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2.
J Clin Neurosci ; 83: 146-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33272885

RESUMO

Pineal cysts are a common incidental finding on brain magnetic resonance imaging (MRI) whichfrequently prompts referral to neurosurgery. Currently, a management algorithm for patientswithout hydrocephalus, Parinaud's syndrome, or pineal apoplexy is lacking.We aimed to identifypredictive factors of pineal cyst volume change andsurgical intervention by performing retrospective chart review of 98 patients between 2005 and 2018 diagnosed with pineal cysts gleaned from our Neurosurgery clinical databases.We included patients whose initial and follow-up MRIs were available in our institutional radiology system or whose surgical pathology confirmed pineal cyst after evaluation with an initial MRI. Patients' medical records were queried for presenting symptoms, demographic, management, and pineal cyst measurements. Three dimensions (anterior-posterior, rostral-caudal, transverse) of pineal cyst size were measured and converted to cyst volume (cm3) for analysis. Fifty-five patients (mean age 26.09 ± 14.7 years) with pineal cysts met study criteria. Follow-up ranged from 4 months to 10 years. The indications for MR imaging included headache (81.8%) and vision problems (42%).Forty-eight patients who were observed had a mean volume change of 0.051 ± 0.862 cm [3] and median volume change of 0 cm [3] Patient symptoms, referral source, and age were not associated with changes in volume on follow-up. Aggregated number of symptoms did not differ between operative and observation patients. (p = 0.29). Pineal cyst volumes tend to remain stable over serial MR images, do not reliably correlate with symptoms, and do not typically require long-term follow-up.


Assuntos
Neoplasias Encefálicas , Cistos do Sistema Nervoso Central , Glândula Pineal/patologia , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Cistos do Sistema Nervoso Central/patologia , Cistos do Sistema Nervoso Central/cirurgia , Criança , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Glândula Pineal/cirurgia , Vigilância da População , Estudos Retrospectivos , Conduta Expectante , Adulto Jovem
3.
Pediatr Radiol ; 40 Suppl 1: S43-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20972781

RESUMO

Lipofibromatosis is a rare, benign fibrofatty tumor of childhood. Since the tumor was first characterized in 2000, only a few additional cases have been reported. The classic presentation of lipofibromatosis is a slow-growing mass arising in a distal extremity, with boys more commonly affected than girls. We report a 16-month-old girl who presented with a lipofibromatosis in her left scapular region that increased 30% in size during a 6-week period. Although previous case reports of lipofibromatosis have emphasized immunohistological findings, this paper focuses on imaging findings and discusses the utility of imaging in the differential diagnosis of pediatric soft-tissue tumors.


Assuntos
Lipomatose/diagnóstico , Ombro/diagnóstico por imagem , Ombro/patologia , Neoplasias de Tecidos Moles/diagnóstico , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Ultrassonografia
4.
Cancer Res ; 63(14): 4082-8, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12874010

RESUMO

Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin-releasing peptide (GRP) that binds to GRP receptors (GRPrs) with high affinity and specificity. The GRPr is overexpressed on a variety of human cancer cells, including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to develop (99m)Tc(I)-radiolabled BBN analogues that maintain high specificity for the GRPr in vivo. A preselected synthetic sequence via solid phase peptide synthesis was designed to produce 2,3-diaminopropionic acid (Dpr)-BBN conjugates with the following general structure: Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH(2)). The new BBN constructs were purified by reversed phase high-performance liquid chromatography. Electrospray mass spectrometry was used to characterize the nonmetallated BBN conjugates. Re(I)-BBN conjugates were prepared by the reaction of [Re(Br)(3)(CO)(3)](2-) and Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH(2)) with gentle heating. Electrospray mass spectrometry was used to determine the molecular constitution of the new Re(I) conjugates. The (99m)Tc conjugates were prepared at the tracer level by preconjugation, postlabeling approach from the reaction of [(99m)Tc(H(2)O)(3)(CO)(3)](+) and corresponding ligand. The (99m)Tc and Re(I) conjugates behaved similarly under identical reversed phase high-performance liquid chromatography conditions. Results from in vitro and in vivo models demonstrated the ability of these derivatives to specifically target GRPrs on human, prostate, cancerous PC-3 cells.


Assuntos
Bombesina/análogos & derivados , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/farmacocinética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Receptores da Bombesina/metabolismo , beta-Alanina/análogos & derivados , beta-Alanina/química , Sequência de Aminoácidos , Animais , Bombesina/farmacocinética , Feminino , Humanos , Marcação por Isótopo/métodos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos SCID , Cintilografia , Espectrometria de Massas por Ionização por Electrospray , beta-Alanina/farmacocinética
5.
Anticancer Res ; 23(1A): 63-70, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12680195

RESUMO

BACKGROUND: Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin-releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is over-expressed on a variety of human cancer cells including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to develop a 188Re(I)-radiolabeled BBN analogue that maintains high specificity for the GRPr in vivo. MATERIALS AND METHODS: A preselected synthetic sequence via solid phase peptide synthesis (SPPS) was designed to produce a Dpr-BBN (Dpr = Diaminopropionic acid) conjugate with the following general structure: Dpr-X-Q-W-A-V-G-H-L-M-(NH2), where the spacer group, X = Serylserylserine. The new BBN-construct was purified by reversed phase-HPLC (RP-HPLC). The non-radioactive Re(I)-BBN conjugate was prepared by the reaction of [Re(Br)3(CO)3]2- and Dpr-SSS-bombesin(7-14)NH2 with heating. ES-MS was used to determine the molecular constitution of the non-metallated and metallated Re (I)--conjugates. The 188 Re-conjugate was prepared at the tracer level by the pre-conjugation, postlabeling approach from the reaction of [188Re(H2O)3(CO)3]+ and corresponding ligand. RESULTS: The 188Re- and non-radioactive Re(I)conjugate behaved similarly under identical RP-HPLC conditions. In vitro cell displacement assays showed that the new conjugate has an IC50 value of approximately 1 nM. In vitro cell binding assays showed that the new conjugate is rapidly internalized and exhibits long-term retention, demonstrating the agonistic efficacy of the radiolabel. In vivo targeting of human prostate, PC-3 tumor xenografts indicated uptake and retention of the new radioconjugate for time-point < or = 24 hours. CONCLUSION: Results from in vitro and in vivo models demonstrated the ability of these derivatives to specifically target GRP receptors on human, prostate and cancerous PC-3 cells. This new construct holds potential for the development of a therapeutic entity for the treatment of prostate cancer.


Assuntos
Bombesina/análogos & derivados , Bombesina/síntese química , Bombesina/farmacocinética , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacocinética , Radioisótopos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Receptores da Bombesina/metabolismo , Rênio/química , Animais , Bombesina/metabolismo , Humanos , Marcação por Isótopo/métodos , Masculino , Camundongos , Camundongos SCID , Compostos Organometálicos/metabolismo , Neoplasias da Próstata/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Rênio/metabolismo , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Nucl Med Biol ; 30(2): 101-9, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12623108

RESUMO

Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is over expressed on a variety of human cancer cells including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to identify a BBN analogue that can be radiolabeled with (177)Lu and maintains high specificity for GRPr positive prostate cancer tumors in vivo. A preselected synthetic sequence via solid phase peptide synthesis (SPPS) was designed to produce a DOTA-BBN (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid) conjugate with the following general structure: DOTA-X-Q-W-A-V-G-H-L-M-(NH(2)), where the spacer group, X = omega-NH(2)(CH(2))(7)COOH (8-Aoc). The BBN-construct was purified by reversed phase-HPLC (RP-HPLC). Electrospray Mass Spectrometry (ES-MS) was used to characterize both metallated and non-metallated BBN-conjugates. The new DOTA-conjugate was metallated with (177)Lu(III)Cl(3) or non-radioactive Lu(III)Cl(3). The (177)Lu(III)- and non-radiolabeled Lu(III)-conjugates exhibit the same retention times under identical RP-HPLC conditions. The (177)Lu-DOTA-8-Aoc-BBN[7-14]NH(2) conjugate was found to exhibit optimal pharmacokinetic properties in CF-1 normal mice. In vitro and in vivo models demonstrated the ability of the (177)Lu-DOTA-8-Aoc-BBN[7-14]NH(2) conjugate to specifically target GRP receptors expressed on PC-3 human prostate cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Bombesina/farmacocinética , Fragmentos de Peptídeos/farmacocinética , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Receptores da Bombesina/metabolismo , Animais , Bombesina/sangue , Bombesina/síntese química , Feminino , Humanos , Marcação por Isótopo/métodos , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos ICR , Camundongos SCID , Transplante de Neoplasias , Especificidade de Órgãos , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/síntese química , Neoplasias da Próstata/sangue , Radiometria/métodos , Cintilografia , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Células Tumorais Cultivadas
7.
Bioconjug Chem ; 13(2): 224-31, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11906259

RESUMO

New human Escherichia coli heat-stable peptide (ST(h)) analogues containing a DOTA chelating group were synthesized by sequential and selective formation of disulfides bonds in the peptide. This synthetic approach utilizes three orthogonal thiol-protecting groups, Trt, Acm, and t-Bu, to form three disulfide bonds by successive reactions using 2-PDS, iodine, and silyl chloride-sulfoxide systems. The DOTA-ST(h) conjugates exhibiting high guanylin/guanylate cyclase-C (GC-C) receptor binding affinities were obtained with >98% purity. In vitro competitive binding assays, employing T-84 human colon cancer cells, demonstrated the IC(50) values of <2 nM for GC-C receptor binding suggesting that the new synthetic ST(h) analogues are biologically active. In vitro stability studies of the (111)In-DOTA-Phe(19)-ST(h) conjugate incubated in human serum at 37 degrees C under 5% CO(2) atmosphere revealed that this conjugate is extremely stable with no observable decomposition at 24 h postincubation. HPLC analysis of mouse urine at 1 h pi of the (111)In-DOTA-Phe(19)-ST(h) conjugate showed only about 15% decomposition suggesting that the (111)In-DOTA-Phe(19)-ST(h) conjugate is highly stable, even under in vivo conditions. In vivo pharmacokinetic studies of the (111)In-DOTA-Phe(19)-ST(h) conjugate in T-84 human colon cancer derived xenografts in SCID mice conducted at 1 h pi showed an initial tumor uptake of 2.04 +/- 0.30% ID/g at 1 h pi with efficient clearance from the blood pool (0.23 +/- 0.14% ID/g, 1 h pi) by excretion mainly through the renal/urinary pathway (95.8 +/- 0.2% ID, 1 h pi). High tumor/blood, tumor/muscle, and tumor/liver ratios of approximately 9:1, 68:1, and 26:1, respectively, were achieved at 1 h pi The specific in vitro and in vivo uptake of the radioactivity by human colonic cancer cells highlights the potential of radiometalated-DOTA-ST(h) conjugates as diagnostic/therapeutic radiopharmaceuticals.


Assuntos
Toxinas Bacterianas/síntese química , Toxinas Bacterianas/farmacocinética , Neoplasias do Colo/tratamento farmacológico , Dissulfetos/metabolismo , Enterotoxinas/síntese química , Enterotoxinas/farmacocinética , Escherichia coli/química , Compostos Heterocíclicos com 1 Anel/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Animais , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/uso terapêutico , Ligação Competitiva , Cromatografia Líquida de Alta Pressão , Neoplasias do Colo/metabolismo , Enterotoxinas/metabolismo , Enterotoxinas/uso terapêutico , Proteínas de Escherichia coli , Feminino , Humanos , Radioisótopos de Índio/química , Concentração Inibidora 50 , Camundongos , Camundongos SCID , Estrutura Molecular , Transplante de Neoplasias , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/uso terapêutico , Células Tumorais Cultivadas , Proteína Tumoral 1 Controlada por Tradução
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