Targeted Therapy for Metastatic Prostate Cancer with Radionuclides

Progression to androgen-independent status is the main cause of death in patients with metastatic prostate cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly upregulated in prostate cancer. Therefore, it is an appropriate target for diagnosis and therapy of prostate cancer and its metastases. There is growing knowledge about promising response and low toxicity profile of radioligand therapy of metastatic castration-resistant prostate cancer using Lutetium-177-labeled PSMA ligands. For patients with only bone metastases, there are different radionuclides which have been used for decades. In this chapter, different methods of targeted radionuclide therapy of metastatic prostate cancer are described

Comparison of 18F-NaF Imaging, 99mTc-MDP Scintigraphy, and 18F-FDG for Detecting Bone Metastases

Bone is a common metastasis site in several malignancies, most importantly prostate and breast cancers. Given the significance of the early and accurate diagnosis of bone metastases for preliminary staging, treatment planning and monitoring, restaging, and survival prediction in patients with malignancy, it is critical to compare and contrast the strengths and weaknesses of imaging modalities. Although technetium-99m-labeled diphosphonates [99mTc-MDP] scintigraphy has been used for assessing skeletal involvement, there is a renewed interest in fluorine-18-labeled sodium fluoride [18F-NaF] bone imaging with positron emission tomography or positron emission tomography/computed tomography, since this approach provides essential advantages in bone metastases evaluation. This review study aimed to discuss the basic and technical aspects of 18F-NaF imaging and its mechanism of action, and compare this modality with the 99mTc-MDP bone scan and 18F-fluorodeoxyglucose using current evidence from the pertinent literature and case examples of the center in the study

Engagement 2.0. Vom passiven Wahrnehmen zum aktiven Nutzen neuer Kommunikationstechnologien

Im vorliegenden Beitrag beschreiben die Autoren einen seit zwei Jahren am Bundesinstitut für Erwachsenenbildung situierten Kurs, der engagierte Menschen in die Kommunikationstechniken und -werkzeuge im sogenannten Web 2.0 einführt. Als "politische Kommunikation" betrachten sie alle öffentlichkeitswirksamen bzw. zielgruppenbezogenen Aktivitäten für Anliegen, die im Selbstbewusstsein der AkteurInnen als öffentlich, als Interessen der Allgemeinheit oder aber auch als moralische Ansprüche an die Gesellschaft verstanden werden. Den Abschluss des Beitrages bildet der Ausblick auf eine im Entstehen befindliche Webcommunity der AbsolventInnen des Kurses. (DIPF/Orig.)The authors of the present article describe a course at the Austrian Federal Institute of Adult Education (bifeb) that has introduced dedicated people to Web 2.0 communication technologies and tools for the last two years. For the authors, “political communication” represents all public-oriented and target group related activities surrounding matters that are considered to be public in the self-awareness of those involved, interests of the general public or also moral demands on society. The end of the article provides a panorama of the web community that is being created by the course graduates. (DIPF/Orig.

Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition

Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3:a multicenter cohort study

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.acceptedVersio

Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: A mechanistic perspective for 18 F-FDG imaging of PSMA-suppressed tumors

Although the incidence of de novo neuroendocrine prostate cancer (PC) is rare, recent data suggest that low expression of prostatespecific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine hallmarks and androgen receptor (AR) suppression in PC. Previous clinical reports indicate that PCs with a phenotype similar to neuroendocrine tumors can be more amenable to imaging by 18F-FDG than by PSMA-targeting radioligands. In this study, we evaluated the association between neuroendocrine gene signature and 18F-FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported 18F-FDG avidity of PSMA suppressed tumors. Methods: Data-mining approaches, cell lines, and patient-derived xenograft models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes HK1-HK3 and GCK), and PSMA (FOLH1 gene) after AR inhibition and in correlation with neuroendocrine hallmarks. Also, we characterize a neuroendocrine-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no neuroendocrine histopathology. We measured glucose uptake in a neuroendocrine-induced in vitro model and a zebrafish model by nonradioactive imaging of glucose uptake using a fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrated that a neuroendocrine gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR inhibitors, high expression of GCK and low expression of SLC2A12 correlated with neuroendocrine histopathology and PSMA gene suppression. GLUT12 suppression and upregulation of glucokinase were observed in neuroendocrine- induced PC cell lines and patient-derived xenograft models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: A neuroendocrine gene signature in neuroendocrine PC and NELPC associates with a distinct transcriptional profile of GLUTs and hexokinases. PSMA suppression correlates with GLUT12 suppression and glucokinase upregulation. Alteration of 18F-FDG uptake-associated genes correlated positively with higher glucose uptake in AR- and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient preclinical method for monitoring nonradioactive glucose uptake