of tumor cell viability after irradiation.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Neoadjuvante , Anticorpos Biespecíficos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Compostos Heterocíclicos com 1 Anel , Humanos , Técnicas In Vitro , Estadiamento de Neoplasias , Oligopeptídeos , Tomografia por Emissão de Pósitrons/métodos , RNA Neoplásico/genética , Radioterapia de Alta Energia
15.
Strahlenther Onkol ; 186(8): 458-62, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20803287

RESUMO

BACKGROUND AND PURPOSE: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. CASE REPORT: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m(2) cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m(2) cetuximab (cold antibody) were given. Weekly doses of 250 mg/m(2) cetuximab were administered for 3 months. RESULTS: The reference lesion showed enhancement of radiolabeled cetuximab ((123)I-Erbi) on scintigraphy; (123)I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. CONCLUSION: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Barreira Hematoencefálica/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Irradiação Craniana , Radioisótopos do Iodo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Anticorpos Monoclonais Humanizados , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cetuximab , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/diagnóstico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cintilografia , Tomografia Computadorizada de Emissão de Fóton Único
16.
Int J Radiat Oncol Biol Phys ; 75(4): 1226-31, 2009 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-19356858

RESUMO

PURPOSE: Systemic therapies when added to whole brain radiotherapy have failed to improve the survival of patients with multiple brain metastases. The epidermal growth factor receptor antibody cetuximab is an attractive option, if it is able to cross the blood-brain barrier. This might be proven with molecular imaging if the radiolabeled antibody is stable long enough to be effective. This study investigated the stability of radiolabeled cetuximab (Erbitux) ((131)I-Erbi) and potential synergistic effects with radiotherapy in vitro. METHODS AND MATERIALS: Two cell lines were investigated, A431 with numerous epidermal growth factor receptors, and JIMT without epidermal growth factor receptors. We labeled 0.4 mg cetuximab with 50 MBq of [(131)I] iodide. Stability was determined for 72 h. The cell cultures were incubated with (131)I-Erbi or cold cetuximab for 72 h. Uptake and cell proliferation were measured every 24 h after no radiotherapy or irradiation with 2, 4, or 10 Gy. RESULTS: The radiolabeling yield of (131)I-Erbi was always >80%. The radiochemical purity was still 93.6% after 72 h. A431 cells showed a (131)I-Erbi uptake about 100-fold greater than the JIMT controls. After 48 h, the A431 cultures showed significantly decreased proliferation. At 72 h after irradiation, (131)I-Erbi resulted in more pronounced inhibition of cell proliferation than the cold antibody in all radiation dose groups. CONCLUSION: (131)I-Erbi was stable for

Assuntos
Anticorpos Monoclonais/farmacocinética , Barreira Hematoencefálica/metabolismo , Receptores ErbB/metabolismo , Radioisótopos do Iodo/farmacocinética , Anticorpos Monoclonais Humanizados , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/secundário , Linhagem Celular Tumoral , Cetuximab , Terapia Combinada/métodos , Estabilidade de Medicamentos , Humanos , Neoplasias Pulmonares , Traçadores Radioativos , Fatores de Tempo
17.
Eur J Nucl Med Mol Imaging ; 35(6): 1204-12, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18228019

RESUMO

PURPOSE: In radioiodine therapy the "stunning phenomenon" is defined as a reduction of radioiodine uptake after diagnostic application of (131)I. In the current study, we established an in vitro model based on the "Fisher rat thyrocyte cell line no. 5" (FRTL-5) to investigate the stunning. METHODS: TSH-stimulated FRTL-5 cells were incubated with (131)I. Time-dependent (131)I uptake and the viability of FRTL-5 cells were evaluated at 4-144 h after radioiodine application. All data was corrected for number of viable cells, half life and (131)I concentration. Sodium iodide symporter (NIS) and the housekeeping gene (beta-actin, GAPDH) levels were quantified by quantitative polymerase chain reaction (qPCR). Additionally, immunohistochemical staining (IHC) of NIS on the cell membrane was carried out. RESULTS: FRTL-5 monolayer cell cultures showed a specific maximum uptake of (131)I 24-48 h after application. Significantly decreased (131)I uptake values were observed after 72-144 h. The decrease in radioiodine uptake was correlated with decreasing mRNA levels of NIS and housekeeping genes. In parallel, unlike in controls, IHC staining of NIS on FRTL-5 cells declined significantly after (131)I long-term incubation. CONCLUSIONS: It could be demonstrated that during (131)I incubation of FRTL-5 cells, radioiodine uptake decreased significantly. Simultaneously decreasing levels of NIS mRNA and protein expression suggest a NIS-associated mechanism. Since mRNA levels of housekeeping genes decreased, too, the reduced NIS expression might be provoked by a cell cycle arrest. Our investigations recommend the FRTL-5 model as a valuable tool for further molecular biological investigations of the stunning phenomenon.


Assuntos
Ciclo Celular/efeitos da radiação , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/farmacocinética , Transdução de Sinais/efeitos da radiação , Glândula Tireoide/metabolismo , Glândula Tireoide/efeitos da radiação , Animais , Linhagem Celular , Ratos , Ratos Endogâmicos F344
18.
Med Phys ; 33(2): 329-36, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16532937

RESUMO

This study compares the performance and image quality of two gamma camera based PET systems of the first and latest generation. We investigated two dual head coincidence gamma cameras (PRISM 2000XP and AXIS, manufactured in 1997 and 2001 by Picker/Philips) predominantly in accordance with the NEMA NU2-1994 and NU2-2001 protocols. All performance parameters except for spatial resolution and image quality were determined after measuring a standard cylinder over several half-life periods. Scatter and random fractions were evaluated with the sinogram technique. In order to determine spatial resolution and image quality we used phantoms as described in the NEMA NU2-2001 protocol. The efficiency of the new system was found to be increased. True count rate at activity levels used in clinical conditions is improved and scatter fraction is decreased substantially. Accordingly, improved spatial resolution and image quality were observed with the new system. Altogether, the AXIS represents a further approach to the performance of dedicated positron emission tomographs.


Assuntos
Câmaras gama/tendências , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Tomografia Computadorizada de Emissão/métodos , Humanos , Espalhamento de Radiação , Sensibilidade e Especificidade , Tecnologia Radiológica
19.
Strahlenther Onkol ; 182(1): 30-6, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16404518

RESUMO

BACKGROUND: Radioiodine uptake (RIU) is one of the main prognostic factors for curative results of radioiodine therapy in patients with differentiated thyroid cancer. Some days after application of (131)I, the uptake of a subsequent administration of radioiodine was found to be reduced. In contrast, early after irradiation with high-energy photons glucose and amino acid uptake were observed to be increased. Effects of external irradiation on RIU of thyrocytes using high-energy photons have not been investigated so far. MATERIAL AND METHODS: Two different cell lines (FRTL-5 and ML-1 cells) derived from thyroid tissue were studied in vitro. Cell lines were either incubated with (131)I only (controls) or additionally irradiated with single doses of 6 or 10 Gy of high-energy photons using a linear accelerator. Cell number and RIU were determined 24-96 h after (131)I application. RIU measurements were repeated after application of sodium perchlorate in excess to investigate specificity of the uptake. Statistical analyses were performed using non-parametric tests. RESULTS: Incubation with radioiodine as well as irradiation with high-energy photons slowed down proliferation in investigated cell lines significantly. Irradiation with solely (131)I resulted in stable or slightly decreased iodide uptake. Compared to those cells, the RIU increased significantly in externally irradiated cells, i. e., additional irradiation with 10 Gy resulted in an almost threefold increase of RIU in FRTL-5 after 72 h. The increase of RIU after irradiation was dose-dependent in both cell lines and could be blocked by perchlorate excess. CONCLUSION: It could be demonstrated that external irradiation increases RIU in thyroid cell cultures early after irradiation. The increase was dose-dependent and specific, as it could be blocked by perchlorate. This effect appears to be similar to the increase of other actively transported substances after irradiation with high-energy photons. Therefore, the results of this study may contribute to the knowledge of a generalized irradiation-induced mechanism which causes the activation of different cellular transporters. The clinical impact of these findings on combined therapy concepts has to be investigated in further experiments.


Assuntos
Radioisótopos do Iodo/farmacocinética , Glândula Tireoide/metabolismo , Glândula Tireoide/efeitos da radiação , Animais , Contagem de Células , Linhagem Celular , Interpretação Estatística de Dados , Relação Dose-Resposta à Radiação , Humanos , Iodetos/metabolismo , Percloratos/farmacologia , Fótons , Doses de Radiação , Ratos , Compostos de Sódio/farmacologia , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Fatores de Tempo
20.
Eur J Nucl Med Mol Imaging ; 31(3): 403-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14685783

RESUMO

The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10(8) NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/terapia , Imunoterapia Adotiva/métodos , Radioisótopos de Índio , Células Matadoras Naturais/diagnóstico por imagem , Células Matadoras Naturais/transplante , Adulto , Idoso , Carcinoma de Células Renais/imunologia , Sobrevivência Celular , Transplante de Células/métodos , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Pessoa de Meia-Idade , Especificidade de Órgãos , Reação em Cadeia da Polimerase/métodos , Cintilografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Transplante Homólogo/métodos
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