Nanobodies are small recombinant antigen-binding fragments derived from camelid heavy-chain only antibodies. Due to their compact structure, pharmacokinetics of nanobodies are favorable compared to full-size antibodies, allowing rapid accumulation to their targets after intravenous administration, while unbound molecules are quickly cleared from the circulation. In consequence, high signal-to-background ratios can be achieved, rendering radiolabeled nanobodies high-potential candidates for imaging applications in oncology, immunology and specific diseases, for instance in the cardiovascular system. In this review, a comprehensive overview of central aspects of nanobody functionalization and radiolabeling strategies is provided.

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20–50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.

Background: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients’ quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients’ QOL with few side effects. Study design: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Nanobodies sind die antigenbindenden Fragmente eines speziellen Antikörperformats, welches zum Beispiel in Kameliden vorkommt. Die Größe, Struktur und Beschaffenheit von Nanobodies bringen viele Vorteile mit sich, wodurch sie als exzellente Vehikel für die Entwicklung von Radiotracern in der nuklearmedizinischen Bildgebung und Therapie von großem Wert sind. Zu diesem Zweck werden die entsprechenden Radiohalogene oder Radiometalle auf unterschiedliche Art und Weise selektiv oder unselektiv an der Peptidkette des Nanobody’s angebracht. Die indirekte Radiohalogenierung mittels prosthetischer Gruppen und die Postmarkierung von bereits eingebrachten Chelatoren mit Radiometallen sind die bevorzugten Markierungsstrategien. Am häufigsten erfolgt die Tracerentwicklung über den His₆-Tag mit ^99mTc-Tricarbonyl. Präklinisch und auch zum Teil klinisch konnte die Eignung von verschiedenen nanobodybasierten Tracern bereits gezeigt werden. Nanobodies are the antigen-binding fragments of a special antibody format, which for example can be found in camelids. The size, structure and nature of nanobodies implies many advantages, by which they are of great value as excellent vehicles for the development of radiotracers in nuclear medical imaging and therapy. For this purpose, the appropriate radiohalogens or radiometals are attached in different ways selectively or unselectively to the peptide chain of the nanobody. The indirect radiohalogenation by means of prosthetic groups and the post-labeling of already introduced chelators with radiometals are the preferred labeling strategies. Most commonly, the tracer development takes place through the His₆-tag with ^99mTc-tricarbonyl. Preclinically and also in parts clinically, the suitability of different nanobody-based tracers could already be demonstrated. Article published online: 01 March 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany