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1.
Eur J Nucl Med Mol Imaging ; 51(4): 978-990, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38049658

RESUMEN

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Dominio de Fibronectina del Tipo III , Radioisótopos de Flúor , Neoplasias Pulmonares , Proteínas Recombinantes , Humanos , Ratones , Animales , Antígeno B7-H1/metabolismo , Ligandos , Macaca fascicularis/metabolismo , Tomografía de Emisión de Positrones/métodos , Péptidos/química
2.
Cytotherapy ; 15(5): 571-7, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23415918

RESUMEN

BACKGROUND AIMS: Long-bone pseudoarthrosis is a major orthopedic concern because of numerous factors such as difficulty of the treatment, high recurrence, high costs and the devastating effects on the patients' quality of life, which sometimes ends in amputation. Although the "gold standard" for the treatment of this pathology is autologous bone grafting, which has high osteogenic, osteoconductive and osteoinductive properties, this treatment presents some restrictions such as the limited amount of bone that can be taken from the patient and donor site morbidity. Bone marrow mononuclear cells (BM-MNCs) comprise progenitor and stem cells with pro-angiogenic and pro-osteogenic properties. Allogenic cancellous bone graft is a natural and biodegradable osteoconductive and osteoinductive scaffold. Combination of these two components could mimic the advantages of autologous bone grafting while avoiding its main limitations. METHODS: Long-bone pseudoarthrosis was treated in seven patients with autologous BM-MNCs from iliac crest combined with frozen allogenic cancellous bone graft obtained from the tissue bank. RESULTS: All patients showed complete bone consolidation 5.3 ± 0.9 months (range, 2-9 months) after cell transplantation. Moreover, limb pain disappeared in all of them. The mean follow-up was 35.8 ± 4.6 months after transplantation (range, 24-51 months) without pseudoarthrosis recurrence or pain reappearing. CONCLUSIONS: Combination of autologous BM-MNCs and allogenic bone graft could constitute an easy, safe, inexpensive and efficacious attempt to treat long-bone pseudoarthrosis and non-union by reproducing the beneficial properties of autologous bone grafting while restricting its disadvantages.


Asunto(s)
Trasplante de Médula Ósea , Trasplante Óseo , Seudoartrosis/terapia , Trasplante Homólogo , Adulto , Anciano , Animales , Células de la Médula Ósea/citología , Tratamiento Basado en Trasplante de Células y Tejidos , Femenino , Humanos , Leucocitos Mononucleares/citología , Masculino , Persona de Mediana Edad , Seudoartrosis/patología
3.
Acta Orthop Belg ; 70(5): 435-43, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15587032

RESUMEN

Internal fixation with a Gamma nail, in its short and long versions, is an excellent surgical technique for intertrochanteric and subtrochanteric fractures of the femur. A stable osteosynthesis is obtained which allows early mobilisation and promotes healing of the fracture. However, it is not free from complications; many of them are due to poor surgical technique and/or inadequate monitoring. Breakage due to fatigue of the material is an exceptional complication. A review of 843 cases operated in our department between 1990 and 2002 was made. Five cases of implant breakage were found. Non-union of the fracture appears to be the primary cause. The weakest point of the Gamma nail is the opening for the cervical screw. The optimal treatment will depend on each particular case. The possibility of dynamisation of the construct should be considered when delayed healing is suspected.


Asunto(s)
Tornillos Óseos/efectos adversos , Fracturas del Cuello Femoral/cirugía , Fijación Intramedular de Fracturas/efectos adversos , Fracturas de Cadera/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Remoción de Dispositivos , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Estudios de Seguimiento , Fijación Intramedular de Fracturas/métodos , Fracturas de Cadera/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Pronóstico , Falla de Prótesis , Radiografía , Rango del Movimiento Articular/fisiología , Reoperación , Estudios Retrospectivos , Muestreo , Resultado del Tratamiento
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