Long-term efficacy and safety of a hyaluronic acid dermal filler based on Tri-Hyal technology on restoration of midface volume.

INTRODUCTION: Art Filler Volume (AFV) is a hyaluronic acid (HA)-based filler formulated with "Tri-Hyal" technology, a unique combination of three sizes of HA chains. This study assessed AFV efficacy and safety over 18 months when used to restore midface volume. METHODS: During this open-label study, a maximum of 1.8 mL AFV was injected into each cheek area on Day 0 (D0). Subjects were evaluated at D21, when, if necessary, a retouch could be performed (maximum 1.2 mL per cheek). Subjects were evaluated at seven follow-up visits through to D540. The primary assessment was based on the evolution of the Medicis Midface Volume Scale (MMVS) grade on D21. Secondary outcomes were local and general adverse events, investigator- and subject-assessed Global Aesthetic Improvement Scale scores and changes in self-esteem. RESULTS: Of the 79 healthy Caucasians enrolled (mean age 54.8 years), 25 required a second injection. In the intention-to-treat population, mean overall MMVS scores improved significantly from D0 (3.2 ± 0.4) to D21 (1.8 ± 0.6) and D42 (1.7 ± 0.6) (all p < 0.0001). MMVS scores for each cheek also improved significantly, irrespective of retouch on D21: 22% of injections showed a persistent benefit at D540 without retouch. The most common adverse events were pain on palpation (19%), erythema (15%) and edema (13%); most were mild or moderate and resolved within 2 weeks. CONCLUSION: AFV produces a sustained objective and subjective midface volume restoration in female and male subjects, often without retouching, and was well tolerated.

Fully automated preparation and conjugation of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) with RGD peptide using a GE FASTlab™ synthesizer.

PURPOSE: The aim of this work was to automate the radiosynthesis of [(18)F]SFB, a widely used reagent for the labeling of biomolecules with (18)F on a new generation commercial synthesis module (FASTLab™, GE Healthcare). PROCEDURES: Two synthesis approaches were implemented on this module: the classical "two-pot radiosynthesis" and the more recently described "one-pot" method. RESULTS: The "two-pot" approach affords [(18)F]SFB with a 42% decay-corrected yield in 57 min (n = 24) with a chemical purity sufficient to avoid an intermediate HPLC purification. The recently established "one-pot" method, afforded a product with a lower chemical purity, in the conditions used in this report. The lower d.c. yield obtained (32% (n = 15)) was related to the low (18)F labeling yields obtained in MeCN compared with DMSO. The subsequent conjugation step with a RGD (PRGD2) peptide was also successfully automated. CONCLUSIONS: The formulated [(18)F]FPRGD2 was obtained without any operator manipulation with a d.c. yield of 13% ± 3% (n = 13) in 130 min, a radiochemical purity >98% and a specific activity of 140 ± 40 TBq/mmol.

General method for labeling siRNA by click chemistry with fluorine-18 for the purpose of PET imaging.

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click-type reaction, was used to label a double-stranded oligonucleotide (siRNA) with fluorine-18. An alkyne solid support CPG for the preparation of monostranded oligonucleotides functionalized with alkyne has been developed. Two complementary azide labeling agents (1-(azidomethyl)-4-[(18)F]fluorobenzene) and 1-azido-4-(3-[(18)F]fluoropropoxy)benzene have been produced with 41% and 35% radiochemical yields (decay-corrected), respectively. After annealing with the complementary strand, the siRNA was directly labeled by click chemistry with [(18)F]fluoroazide to produce the [(18)F]-radiolabeled siRNA with excellent radiochemical yield and purity.

New strategy for the preparation of clickable peptides and labeling with 1-(azidomethyl)-4-[(18)F]-fluorobenzene for PET.

The alkyne-azide Cu(I)-catalyzed Huisgen cycloaddition, a click type reaction was used to label a peptide with fluorine-18. A novel solid phase synthesis approach for the preparation of clickable peptides has been developed and has also permitted the straightforward preparation of reference compounds. A complementary azide labeling agent (1-(azidomethyl)-4-[(18)F]-fluorobenzene) has been produced in a four step procedure in 75 min with a 34% radiochemical yield (decay corrected). Conjugation of [(18)F]fluoroazide with a model alkyne-neuropeptide produced the desired (18)F-radiolabeled peptide in less than 15 min with a yield of 90% and excellent radiochemical purity.

Management of invasive juvenile nasopharyngeal angiofibromas: the role of a multimodality approach.

OBJECTIVE: Juvenile nasopharyngeal angiofibromas involving the cranial base and intracranial compartment are challenging tumors. We reviewed our experience of these tumors and analyzed the efficacy of a multimodality management. METHODS: Between 1981 and 2000, 15 extensive juvenile nasopharyngeal angiofibromas (Fisch Grade III or IV) were treated at our institution. The mean age of the patients was 14.5 years, and the mean interval between the first symptom and diagnosis was 12.9 months. Initial management included preoperative embolization of the external carotid artery feeders, followed by tumor removal. A maxillofacial procedure was performed in eight cases, a combination of maxillofacial and neurosurgical approach was performed in four cases, and a neurosurgical cranial base approach was performed in three cases. RESULTS: Total removal after the initial procedure was obtained in eight patients. Subtotal removal justified additional surgery in one case, gamma knife radiosurgery in two cases, and fractionated irradiation in four cases. True recurrences were observed in four cases at a mean interval of 37 months (range, 24-46 mo) and required tailored multimodality management. No cases of perioperative death were observed. One patient underwent hemiparesis after embolization in the early period of our experience. Permanent facial numbness was reported in four cases, moderate cosmetic problems were reported in three cases, and hyposmia was reported in three cases. Except for one patient who was lost to follow-up at 18 months, 12 patients were free of disease and two patients were free of tumor progression. All patients had normal or near-normal daily life at the last check-up, with a median follow-up period of 108 months (mean, 117 mo; range, 91-252 mo). CONCLUSION: Extensive juvenile nasopharyngeal angiofibromas are efficiently managed with a multimodal protocol in which preoperative embolization is followed by optimal surgical removal using various transcranial or transfacial approaches. Adjunctive gamma knife radiosurgery is a valuable option for intracavernous residual tumor. Our protocol offers long-term cure with acceptable morbidity.

Auto-assembling of ditopic macrocyclic lanthanide chelates with transition-metal ions. Rigid multimetallic high relaxivity contrast agents for magnetic resonance imaging.

PhenHDO3A is a ditopic ligand featuring a tetraazacyclododecane unit substituted by three acetate arms and one 6-hydroxy-5,6-dihydro-1,10-phenanthroline group (PhenHDO3A = rel-10-[(5R,6R)-5,6-dihydro-6-hydroxy-1,10-phenantholin-5-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). This ligand was specially designed so as to obtain highly stable heteropolymetallic assemblies. PhenHDO3A has been prepared starting from phenanthroline epoxide and either a triprotected tetraazacyclododecane or tert-butyl triester of N,N',N' '-tetraazacyclododecane-triacetic acid. The latter yields PhenHDO3A in a single step. PhenHDO3A forms kinetically stable lanthanide complexes (acid-catalyzed kinetic constant kH = (1.2 +/- 0.2) x 10(-3) s(-1) M(-1)) whose solution structure has been deduced from a quantitative analysis of the paramagnetic shifts and the longitudinal relaxation times of the proton nuclei of YbPhenHDO3A. The alcohol group of the dihydro-phenanthroline unit remains coordinated to the encapsulated metal ion despite the steric crowding brought about by this group. Furthermore, the complexes are monohydrated, as shown by luminescence lifetime measurements on EuPhenHDO3A solutions. Relaxivity titrations at 20 MHz clearly indicate that the phenanthroline unit of GdPhenHDO3A is available for the spontaneous formation of highly stable tris complexes with the Fe2+ and Ni2+ ions. The water-exchange times and the rotational correlation times of GdPhenHDO3A and Fe(GdPhenHDO3A)32+ have been deduced from variable temperature 17O NMR studies and from nuclear relaxation dispersion curves. Despite rather slow water-exchange rates (taum0 = 1.0-1.2 x 10(-6) s), relaxivity gains of 90% have been observed upon the formation of the heterometallic tris complexes. The latter rotate about four times more slowly (taur0= 398 ps) than the monomeric unit (taur0 = 105 ps) and their relaxivity is, accordingly, twice as high. The relaxivity of the tris complexes between 10 and 50 MHz is comparable to relaxivities reported for Gd3+-containing dendrimers of much higher molecular weights. The high relaxivity of the tris-PhenHDO3A lanthanide complexes is attributed to their internal rigidity.

Aberrant internal carotid artery in the temporal bone: imaging findings and management.

OBJECTIVES: To describe the clinical and radiological features of the vascular anomaly aberrant internal carotid artery (ICA) in the temporal bone and to discuss management strategies. DESIGN: Retrospective study. PATIENTS: Sixteen cases of aberrant ICA were diagnosed between 1982 and 2003. RESULTS: Of 16 cases, 11 were recognized by imaging assessment, 4 were recognized during middle ear surgery, and 1 was recognized clinically. Among the 11 cases, 8 malformations were diagnosed because of otologic symptoms related to the abnormal ICA or chronic otitis, while the other 3 were identified incidentally because of an underlying accompanying disease. In 4 cases, the diagnosis was made during surgery related to chronic otitis media (n = 2) or conductive hearing loss (n = 2). In these 4 cases, massive bleeding resulted from surgical injury to the vessel. Packing the external auditory canal and the middle ear first controlled the bleeding. Endovascular procedure was required in 2 cases to exclude an aneurysm or to control bleeding but was followed by anterior cerebral stroke in 1 case. The aberrant ICA could be identified on computed tomographic scan by the following features: intratympanic mass, enlarged inferior tympanic canaliculus, absence of the vertical segment of the ICA canal, and absence of bone covering the tympanic portion of the ICA. Conventional angiography was mandatory when intervention was planned to control bleeding or aneurysm. CONCLUSIONS: This study highlights that aberrant ICA has to be identified before any middle ear surgery because misdiagnosis may lead to dramatic surgical complications, whereas diagnosis with computed tomographic scan is easy. Bleeding is a minor complication compared with the putative neurologic deficit due to endovascular occlusion.