CXCR4 is a chemokine receptor that is overexpressed in various human cancers and is involved in tumor metastasis. The aim of this proof-of-concept study was to evaluate a novel CXCR4-targeted PET probe in patients with solid cancers with reported in vitro evidence of CXCR4 overexpression and to estimate its potential diagnostic value. Methods: Twenty-one patients with histologically proven pancreatic cancer, laryngeal cancer, non-small cell lung cancer, prostate cancer, melanoma, breast cancer, hepatocellular carcinoma, glioblastoma, sarcoma, or cancer of unknown primary underwent PET imaging using the novel CXCR4 nuclear probe 68 Ga-pentixafor. The SUV max of the liver, spleen, and bone marrow was measured to determine physiologic tracer distribution. For evaluation of tracer accumulation in solid cancers, SUV max and tumor-tobackground (T/B) ratios were determined in a total of 43 malignant lesions, including 8 primary tumors, 3 locally recurrent tumors, and 32 metastases. When available, the SUV max of malignant lesions was compared with the corresponding SUV max measured in routine 18 F-FDG PET. Results: Moderate tracer accumulation was detectable in the liver, bone marrow, and spleen, with a mean SUV max of 3.1, 3.7, and 5.6, respectively. By visual interpretation criteria, 9 of 11 primary and locally recurrent tumors were detectable, exhibiting a mean SUV max of 4.7 (range, 2.1-10.9) and a mean T/B ratio of 2.9. Twenty of 32 evaluated metastases were visually detectable (mean SUV max , 4.5 [range, 3.2-13.8]; mean T/B ratio, 2.8). The highest signal was detected in a patient with non-small cell lung cancer (SUV max , 10.9; T/B ratio, 8.4) and a patient with cancer of unknown primary (SUV max , 13.8; T/B ratio, 8.1). Compared with 18 F-FDG PET, which was additionally performed in 10 patients, 68 Gapentixafor PET had a lower SUV max in all measured malignant lesions. Conclusion: On the basis of these first observations in a small and heterogeneous patient cohort, the in vitro CXCR4 expression profile of solid cancers and metastases described in the previous literature does not seem to sufficiently depict the in vivo distribution revealed by CXCR4-targeted PET. Moreover, the detectability of solid cancers seems to be generally lower for 68 Ga-pentixafor than for 18 F-FDG PET.

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StatementDie Behandlungsstrategien basieren auf der exakten Diagnose, den Vorbehandlungen und auf dem Erkrankungsstadium.Konsensus: 100 % EmpfehlungenDie Therapie der MF soll entsprechend den in Tabelle 1 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie des Sézary-Syndroms soll entsprechend den in Tabelle 2 gelisteten Empfehlungen erfolgen. Konsensus: 86 % Die Therapie der CD30+ lymphoproliferativen Erkrankungen der Haut soll entsprechend den in Tabelle 3 gelisteten Empfehlungen erfolgen. Konsensus: 100 % Die Therapie der kutanen B Zell-Lymphome soll entsprechend den Tabellen 4a und 4b gelisteten Empfehlungen erfolgen. Konsensus: 100 %

Objective: The aim of this study was to clarify the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) pathways in thyroid tumourigenesis. Methods: We examined VEGF, VEGFR-1 and VEGFR-2 expression on 34 papillary thyroid carcinomas (PTCs), 18 follicular thyroid carcinomas (FTCs), eight poorly differentiated thyroid carcinomas (PDTCs) and on a thyroid tumour-derived cell line (NPA 0 87) by immunohistochemistry, reverse transcriptase PCR, immunofluorescence and Western blotting. Results: We have demonstrated that VEGF expression was significantly (P , 0.05) more prevalent in PTCs (79%) than in FTCs (50%) or PDTCs (37%). Similarly, 76% of PTCs, 83% of FTCs and 25% of PDTCs expressed VEGFR-1, whereas 68% of PTCs, 56% of FTCs and 37% of PDTCs expressed VEGFR-2. Coexpression of VEGF and its receptors was observed in 50% of PTCs, 39% of FTCs and 12% of PDTCs, raising the possibility that VEGF may signal in an autocrine loop in these neoplasias, as observed previously for other types of cancer. In agreement with the idea that autocrine VEGF signalling plays an important role in thyroid carcinogenesis, the blockade of either VEGF or its receptors with neutralizing antibodies significantly reduced cell viability and increased apoptosis levels of the VEGFR-positive thyroid tumour cell line NPA 0 87. Conclusions: Our results highlight a previously undefined VEGF autocrine action in thyroid carcinomas which could play a crucial role in tumour cell survival and could represent a useful therapeutic target for thyroid tumours.European Journal of Endocrinology 153 701-709

The objective of this investigation was to determine the diagnostic value of unilateral edema in differentiating benign from malignant breast disease on T2w-TSE images in MR-Mammography (MRM). All patients from a 10-year period undergoing surgery in the same institution after having received MRM in our department were included in this prospective analysis of previous acquired examinations. To eliminate bias caused by prior procedures, all patients having had biopsy, operation, radiation therapy, or chemotherapy before MRM were excluded. T2w-TSE images were acquired after a dynamic contrast-enhanced series of T1-weighted images in a standardized examination protocol (1.5 T). Edema was defined as a high-signal intensity on T2w-TSE images and it was categorized as absent, perifocal, or diffuse. Examinations were rated by two experienced observers blinded to all procedures and results following MRM. In cases of disconcordance, the opinion of a third radiologist decided. Statistical testing included Pearson's Chi-squared test and Fisher's exact testing. A total of 1,010 patients with a mean age of 55 years (SD: 11.6 years, range: 16-87 years) with 1,129 histologically verified lesions were included in this investigation. After removing all patients with prior procedures from the patient collective, 974 lesions were left for statistical analysis. Perifocal edema was highly significantly (p < 0.001) associated with malignant disease, leading to a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33.5%, 93.9%, 89.6, and 57.1%, respectively. Unilateral edema in general showed the following diagnostic parameters: sensitivity 53.0%, specificity 80.5%, PPV 80.9%, and NPV 52.3%. Edema seems to be associated with malignancy in the majority of cases. Especially, specificity and PPV were found to be high. These findings may be helpful in diagnostic decisions on otherwise equivocal cases.

A cute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [ 68 Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche.

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ObjectiveThe adjacent vessel sign (AVS) is a descriptor for differentiating malignant from benign breast lesions on breast MRI (bMRI). This investigation was designed to verify the previous reports on the diagnostic accuracy of AVS and to assess correlation between AVS, histopathological diagnosis, lesion size and lesion grade.Materials and MethodsThis study was approved by the local ethical committee. Experienced radiologists evaluated 1,084 lesions. The exclusion criteria were no histological verification after bMRI and breast interventions that were done up to one year before bMRI (surgery, core biopsy, chemo- or radiation therapy). The native and dynamic contrast-enhanced T1-weighted series were acquired using standardized protocols. The AVS was rated positive if a vessel leading to a lesion could be visualized. Prevalence of an AVS was correlated with the lesions' size, grade and histology using Chi-square-tests.ResultsThe AVS was significantly associated with malignancy (p < 0.001; sensitivity: 47%, specificity: 88%, positive-predictive-value [PPV]: 85%). Malignant lesions > 2 cm more often presented with an AVS than did those malignant lesions < 2 cm (p < 0.0001; sensitivity: 65%, PPV: 90%). There was no correlation of the AVS with the tumor grade. The prevalence of an AVS didn't significantly differ between invasive lobular carcinomas versus ductal carcinomas. In situ cancers were less frequently associated with an AVS (p < 0.001).ConclusionThe adjacent vessel sign was significantly associated with malignancy. Thus, it can be used to accurately assess breast lesions on bMRI. In this study, the AVS was particularly associated with advanced and invasive carcinomas.