( 177 Lu-AMBA) is a radiolabeled bombesin derivative that is bound and internalized by cells expressing the G-proteincoupled gastrin-releasing peptide receptor (GRP-R) and is currently in phase I clinical trials. In previous radiotherapy studies with PC-3 xenografted mice, 177 Lu-AMBA treatment significantly increased survival and reduced tumor growth rates. The PC-3 tumor cell line has an elevated expression of GRP-Rs (2.5 · 10 5 /cell), whereas LNCaP-a prostate cancer metastatic cell line representing the early androgen-sensitive stage of prostate cancer-and DU145-an androgen-insensitive metastatic lineexpress lower receptor numbers (5.9 · 10 3 and 1.2 · 10 4 /cell, respectively). Because of tumor heterogeneity, the high number of receptors in the PC-3 line may not represent the clinical situation, and little definitive work on the GRP-R status of primary prostate tumors and metastases exists. We sought to evaluate the tumor binding and imaging potential of 177 Lu-AMBA in low GRP-R models of prostate cancer and determine how reduced expression affects 177 Lu-AMBA radiotherapy efficacy. Methods: The LNCaP and DU145 cell lines were used to determine the binding (K d ), retention, and efflux of 177 Lu-AMBA. Biodistribution radiotherapy, imaging, and autoradiography studies were performed in LNCaP, DU145, or PC-3 tumor-bearing male nude mice. Immunohistochemistry was used to determine the proliferative state in LNCaP and DU145 models and the vascular phenotype of LNCaP radiotherapy tumors. Results: 177 Lu-AMBA binds to GRP-R in these cell lines with high affinity (K d of LNCaP, 0.65 6 0.2 nM; K d of DU145, 0.53 6 0.1 nM). The uptake of 177 Lu-AMBA is at least 10-fold less in LNCaP and DU145 cell lines than it is in the PC-3 cell line. Autoradiography identifies activity concentrated in areas of viable tumor tissue, and g-images of 177 Lu-AMBA identify tumors in vivo. Despite having lower uptake, 177 Lu-AMBA demonstrated radiotherapeutic efficacy and decreased proliferation in the LNCaP and DU145 xenografts; in the LNCaP model, 177 Lu-AMBA normalized the phenotype of microvasculature, reducing tumoral blood pooling. Conclusion: 177 Lu-AMBA is a single radiolabeled agent that combines targeted radiotherapy after imaging dosimetry with the potential for single-agent or multimodality therapy for prostate cancer. Prost ate cancer is the leading cause of cancer death in men, with an estimated 186,320 cases diagnosed and more than 28,000 deaths in the United States during 2008 (1).The design of a therapeutic course for the patient with prostate cancer can be particularly difficult because of the heterogeneity of the disease. The phenotypic characteristics of metastatic prostate cancer can show a broad spectrum, even within the same patient at the same time (2). The development of a single radiolabeled agent that could function as both a radiotherapeutic and an imaging agent for dosimetry, with the potential as an adjunct to traditional chemotherapy, could ameliorate these difficulties and result in better management of ...

Tween-20 and injected intravenously into patients with advanced NSCLC. Following intravenous injection of 131 I-labeled NM404 ( < 1 mCi), patients with advanced NSCLC were scanned at 3, 6, 24, 48 and 96 h and at 11 days on a GE Maxxus dual-head SPECT imaging system. Blood and urine samples were collected and analyzed at various times over 7 days and again at 30 days (blood only) after injection of NM404. Results: Initial qualitative imaging results from seven patients indicate that 131 I-labeled NM404 clearly localizes in pulmonary masses as early as 6 h after injection and is selectively retained in these tumors in excess of 11 days. Quantitative results, including dosimetry determination, are in progress. From a tolerability perspective, no symptoms or changes in vital signs or physical examination were observed after injection of radiolabeled NM404. Mild changes in blood counts, electrolytes and lipids which were observed were not clinically significant and all resolved within a matter of days. Conclusions: These preliminary findings suggest that NM404 is well tolerated and exhibits similar tumor uptake and retention properties in human NSCLC as seen previously in rodent tumor models. In order to evaluate its true promise as an imaging agent, however, we recently radiolabeled NM404 in >60% isolated yield with commercial iodine-124 (Eastern Isotopes), a new PET isotope with a 4-day half-life, and have recently acquired beautiful microPET images in several rodent tumor models as a prelude to upcoming human PET imaging studies in a variety of cancer types CMR 2005: 3.09 Preclinical efficacy of 177 Lu-AMBA, a radiotherapeutic targeting the GRP receptor Rationale and Objectives: We are developing 177 Lu-AMBA ( 177 Lu-DO3A-CH 2 CO-G-4-aminobenzoyl-QWAVGHLM-NH 2 ), a gastrinreleasing peptide receptor (GRP) agonist, for use as a radiotherapeutic. The preclinical studies reported here characterize its efficacy in mice including long-term, multidose therapeutic studies in a human prostate tumor xenograft model. This compound targets two of the receptors of the GRP-R family, which are upregulated in several human cancers. Methods: Biodistributions were performed in the PC-3 (human metastatic prostate carcinoma, bone) tumor-bearing male nude [Tac:Cr:(NCr)-Fox1 nu ] mouse model using 5 mCi of 177 Lu-AMBA, administered i.v., after 1 and 24 h. Radiotherapy studies with 177 Lu-AMBA were also conducted in the PC-3 model (starting tumor size 95 mm 3 ): administered 30 mCi/kg, s.c, single dose (n ¼ 32) or two equal doses administered at 0 and 14 days (n ¼ 36) or vehicle control s.c. (n ¼ 16). The mice were followed up to 120 days; necropsy was performed with tumors and organs collected for histology. Results: Renal excretion was predominant with only 4.4% ID/g kidney at 1 h and low retention. Tumor uptake was 6.4% ID/g at 1 h and 3.4% at 24 h. In long-term radiotherapeutic studies, treated mice dramatically outlived control mice. Two-dose mice showed increased tumor growth delay and improved overall survival compared with one-do...

In den letzten Jahren hat es auch auf der extremen Rechten einen Mobilisierungsschub gegeben. In dem Beitrag wird davon ausgegangen, dass eine Paramilitarisierung durch Milizen geschehen konnte, die mit »Weißen Nationalisten« gemeinsame Sache machen oder als Vollstrecker für Donald Trump und verbündete republikanische Politiker agieren würden. Tatsächlich scheinen alle rechtsextremen Gruppen am 6. Januar 2021 beim Angriff auf das Kapitol Trump als denjenigen gesehen zu haben, der zentrale Befehle geben würde. Das ist nicht geschehen. Aber die Beteiligung von so vielen »überzeugten Gläubigen« bei dieser Aktion macht die Frage nach der Paramilitarisierung noch dringlicher. Die Beteiligten könnten eine kritische Masse für künftige Bemühungen bieten, Pro-Trump-Paramilitärs jenseits der organisierten Gruppen entstehen zu lassen.

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