It has been proven and confirmed in numerous repeated tests, that the use of a combination of several therapeutic methods gives much better treatment results than in the case of separate therapies. Particularly promising is the combination of ionizing radiation and magnetic hyperthermia in one drug. To achieve this objective, magnetite nanoparticles have been modified in their core with α emitter ²²⁵Ac, in an amount affecting only slightly their magnetic properties. By 3-phosphonopropionic acid (CEPA) linker nanoparticles were conjugated covalently with trastuzumab (Herceptin^®), a monoclonal antibody that recognizes ovarian and breast cancer cells overexpressing the HER2 receptors. The synthesized bioconjugates were characterized by transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) measurement, thermogravimetric analysis (TGA) and application of ¹³¹I-labeled trastuzumab for quantification of the bound biomolecule. The obtained results show that one ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab bioconjugate contains an average of 8–11 molecules of trastuzumab. The labeled nanoparticles almost quantitatively retain ²²⁵Ac (>98%) in phosphate-buffered saline (PBS) and physiological salt, and more than 90% of ²²¹Fr and ²¹³Bi over 10 days. In human serum after 10 days, the fraction of ²²⁵Ac released from ²²⁵Ac@Fe₃O₄ was still less than 2%, but the retention of ²²¹Fr and ²¹³Bi decreased to 70%. The synthesized ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab bioconjugates have shown a high cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptor in-vitro. The in-vivo studies indicate that this bioconjugate exhibits properties suitable for the treatment of cancer cells by intratumoral or post-resection injection. The intravenous injection of the ²²⁵Ac@Fe₃O₄-CEPA-trastuzumab radiobioconjugate is excluded due to its high accumulation in the liver, lungs and spleen. Additionally, the high value of a specific absorption rate (SAR) allows its use in a new very perspective combination of α radionuclide therapy with magnetic hyperthermia.

Actinium-225 (²²⁵Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with ²²⁵Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with ²²⁵Ac at pH 5.6 (30 min at 70 °C), and in vitro stability was evaluated. In vitro cytotoxicity was assessed in U-87 MG cancer cells, and in vivo biodistribution was performed by intravenous and intratumoral administration of [²²⁵Ac]²²⁵Ac-Au@TADOTAGA in U-87 MG tumor-bearing mice. A preliminary study to assess therapeutic efficacy of the intratumorally-injected radio-nanomedicine was performed over a period of 22 days, while the necrotic effect on tumors was evaluated by a histopathology study. We have shown that [²²⁵Ac]²²⁵Ac-Au@TADOTAGA resulted in the retardation of tumor growth after its intratumoral injection in U87MG tumor-bearing mice, even though very low activities were injected per mouse. This gold nanoparticle radiopharmaceutical could be applied as an unconventional brachytherapy in injectable form for local radiation treatment of cancer.

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

Dual-modality contrast agents, such as radiolabeled nanoparticles, are promising candidates for a number of diagnostic applications, since they combine the advantages of two different imaging modalities, namely SPECT or PET imaging with MR imaging. The benefit of such a combination is to more accurately interpret disease and abnormalities in vivo, by exploiting the advantages of each imaging technique, i.e. high sensitivity for SPECT/PET, high resolution anatomical information for MRI. In this review article, we provide an overview of recent findings in the synthesis, evaluation and application of radiolabeled iron oxide nanoparticles as dual-modality SPECT/MRI and PET/MRI imaging probes.

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.

During the last decades, the utilization of imaging modalities such as single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) in every day clinical practice has enabled clinicians to diagnose diseases accurately at early stages. Radiolabeled iron oxide nanoparticles (RIONs) combine their intrinsic magnetic behavior with the extrinsic character of the radionuclide additive, so that they constitute a platform of multifaceted physical properties. Thus, at a practical level, RIONs serve as the physical parent of the so-called dual-modality contrast agents (DMCAs) utilized in SPECT/MRI and PET/MRI applications due to their ability to combine, at real time, the high sensitivity of SPECT or PET together with the high spatial resolution of MRI. This review focuses on the synthesis and in vivo investigation of both biodistribution and imaging efficacy of RIONs as potential SPECT/MRI or PET/MRI DMCAs.