Immunoscintigraphy of patients with head and neck carcinomas, with an anti-angiogenetic antibody fragment.

OBJECTIVE: In a phase I/II clinical study, we investigated tumor targeting in patients with head and neck squamous cell carcinomas (SCC), using an antibody directed against the extra-domain-B of fibronectin (EDB), a marker of angiogenesis and tissue remodeling. STUDY DESIGN AND SETTING: Five patients with SCC were injected with the 123-iodine-radiolabeled L19(scFv)2 antibody and underwent scintigraphic detection with single photon emission tomography with computerized tomography (SPECT/CT). In addition, 18F-fluorodeoxyglucose (18FDG) positron emission tomography with computerized tomography (PET/CT) was performed. RESULTS: Successful targeting of the primary tumor could be achieved in 4 of 5 patients and was comparable to PET imaging. No side effects were observed. CONCLUSIONS: Tumor targeting with the L19(scFv)2 antibody is also feasible for head and neck SCC. SIGNIFICANCE: These results may serve as a base for future therapeutical applications in human beings, with modified versions of the L19(scFv)2 antibody, designed to selectively deliver bioactive molecules into malignant tumors.

Kaposiform hemangioendothelioma arising in the ethmoid sinus of an 8-year-old girl with severe epistaxis.

BACKGROUND: Epistaxis is very common during childhood. It occurs primarily in boys and is usually self-limiting. Trauma and nose picking are among the most common causes. In general, epistaxis can be easily treated with anterior nasal packing or electrocoagulation. METHODS: We report a case of an 8-year-old girl with severe unilateral epistaxis. RESULTS: The bleeding originated from a kaposiform hemangioendothelioma arising in the left nasal cavity and ethmoid sinus. The feeding vessels originating from the maxillary artery were first embolized. The tumor was then surgically removed through a combined external ethmoidectomy and endonasal approach. The postoperative course was uneventful. MRI at 6 months after surgery showed no tumor recurrence. CONCLUSIONS: We report a previously undescribed cause of epistaxis in children, namely, a kaposiform hemangioendothelioma. To our knowledge, this is the first such case in the English-language literature. The differential diagnosis of severe unilateral nasal bleeding among the pediatric population should include the possibility of a kaposiform hemangioendothelioma.

Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C.

BACKGROUND: The targeted delivery of bioactive molecules with antibodies specific to tumor-associated antigens represents a promising strategy for improving the efficacy of tumor therapy. The large isoform of tenascin-C, an abundant glycoprotein of the tumor extracellular matrix, is strongly overexpressed in adult tissue undergoing tissue remodeling, including wound healing and neoplasia, and has been implicated in a variety of different cancers while being virtually undetectable in most normal adult tissues. EXPERIMENTAL DESIGN: We have used antibody phage technology to generate good-quality human recombinant antibodies (F16 and P12) specific to the alternatively spliced domains A1 and D of the large isoform of tenascin-C. The tumor-targeting properties of F16 and P12 were assessed by biodistribution studies in tumor xenografts using the antibodies in small immunoprotein (SIP) format. RESULTS: SIP(F16) selectively accumulated at the tumor site with 4.5%ID/g at 24 hours in the U87 glioblastoma model but was rapidly cleared from other organs (tumor-to-organ ratios, approximately 10:1). The accumulation of SIP(P12) in the tumor was lower compared with SIP(F16) and persistent levels of radioactivity were observed in the intestine. CONCLUSIONS: These data suggest that the F16 antibody, specific to domain A1 of tenascin-C, is a promising building block for the development of antibody-based pharmaceuticals in view of its excellent tumor-targeting performance and the strong expression of the antigen in a variety of primary and metastatic tumors.

Expression of the extra domain B of fibronectin, a marker of angiogenesis, in head and neck tumors.

OBJECTIVES/HYPOTHESIS: The extra domain B (ED-B) of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is expressed in the majority of aggressive solid human tumors, whereas it is not detectable in normal vessels and tissues. STUDY DESIGN: In view of the diagnostic and therapeutic clinical applications of the L19 antibody, which is specific for the ED-B domain of fibronectin, a prospective immunohistochemical analysis of different head and neck tumors was performed. METHODS: In all, 82 head and neck tissue biopsy specimens were immunohistochemically analyzed using the L19 antibody. They consisted of 53 different malignant tumors, 8 benign tumors, 10 nontumoral lesions, and 11 normal control tissues. RESULTS: A strong positive staining with the L19 antibody could be observed in 87% of the investigated malignant tumors, in only 38% of the benign tumors, and in 20% of the nontumoral lesions (P <.0001). The extra domain B was completely absent in the normal control tissue samples. CONCLUSIONS: The results show that ED-B is abundantly expressed around the neovasculature and in the stroma of the majority of malignant tumors of the head and neck but is undetectable in normal tissues. The ED-B domain of fibronectin is a good-quality tumor-stroma-associated antigen that warrants clinical trials with antibody-based pharmaceuticals, including immunoscintigraphic investigations and radioimmunoguided surgery with the radiolabeled L19 antibody.

Paraganglioma of the cervical sympathetic trunk.

We report the case of a 17-year-old man who presented with left-sided Horner's syndrome. Magnetic resonance imaging revealed a spindle-shaped cervical tumor in the left paravertebral space. During operation, a tumor originating from the left sympathetic trunk was found. The histopathologic analysis showed a sympathetic paraganglioma. The sympathetic trunk is an extremely rare location for a cervical paraganglioma; only a few cases have been reported in the literature.