Ambros Beer

In this retrospective study we compared magnet resonance imaging (MRI) and computed tomography (CT) each combined with identical 2-deoxy-2-[18F] fluoro-D-glucose or 2-[18F] F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) data in patients with recurrent differentiated thyroid cancer (DTC). In total 42 patients with DTC were examined. All patients underwent FDG PET/MRI and CT, the latter originating from one of the following examinations: I-131 single photon emission computed tomography/CT (32/42), low dose FDG PET/CT (5/42) or diagnostic FDG PET/CT (5/42). Two readers assessed FDG PET/MRI as well as FDG PET/CT, with the latter CT coming from one of the above examinations performed at a maximum temporal interval of 5 days from PET/MRI. Local recurrence, cervical lymph node – and pulmonary metastases were assessed in a consensus read. Lesions rated with a high malignancy score (score 4 or 5) were further analyzed. Every malignant lesion was verified if it was identified by one of both or by both modalities. In 20 of 42 patients altogether 100 malignant lesions were present. In 11/20 patients in total 15 local recurrences (15 in MRI/ 9 in CT: 9 CT/MRI, 6 MRI only, 0 CT only; P = .04) were found with a statistically significant better performance of MRI. Regarding lymph node metastases, in total 13 lesions (12 in MRI/ 8 in CT: 7 CT/MRI, 5 MRI only, 1 CT only; P = .22) in 8/20 patients were found with no significant difference between both modalities. Furthermore, in 9/20 patients in total 72 lung lesions (40 in MRI/ 63 in CT: 31 CT/MRI, 9 MRI only, 32 CT only; P = .001) were found with a statistically significant better performance of CT. In 33/42 patients follow up was available and supported the observations. In patients with recurrent DTC, PET/MRI showed superiority compared to PET/CT in evaluation of the neck region. PET/MRI was inferior to PET/CT in evaluation of the lung. PET/MRI in combination with a low dose CT of the lung may thus represent the ideal staging tool in patients with recurrent DTC.

Mouse models are commonly used to study the biodistribution of novel radioligands, but alternative models corresponding to the 3Rs principles, such as the chorioallantoic membrane (CAM) model, are highly required. While there are promising data from the CAM model regarding target-specific radiolabeled compounds, its utility for assessing macromolecule biodistribution and analyzing the EPR effect remains to demonstrated. Using 89Zr-labeled human serum albumin, the accumulation of nontarget-specific macromolecules in CAM and mouse xenograft models was studied using PET and MRI. Therefore, the radioligand [89Zr]Zr-DFO-HSA was analyzed in both chicken embryos (n = 5) and SCID mice (n = 4), each with TZM-bl and PC-3 tumor entities. Dynamic PET and anatomical MRI, as well as ex vivo biodistribution analyses, were performed to assess ligand distribution over 24 h. Histological staining and autoradiography verified the intratumoral accumulation. The tumors were successfully visualized for CAM and mouse models by PET, and the albumin influx from the blood into the respective tumors did not differ significantly. The accumulation and retention of HSA in tumors due to the EPR effect was demonstrated for both models. These results highlight that the CAM model is a potential alternative to the mouse model for initial studies with novel radiolabeled macromolecules with respect to the 3Rs principles.