Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic ossification (HO) syndrome caused by gain-of-function mutations of bone morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive ossification of skeletal muscles, tendons, ligaments, and joints. In this disease, HO can occur in discrete flares, often triggered by injury or inflammation, or may progress incrementally without identified triggers. Mice harboring an Acvr1 knock-in allele recapitulate the phenotypic spectrum of FOP, including injury-responsive intramuscular HO and spontaneous articular, tendon, and ligament ossification. The cells that drive HO in these diverse tissues can be compartmentalized into two lineages: an Scx tendon-derived progenitor that mediates endochondral HO of ligaments and joints without exogenous injury, and a muscle-resident interstitial Mx1 population that mediates intramuscular, injury-dependent endochondral HO. Expression of Acvr1 in either lineage confers aberrant gain of BMP signaling and chondrogenic differentiation in response to activin A and gives rise to mutation-expressing hypertrophic chondrocytes in HO lesions. Compared to Acvr1, expression of the man-made, ligand-independent ACVR1 mutation accelerates and increases the penetrance of all observed phenotypes, but does not abrogate the need for antecedent injury in muscle HO, demonstrating the need for an injury factor in addition to enhanced BMP signaling. Both injury-dependent intramuscular and spontaneous ligament HO in Acvr1 knock-in mice were effectively controlled by the selective ACVR1 inhibitor LDN-212854. Thus, diverse phenotypes of HO found in FOP are rooted in cell-autonomous effects of dysregulated ACVR1 signaling in nonoverlapping tissue-resident progenitor pools that may be addressed by systemic therapy or by modulating injury-mediated factors involved in their local recruitment.

SNB is a reliable diagnostic staging technique for the clinically negative neck in patients with early-stage (T1-T2, cN0) oral squamous cell carcinoma.

With conventional imaging techniques such as planar lymphoscintigraphy and SPECT/CT, preoperative sentinel node (SN) identification can be difficult when the SN is near the primary tumor, as is the case in floor-of-mouth carcinomas. PET/CT lymphoscintigraphy may improve the detection and localization of such SNs. Methods: In this study, the clinical feasibility of PET/ CT lymphoscintigraphy using 89 Zr-nanocolloidal albumin was evaluated in 5 oral cancer patients. PET/CT lymphoscintigraphy was performed after peritumoral injection of 89 Zr-nanocolloidal albumin. The routine SN procedure, including SPECT/CT using 99m Tc-nanocolloidal albumin, was performed on the same patients 7-9 d after the injection of 89 Zr-nanocolloidal albumin. Results: Comparison of radiocolloid distribution on PET/CT and SPECT/CT showed identical drainage patterns. Moreover, PET/ CT was able to identify additional foci near the primary tumor. Conclusion: This pilot PET/CT study on SN detection indicated that lymphoscintigraphy using 89 Zr-nanocolloidal albumin is feasible.Key Words: sentinel node; PET/CT; 89 Zr; Nanocoll; head and neck cancer J Nucl Med 2013; 54:585-589 DOI: 10.2967/jnumed.112.115188Sent inel nodes (SNs) near a primary tumor can be hidden by the high amount of radioactivity at the injection site. In such cases, the resolution of planar lymphoscintigraphy and SPECT/CT is limited (1). For oral cancer, this is especially true for tumors located in the floor of the mouth that drain to lingual lymph nodes or level I lymph nodes (2,3), which may explain the significantly lower sensitivity of the SN procedure for floor-of-mouth tumors than for other sites in the oral cavity (80% vs. 97%) (4).PET provides dynamic 3-dimensional information at a higher spatial resolution and, thus, improves anatomic localization-of particular importance in the complex anatomy of the neck, with its abundant lymph nodes (i.e., about 150 on each side). In addition, improved visualization of lymphatic vessels may result in better differentiation between first-and second-echelon lymph nodes. Therefore, we hypothesized that PET might perform better than g-camera-based techniques.Recently, we developed 89 Zr-nanocolloidal albumin for lymphatic mapping and SN detection using PET/CT. The potential of this tracer was shown preclinically in a rabbit lymphogenic metastasis model (5).The present study aimed to evaluate the feasibility of PET/ CT lymphoscintigraphy using 89 Zr-nanocolloidal albumin in patients with early-stage oral cavity carcinoma and to obtain initial clinical experience in a head-to-head comparison with g-camera-based imaging using 99m Tc-nanocolloidal albumin. MATERIALS AND METHODS PatientsThe study included 5 previously untreated patients with earlystage oral cancer who were scheduled for transoral excision and the SN procedure. Each patient had a clinically negative neck as assessed by ultrasound-guided fine-needle aspiration cytology. Three of the patients had a paramedian floor-of-mouth carcinoma, and 2 had a lateral tongue carcinoma. Th...

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Results of this study indicate that additional late lymphoscintigraphic imaging should be performed only in selected cases.