The epidermal growth factor receptor (EGFR) has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a) chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b) with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

Currently, targeted alpha therapy is one of the most investigated topics in radiopharmaceutical cancer management. Especially, the alpha emitter ²²⁵Ac has excellent nuclear properties and is gaining increasing popularity for the treatment of various tumor entities. We herein report on the synthesis of two universal ²²⁵Ac-chelators for mild condition radiolabeling and binding to conjugate molecules of pharmacological interest via the copper-mediated click chemistry. A convenient radiolabeling procedure was investigated as well as the complex stability proved for both chelators and two PSMA (prostate-specific membrane antigen)-targeting model radioconjugates. Studies regarding affinity and cell survival were performed on LNCaP cells followed by biodistribution studies, which were performed using LNCaP tumor-bearing mice. High efficiency radiolabeling for all conjugates was demonstrated. Cell binding studies revealed a fourfold lower cell affinity for the PSMA radioconjugate with one targeting motif compared to the radioconjugate owing two targeting motifs. Additionally, these differences were verified by in vitro cell survival evaluation and biodistribution studies, both showing a higher cell killing efficiency for the same dose, a higher tumor uptake (15%ID/g) and a rapid whole body clearance after 24 h. The synthesized chelators will overcome obstacles of lacking stability and worse labeling needs regarding ²²⁵Ac complexation using the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid) chelator. Moreover, the universal functionalization expands the coverage of these chelators in combination with any sensitive bio(macro)molecule, thus improving treatment of any addressable tumor target.

Barium-131 is a single photon emission computed tomography (SPECT)-compatible radionuclide for nuclear medicine and a promising diagnostic match for radium-223/-224. Herein, we report on the sufficient production route ¹³³Cs(p,3n)¹³¹Ba by using 27.5 MeV proton beams. An average of 190 MBq barium-131 per irradiation was obtained. The SR Resin-based purification process led to barium-131 in high radiochemical purity. An isotopic impurity of 0.01% barium-133 was detectable. For the first time, radiolabeling of the ligand macropa with barium-131 was performed. Radiolabeling methods under mild conditions and reaction controls based on TLC systems were successfully applied. Small animal SPECT/ computed tomography (CT) measurements and biodistribution studies were performed using [¹³¹Ba]Ba(NO₃)₂ as reference and ¹³¹Ba-labeled macropa in healthy mice for the first time. Biodistribution studies revealed the expected rapid bone uptake of [¹³¹Ba]Ba²⁺, whereas ¹³¹Ba-labeled macropa showed a fast clearance from the blood, thereby showing a significantly (p < 0.001) lower accumulation in the bone. We conclude that barium-131 is a promising SPECT radionuclide and delivers appropriate imaging qualities in small animals. Furthermore, the relative stability of the ¹³¹Ba-labeled macropa complex in vivo forms the basis for the development of sufficient new chelators, especially for radium isotopes. Thereby, barium-131 will attain its goal as a diagnostic match to the alpha emitters radium-223 and radium-224.

Despite their attractive properties, internal targeted alpha therapies using ^223/224Ra are limited to bone-seeking applications. As there is no suitable chelator available, the search for new carriers to stably bind Ra²⁺ and to connect it to biological target molecules is necessary. Polyoxopalladates represent a class of compounds where Ra²⁺ can be easily introduced into the Pd-POM core during a facile one-pot preparation. Due to the formation of a protein corona, the connection to other targeting (bio)macromolecules is possible.

A new Center for Radiopharmaceutical Cancer Research was established at the Helmholtz-Zentrum Dresden-Rossendorf in order to centralize radionuclide production, radiopharmaceutical production and the chemical and biochemical research facilities. The newly installed cyclotron is equipped with two beamlines, two target selectors and several liquid, gas and solid target systems. The cyclotron including the target systems and first results of beam characterization measurements as well as results of the radionuclide production are presented. The produced radionuclides are automatically distributed from the targets to the destination hot cells. This process is supervised and controlled by an in-house developed system.

Despite its attractive properties, internal targeted alpha particle therapy using ^223/224Ra is currently limited to palliative bone-seeking applications. To make both radioisotopes accessible for the treatment of other cancer diseases, functionalized nanoparticles (NPs) based on BaSO₄ are proposed as carriers to stably bind radium to a targeting molecule. Although significant advances in the tailoring of BaSO₄-based NPs have been achieved, their preparation is strongly dependent on the use of surfactants and additives. Herein, the direct facile one-pot preparation of radium-doped, alendronate-functionalized BaSO₄ NPs from [²²⁴Ra]Ra(NO₃)₂, (NH₄)₂SO₄, BaCl₂ and alendronate in an aqueous medium has been reported. Remarkably, the size of the formed BaSO₄ NPs is independent of the anion used, but is controlled by the addition of organic solvents. Upon the addition of alendronate, amine functionalities were introduced on the NP surface. To evidence this modification, a fluorescent dye-containing alendronate was used. Additionally, a similar fluorescent NBD active ester was applied to prove the reactivity of the outer alendronate amine groups for a later connection of targeting molecules to follow the radiotherapeutic approach. The variations in the functionalities were examined by IR, and the morphology of the resulting BaSO₄ NPs was investigated in detail. DLS and TEM measurements showed that the average diameter of the nanoparticles was approx. 140 nm.