Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers.

PURPOSE: Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) have been associated with the aggressive nature of head and neck cancers (HNCs). These tumours grow diffusely, leading to extremely challenging differentiation between tumour and healthy tissue. This analysis aims to introduce a novel approach of tumour detection, contouring and targeted radiotherapy of HNCs using visualisation of CAFs: PET-CT with 68Ga-radiolabeled inhibitors of FAP (FAPI). METHODS: FAPI PET-CT was performed without complications prior to radiotherapy in addition to contrast enhanced CT (CE-CT) and MRI on 14 patients with HNC. First, for tissue biodistribution analysis, volumes of interest were defined to quantify SUVmean and SUVmax in tumour and healthy parenchyma. Secondly, using four thresholds of three-, five-, seven- and tenfold increase of FAPI enhancement in the tumour as compared with normal tissue, four different gross tumour volumes (FAPI-GTV) were created automatically. These were compared with GTVs created conventionally with CE-CT and MRI (CT-GTV). RESULTS: The biodistribution analysis revealed high FAPI avidity within tumorous lesions (e.g. primary tumours, SUVmax 14.62 ± 4.44; SUVmean 7.41 ± 2.39). In contrast, low background uptake was measured in healthy tissues of the head and neck region (e.g. salivary glands: SUVmax 1.76 ± 0.31; SUVmean 1.23 ± 0.28). Considering radiation planning, CT-GTV was of 27.3 ml, whereas contouring with FAPI resulted in significantly different GTVs of 67.7 ml (FAPI × 3, p = 0.0134), 22.1 ml (FAPI × 5, p = 0.0419), 7.6 ml (FAPI × 7, p = 0.0001) and 2.3 ml (FAPI × 10, p = 0.0001). Taking these significant disparities between the GTVs into consideration, we merged FAPI-GTVs with CT-GTVs. This resulted in median volumes, that were, as compared to CT-GTVs, significantly larger with FAPI × 3 (54.7 ml, + 200.5% relative increase, p = 0.0005) and FAPI × 5 (15.0 ml, + 54.9%, p = 0.0122). Furthermore, FAPI-GTVs were not covered by CE-CT-based planning target volumes (CT-PTVs) in several cases. CONCLUSION: We present first evidence of diagnostic and therapeutic potential of FAPI ligands in head and neck cancer. Larger studies with histopathological correlation are required to validate our findings.

Inherently Radiopaque Narrow-Size-Calibrated Microspheres: Proof of Principle in a Pig Embolization Model.

PURPOSE: To investigate radiopacity, size and size calibration, morphology, and vascular distribution of inherently radiopaque microspheres in vitro and in a pig embolization model. MATERIALS AND METHODS: We compared three types of microspheres: DCBead™ (size 100-300 µm) and Embozene™ (250 µm) as clinically established microspheres, and the prototype Visible (250 µm) that contains additional radiopaque material. Size and size calibration of microspheres were examined by laser diffraction. Pulmonary artery embolization was performed in 12 pigs, and radiopacity was examined by in vitro micro-computed tomography (CT), in vivo cone-beam CT, and ex vivo micro-CT after killing. Morphology and vascular distribution of microspheres were microscopically examined. RESULTS: In in vitro and ex vivo micro-CT, radiopacity of Visible was higher than that of Embozene™, whereas DCBead™ showed no radiopacity. In in vivo cone-beam CT, radiopacity was observed with Visible but not with Embozene™ and DCBead™. Laser diffraction revealed that 7.0% (Visible), 6.5% (Embozene™), and 22.5% (DCBead™) of microspheres were smaller than 223.5 µm. Visible and Embozene™ microspheres were very often located in bronchiolus-associated arteries, but rarely in subsegmental and capillary arteries, whereas DCBead™ were very often and often detected in bronchiolus-associated arteries and capillary arteries, respectively (and rarely in subsegmental arteries). CONCLUSION: After pulmonary artery embolization, Visible but not Embozene™ or DCBead™ provide in vivo radiopacity in cone-beam CT. In contrast to non-narrow-size-calibrated DCBead™, pulmonary artery embolization with narrow-size-calibrated Visible and Embozene™ result in a predictable arterial distribution without embolization-related hemorrhagic lung infarction.

Contrast-enhanced ultrasound monitoring of perfusion changes in hepatic neuroendocrine metastases after systemic versus selective arterial 177Lu/90Y-DOTATOC and 213Bi-DOTATOC radiopeptide therapy.

AIM: Radiopeptide therapy with beta emitter labeled (177)Lu/(90)Y- DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC) and more recently also alpha emitting (213)Bi-DOTATOC are promising new treatments for neuroendocrine tumors. No early predictors for treatment response have been recognized and tumor-shrinkage after radiation therapy appears slowly. In some solid tumors a decline in tumor perfusion was found predictive of final treatment response but the gold standard multiphase computed tomography (CT) has a high radiation burden. Therefore we evaluated the ability of contrast-enhanced ultrasound (CEUS) to evaluate tumor perfusion as a response criteria. MATERIALS AND METHODS: 14 patients with hepatic neuroendocrine tumor (NET) metastases were enrolled in the retrospective study. Eleven patients were treated with beta-emitting (177)Lu/(90)Y-DOTATOC, either intravenous (i.v.) (n = 5) or intra-arterial (i.a.) (n = 6) and three patients received alpha-emitting (213)Bi-DOTATOC (i.a.). CEUS and contrast-enhanced CT (CE-CT) were performed before and 3 months after treatment. RESULTS: CE-CT and CEUS presented comparable results in the baseline study and in the assessment of perfusion changes due to the different treatment regimes. A therapy related decrease in tumor perfusion is an early predictor of longterm morphologic response. CONCLUSION: CEUS is available and radiation free technique which showed comparable results for perfusion and diameter of liver metastases compared to CE-CT. Intensity reduction in an arterial phase CEUS can be seen as a positive sign indicating long term tumor response to treatment. Therefore CEUS may be considered as an imaging modality for monitoring early treatment after focal alpha and beta targeted therapy.

[Symptomatic foot shortening with subacute soft tissue swelling of the right tibia]. / Symptomatische Fußverkürzung mit subkutaner Weichteilschwellung am rechten Schienbein.

A 13-year-old girl presented with load-dependent pain of the medial part of the right foot. The medical history revealed no trauma and no sports-related injury. X-ray examinations of the foot and lower leg showed subcortical increased sclerosis at the medial part of the tibia, the medial tarsal bones and of a bunion. Magnetic resonance imaging revealed corresponding findings with localized edema of the bone marrow within the increased subcortical sclerosis but no indications of subcutaneous fibrosis. The constellation is indicative of melorheostosis, a rare benign sclerosis of bones and soft tissue. Subcutaneous fibrosis and limb shortening are also common.