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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.
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
8.
Eur Arch Psychiatry Clin Neurosci ; 265(1): 67-72, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25193677

RESUMO

Thyroid diseases are often associated with psychiatric disorders. The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 %. A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients. Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included. In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed. The proportion of pathologically increased anti-TPO levels in patients with depression was high. Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (χ (2) = 5.5; p = 0.019) different between patients with depression (32.7 %) and patients with schizophrenia (5.3 %). In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 1.2-85.3) when compared with schizophrenia patients. TSH basal level did not differ between patients with depression and patients with schizophrenia. Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression. It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity.


Assuntos
Transtorno Bipolar/complicações , Transtorno Depressivo/complicações , Esquizofrenia/complicações , Tireoidite Autoimune/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Transtorno Bipolar/sangue , Transtorno Depressivo/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/sangue , Tireoidite Autoimune/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
10.
Eur J Nucl Med Mol Imaging ; 42(2): 231-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25316295

RESUMO

PURPOSE: To retrospectively study the influence of nodal tumour burden on lymphoscintigraphic imaging in 509 consecutive patients with melanomas. METHODS: Bidirectional lymphatic drainage, the clear depiction of an afferent lymphatic vessel, time to depiction of the first sentinel lymph node (SLN) and number of depicted and excised nodes were recorded. Nodal tumour load was classified as SLN-negative, SLN micrometastases or macrometastases. RESULTS: In the overall population, using multivariate regression analysis, a short SLN depiction time was significantly associated with the depiction of a greater number of radioactive nodes, a short distance between the primary tumour site and the nodal basin, younger age and lower nodal tumour burden. The proportion of patients with clear depiction of an afferent lymphatic vessel depended on the nodal tumour load (46% in SLN-negative patients, 57% in SLN positive patients, and 69% in patients with macrometastases; P = 0.009). Macrometastasis was significantly associated with delayed depiction of the first radioactive node and a greater number of depicted hotspots. In patients with clinically nonsuspicious nodes, i.e. the classical target group for SLN biopsy, clear depiction of an afferent vessel was significantly associated with a higher number of SLNs during dynamic acquisition, SLN micrometastasis and a higher overall number of metastatic lymph nodes after SLN biopsy plus completion lymphadenectomy. The excision of more than two SLNs did not increase the metastasis detection rate. In patients with bidirectional or tridirectional lymphatic drainage, the SLN positivity rates for the first, second and third basin were 25.4%, 11.7% and 0.0 %, respectively (P = 0.002). CONCLUSION: In patients with clinically nonsuspicious lymph nodes, clear depiction of an afferent lymph vessel may be a sign of micrometastasis. Macrometastasis is associated with prominent afferent vessels, delayed depiction of the first radioactive node and a higher number of depicted hotspots.


Assuntos
Linfocintigrafia , Melanoma/diagnóstico por imagem , Carga Tumoral , Adulto , Idoso , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Agregado de Albumina Marcado com Tecnécio Tc 99m
11.
Ann Surg Oncol ; 20(5): 1714-21, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23314605

RESUMO

BACKGROUND: The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins. PATIENTS AND METHODS: Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive. RESULTS: A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases. CONCLUSION: In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed.


Assuntos
Excisão de Linfonodo/métodos , Linfonodos/diagnóstico por imagem , Linfocintigrafia , Melanoma/diagnóstico por imagem , Melanoma/secundário , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgia , Adulto Jovem
12.
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
13.
Ann Hematol ; 90(11): 1307-15, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21360108

RESUMO

A phase II trial evaluated safety, feasibility and efficacy of a sequential tandem approach combining myeloablative BEAM chemotherapy and autologous stem cell transplantation (ASCT) with myeloablative radioimmunotherapy (HD-RIT), with (131)I-anti-CD20 antibody ((131)I-rituximab), followed by a second ASCT in patients with relapsed or refractory CD20+ B-cell lymphoma. According to protocol, 16 patients with relapsed (n = 14) and refractory (n = 2) CD20+ B-cell lymphoma received salvage therapy with rituximab and Dexa-BEAM, followed by BEAM (HD chemotherapy) and high-dose myeloablative radioimmunotherapy 2-6 months after BEAM. Nine of 16 patients received HD-RIT; seven patients were excluded before HD-RIT because of toxicity or progressive disease. Disease histologies were follicular lymphoma (FL) grades 1 and 2 (n = 4), transformed follicular (FL 3b; n = 6), diffuse large B-cell (DLBCL; n = 4), mantle cell (n = 1) and marginal zone lymphoma (n = 1). After a median follow-up of 50.4 months for OS and 39.7 months for progression-free survival (PFS), estimated 4-year OS and PFS were 67% and 64%, respectively. The estimated 4-year OS and PFS for patients with FL were 80% and 78%, respectively. Toxicity was significant, including one fatal outcome due to pneumonitis. Tandem transplants consisting of HD chemotherapy followed by HD-RIT with (131)I-coupled anti-CD20 are manageable and effective but toxic treatment modalities for relapsed poor prognosis CD20+ B-NHL.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma de Células B/prevenção & controle , Linfoma de Células B/terapia , Radioimunoterapia/métodos , Terapia de Salvação , Transplante de Células-Tronco , Antígenos CD20/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica , Carmustina , Terapia Combinada , Citarabina , Dexametasona , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Etoposídeo , Humanos , Radioisótopos do Iodo/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melfalan , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Estudos Prospectivos , Recidiva , Rituximab
14.
Eur J Nucl Med Mol Imaging ; 38(5): 899-910, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21321791

RESUMO

PURPOSE: The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun) with (99m)Tc-labelled white blood cells in patients with peripheral osteomyelitis. METHODS: A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received (99m)Tc-besilesomab and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. RESULTS: The agreement in diagnosis across all three readers between Scintimun and (99m)Tc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun had higher sensitivity than (99m)Tc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). CONCLUSION: Scintimun imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to (99m)Tc-HMPAO-labelled WBCs.


Assuntos
Imunoglobulina G , Leucócitos/diagnóstico por imagem , Osteomielite/sangue , Osteomielite/diagnóstico por imagem , Tecnécio Tc 99m Exametazima , Adulto , Animais , Doença Crônica , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Inflamação/diagnóstico por imagem , Camundongos , Pessoa de Meia-Idade , Cintilografia , Sensibilidade e Especificidade , Tecnécio Tc 99m Exametazima/efeitos adversos , Sinais Vitais
15.
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
16.
J Dtsch Dermatol Ges ; 9(2): 123-7, 2011 Feb.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-21040471

RESUMO

BACKGROUND: The impact of lymphatic drainage to popliteal sentinel lymph nodes (SLNs) has yet to be explored in detail. PATIENTS AND METHODS: We performed lymphoscintigraphy on 663 patients with cutaneous melanomas. The following day sentinel lymphonodectomy was performed. SLNs were studied on serial sections with both histology and immunohistochemistry. RESULTS: 166 patients had a melanoma located on the foot, the lower leg or the knee, i. e., the potential of lymphatic drainage to the popliteal lymph nodes. On lymphoscintigraphy, only 16 patients (9.6 %) showed popliteal SLNs. A popliteal SLN was surgically identified in only 6 of the 16 patients. The reason for the poor identification rate was exhausted radioactivity in the small popliteal nodes the day after lymphoscintigraphy. In 3 cases, popliteal SLN metastasis was diagnosed. All but one patient had an additional drainage to the inguinal lymph nodes; inguinal SLN metastasis was diagnosed in 7 patients. Even all 16 patients showed lymphatic drainage to iliac lymph nodes, metastasis in the pelvis was diagnosed in 4 patients. CONCLUSIONS: Popliteal SLNs are observed in less than 10 % of the patients with melanomas of the distal leg. In the case of suspected popliteal drainage, lymphoscintigraphy should be performed on the day of sentinel lymphonodectomy because the radioactivity of the small and deeply situated popliteal nodes diminishes rapidly. With respect to complete lymphadenectomy, decision-making is difficult since three nodal basins (popliteal, inguinal and iliac) may harbor metastases.


Assuntos
Perna (Membro)/patologia , Linfonodos/patologia , Melanoma/patologia , Melanoma/secundário , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Alemanha/epidemiologia , Humanos , Metástase Linfática , Melanoma/epidemiologia , Prevalência , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade
17.
J Clin Oncol ; 28(23): 3709-16, 2010 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-20625137

RESUMO

PURPOSE: Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS: At the maximum total (90)Y dose of 45 mCi/m(2) (1,665 MBq/m(2)), grade 3 to 4 hematologic toxicities were reversible to grade 1 in patients with less than 25% bone marrow involvement. The overall OR rate and median PFS for all 61 evaluable patients was 62% (CR/CRu, 48%) and 9.5 months, respectively. Patients without prior ASCT obtained high OR rates of 71% (CR/CRu, 55%) across all NHL subtypes and (90)Y doses, even in poor-risk categories (refractory to last anti-CD20-containing regimen, 73% [CR/CRu, 60%]; bulky disease: 71% [CR/CRu, 43%]). Patients with prior ASCT received lower doses, but achieved an OR rate of 41% (CR/CRu, 29%). For patients with follicular lymphoma (FL), OR rates and median PFS increased with total (90)Y-dose, reaching 100% (CR/CRu, 92%) and 24.6 months, respectively, at the highest dose levels (> 30 mCi/m(2) total (90)Y-dose [1,110 MBq/m(2)]). Further, patients with FL refractory to prior anti-CD20-containing regimens achieved 90% (nine of 10 patients) OR and CR/CRu rates and a median PFS of 21.5 months. CONCLUSION: Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Linfoma não Hodgkin/terapia , Radioimunoterapia , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
18.
Langenbecks Arch Surg ; 395(6): 633-41, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20213463

RESUMO

PURPOSE: We evaluated individualized multimodal oncological strategies in patients with bilobular colorectal liver metastases (biCRC-LM) as well as their effect on R0 resection rates, disease-free survival (DFS), and overall survival (OS). METHODS: Between January 2001 and December 2008, 64 patients were assigned to straightforward or two-stage liver resection +/- preoperative 5-fluorouracil (5FU)-based chemotherapy (CTx). Postoperative strategy after R0-resection was either "wait and see" or "adjuvant" therapy (3 cycles of CTx or anti-carcinoembryonic antigen (CEA)-radioimmunotherapy with (131)I-labetuzumab in a dose of 40-50 mCi/m(2)). RESULTS: Forty-three initially unresectable patients received preoperative CTx for downsizing of their biCRC-LM. Straightforward or two-stage liver resection was intended in 40 and 24 patients, respectively. Histopathologically confirmed R0-liver resection could be achieved in 47 patients. Surgical morbidity and mortality rates were 33% and 1.5%, respectively. Postoperatively, 26 patients received anti-cancer therapy (5 x CTx, 21 x anti-CEA-radioimmunotherapy). After R0-liver resection, median OS was significantly better compared to R1/R2 resections followed by palliative 5FU-CTx (38 versus 19 months, p = 0.035). There was no significant difference in DFS (p = 0.650) and OS (p = 0.435) between straightforward and two-stage liver resection. Compared to "wait and see" strategy, the application of postoperative therapy in adjuvant intent was associated with a better OS (p = 0.048). CONCLUSION: Extensive liver resection within multimodal treatment concepts is justified in patients with biCRC-LM when complete resection of all metastases seems to be achievable.


Assuntos
Neoplasias Colorretais/terapia , Neoplasias Hepáticas/terapia , Idoso , Antineoplásicos/administração & dosagem , Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Radioimunoterapia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
19.
Radiol Clin North Am ; 45(4): 719-33, vii-viii, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17706536

RESUMO

This article describes the impact of [(18)F]2-fluoro-2-deoxy-D-glucose (FDG) PET in the diagnosis of non-prosthesis-related orthopedic infections and inflammation. FDG-PET has an excellent sensitivity in the detection of osteomyelitis (OM). Early data indicate that FDG-PET may be more specific than MRI in diagnosing OM. The role of the combination of FDG and PET-CT in the diagnosis of OM is likely to be determined as this combination is used on a routine basis. Early data from studies in rheumatoid arthritis indicate that FDG-PET is highly accurate in early diagnosis and that it provides results comparable to the most advanced conventional techniques.


Assuntos
Fluordesoxiglucose F18 , Osteomielite/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão , Animais , Fluordesoxiglucose F18/farmacocinética , Humanos , Compostos Radiofarmacêuticos/farmacocinética , Recidiva , Sensibilidade e Especificidade , Distribuição Tecidual
20.
Ann Surg Oncol ; 14(9): 2577-90, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17570017

RESUMO

BACKGROUND: We tested whether adjuvant radioimmunotherapy (RAIT) given after R0 resection of liver metastases (LM) of colorectal cancer is safe and can improve survival. Resection of LM from colorectal cancer is the standard of care in this setting, yet two thirds will eventually relapse, and adjuvant systemic chemotherapy has failed to improve survival. METHODS: Twenty-three patients who underwent R0 resection for LM of colorectal cancer received a dose of 40 to 60 mCi/m(2) (131)I-labetuzumab, a humanized monoclonal antibody against carcinoembryonic antigen. Safety (n = 23), disease-free survival, and overall survival (n = 19) were analyzed, and efficacy was then compared retrospectively with a similar contemporaneous group of control patients (n = 19) treated at the same institution during the same time period but without RAIT. RESULTS: At a median follow-up of 91 months (95% confidence interval [CI], 68.0 months to infinity), the median overall survival for RAIT patients was 58.0 months (95% CI, 55.0 months to infinity), versus 31.0 months (95% CI, 26.0 months to infinity) at a 51-month median follow-up for the controls (P = .032). The median disease-free survival for RAIT patients was 18.0 months (95% CI, 11.0-31.0 months), versus 12.0 months (95% CI, 6.5-27.0 months) for the controls (P = .565). Corresponding survival rates (Kaplan-Meier analyses) were estimated to be 94.7% at 1 year, 78.9% at 2 years, 68.4% at 3 years, and 42.1% at 5 years with RAIT and 94.7%, 68.4%, 36.8%, and 15.8%, respectively, for the controls. RAIT was beneficial independently of bilobar involvement, size and number of LM, or resection margins. Transient myelosuppression was the principal adverse effect. CONCLUSIONS: This first evidence of a promising survival advantage of adjuvant RAIT after long-term follow-up of colorectal cancer patients given salvage resection of LM warrants confirmation in a prospective randomized trial.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno Carcinoembrionário/imunologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Estudos de Casos e Controles , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Imunoconjugados/uso terapêutico , Imuno-Histoquímica , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Radioimunoterapia/métodos , Terapia de Salvação , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
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