Search Results (24)

The convergence of nanotechnology with nuclear medicine has led to the development of theranostic nanoplatforms that combine targeted imaging and therapy within a single system. This review provides a critical and updated synthesis of the current state of nanoplatform-based theranostics, with a particular focus on their application in oncology. We explore multifunctional nanocarriers that integrate diagnostic radionuclides for SPECT/PET imaging with therapeutic radioisotopes (α-, β-, or Auger emitters), chemotherapeutics, and biological targeting ligands. We highlight advances in nanomaterial engineering—such as hybrid architectures, surface functionalization, and stimuli-responsive designs—that improve tumor targeting, biodistribution, and therapeutic outcomes. Emphasis is placed on translational challenges including pharmacokinetics, toxicity, regulatory pathways, and GMP-compliant manufacturing. The article closes with a forward-looking perspective on how theranostic nanoplatforms could reshape the future of personalized oncology through precision-targeted diagnostics and radiotherapy. Full article

Nanoradiopharmaceuticals integrate nanotechnology with nuclear medicine to enhance the precision and effectiveness of radiopharmaceuticals used in diagnostic imaging and targeted therapies. Nanomaterials offer improved targeting capabilities and greater stability, helping to overcome several limitations. This review presents a comprehensive overview of the fundamental design principles, radiolabeling techniques, and biomedical applications of nanoradiopharmaceuticals, with a particular focus on their expanding role in precision oncology. It explores key areas, including single- and multi-modal imaging modalities (SPECT, PET), radionuclide therapies involving beta, alpha, and Auger emitters, and integrated theranostic systems. A diverse array of nanocarriers is examined, including liposomes, micelles, albumin nanoparticles, PLGA, dendrimers, and gold, iron oxide, and silica-based platforms, with an assessment of both preclinical and clinical research outcomes. Theranostic nanoplatforms, which integrate diagnostic and therapeutic functions within a single system, enable real-time monitoring and personalized dose optimization. Although some of these systems have progressed to clinical trials, several obstacles remain, including formulation stability, scalable manufacturing, regulatory compliance, and long-term safety considerations. In summary, nanoradiopharmaceuticals represent a promising frontier in personalized medicine, particularly in oncology. By combining diagnostic and therapeutic capabilities within a single nanosystem, they facilitate more individualized and adaptive treatment approaches. Continued innovation in formulation, radiochemistry, and regulatory harmonization will be crucial to their successful routine clinical use. Full article

Multidrug resistance (MDR) represents a major obstacle to successful chemotherapy and, due to overlapping defense mechanisms, such as enhanced DNA repair and the evasion of apoptosis, can also be associated with radioresistance. In this study, we investigated whether MDR breast cancer cells (MCF-7/CMF) exhibit reduced susceptibility to radiation-induced DNA fragmentation compared to their non-resistant parental counterpart (MCF-7). Using a nucleosome-based ELISA, we quantified the chromatin fragmentation in MCF-7 and MCF-7/CMF cells following their exposure to four radiopharmaceuticals: [^99mTc]pertechnetate, [¹³¹I]NaI (sodium iodide), [¹²⁵I]NaI, and the DNA-incorporating compound [¹²⁵I]iododeoxyuridine ([¹²⁵I]IdU). Each radioactive preparation was assessed across a range of activity concentrations, using a two-way ANOVA. For [^99mTc]pertechnetate and [¹³¹I]NaI, significantly higher DNA fragmentation was observed in the sensitive cell line, whereas [¹²⁵I]NaI showed no significant difference between the two phenotypes. In contrast to the other radiopharmaceuticals, [¹²⁵I]IdU induced greater fragmentation in resistant cells. This finding was supported by the statistical analysis (a 63.7% increase) and visualized in the corresponding dose–response plots. These results highlight the critical role of the intranuclear enrichment of Auger emitters and support further development of radiopharmaceuticals in accordance with this principle. Our data suggest that radiotoxicity is governed not by linear energy transfer (LET) alone, but, fundamentally, by the spatial proximity of the radionuclide to the DNA. Targeting tumor cell DNA with precision radiotherapeutics may, therefore, offer a rational strategy to overcome MDR in breast cancer. Full article

The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (^58mCo) and the Positron Emission Tomography-isotope cobalt-55 (⁵⁵Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co²⁺ and Co³⁺. With cobalt-57 (⁵⁷Co) serving as a surrogate radionuclide for ^55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [⁵⁷Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of ⁵⁷Co from the complex. In conclusion, [⁵⁷Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR. Full article

Targeted Auger emitters are being considered as a cancer treatment owing to the high linear energy transfer of Auger electrons. When targeted to cancers, this allows for a highly efficient treatment with a low risk of damage to surrounding healthy tissue. The purpose of this study was to determine the most DNA-damaging Auger emitters from a range of radionuclides, some of which are clinically utilised. A Monte Carlo method-based software (Geant4-DNA version 10.7) was used to determine the energy deposition and number of DNA double-strand breaks from Auger (and internal conversion) electrons imposed on a tetranucleosome. The Auger emitters, ¹¹⁹Sb and ¹⁰³Pd, have similar or slightly greater damaging properties compared to ¹²³I, ¹¹¹In, and ⁸⁹Zr. ^193mPt demonstrated the greatest therapeutic potency. Whilst ¹²⁵I was highly damaging, its relatively long half-life (60 days) makes it less desirable for clinical use. Geant4-DNA modelling identified the radionuclide ^193mPt as being highly favourable for use in radiotherapy. Full article

Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose–response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125. We compared the energy deposition and single strand break (SSB) yield at each base pair location in a short B-form DNA (B-DNA) geometry with existing simulation and experimental data, considering both physical direct and chemical indirect hits. Additionally, we evaluated dosimetric differences between our high-resolution B-DNA target and a previously published simple B-DNA geometry. Overall, our benchmarking results for SSB yield from I-125 decay exhibited good agreement with both simulation and experimental data. Using this simulation, we then evaluated the SSB and double strand break (DSB) yields caused by a theranostic Br-77-labeled poly ADP ribose polymerase (PARP) inhibitor radiopharmaceutical. The results indicated a predominant contribution of chemical indirect hits over physical direct hits in generating SSB and DSB. This study lays the foundation for future investigations into the nano-dosimetric properties of RPT. Full article

Prostate cancer (PCa) is one of the most prevalent cancer diagnoses among men in the United States and in several other developed countries. The prostate specific membrane antigen (PSMA) has been recognized as a promising molecular target in PCa, which has led to the development of specific radionuclide-based tracers for imaging and radiopharmaceuticals for PSMA targeted therapy. These compounds range from small molecule ligands to monoclonal antibodies (mAbs). Monoclonal antibodies play a crucial role in targeting cancer cell-specific antigens with a high degree of specificity while minimizing side effects to normal cells. The same mAb can often be labeled in different ways, such as with radionuclides suitable for imaging with Positron Emission Tomography (β+ positrons), Gamma Camera Scintigraphy (γ photons), or radiotherapy (β− electrons, α-emitters, or Auger electrons). Accordingly, the use of radionuclide-based PSMA-targeting compounds in molecular imaging and therapeutic applications has significantly grown in recent years. In this article, we will highlight the latest developments and prospects of radiolabeled mAbs that target PSMA for the detection and treatment of prostate cancer. Full article

The present review aims to explore the potential targets/partners for future targeted radionuclide therapy (TRT) strategies, wherein cancer cells often are not killed effectively, despite receiving a high average tumor radiation dose. Here, we shall discuss the key factors in the cancer genome, especially those related to DNA damage response/repair and maintenance systems for escaping cell death in cancer cells. To overcome the current limitations of TRT effectiveness due to radiation/drug-tolerant cells and tumor heterogeneity, and to make TRT more effective, we propose that a promising strategy would be to target the DNA maintenance factors that are crucial for cancer survival. Considering their cancer-specific DNA damage response/repair ability and dysregulated transcription/epigenetic system, key factors such as PARP, ATM/ATR, amplified/overexpressed transcription factors, and DNA methyltransferases have the potential to be molecular targets for Auger electron therapy; moreover, their inhibition by non-radioactive molecules could be a partnering component for enhancing the therapeutic response of TRT. Full article

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m (^99mTc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. ^99mTc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of ^99mTc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of ^99mTc used in clinical settings. Data are presented on AuNRs’ chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after ^99mTc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug–AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented. Full article

There is an unmet need for better therapeutic strategies for advanced prostate cancer. Poly (ADP-ribose) polymerase-1 (PARP-1) is a chromatin-binding DNA repair enzyme overexpressed in prostate cancer. This study evaluates whether PARP-1, on account of its proximity to the cell’s DNA, would be a good target for delivering high-linear energy transfer Auger radiation to induce lethal DNA damage in prostate cancer cells. We analyzed the correlation between PARP-1 expression and Gleason score in a prostate cancer tissue microarray. A radio-brominated Auger emitting inhibitor ([⁷⁷Br]Br-WC-DZ) targeting PARP-1 was synthesized. The ability of [⁷⁷Br]Br-WC-DZ to induce cytotoxicity and DNA damage was assessed in vitro. The antitumor efficacy of [⁷⁷Br]Br-WC-DZ was investigated in prostate cancer xenograft models. PARP-1 expression was found to be positively correlated with the Gleason score, thus making it an attractive target for Auger therapy in advanced diseases. The Auger emitter, [⁷⁷Br]Br-WC-DZ, induced DNA damage, G2-M cell cycle phase arrest, and cytotoxicity in PC-3 and IGR-CaP1 prostate cancer cells. A single dose of [⁷⁷Br]Br-WC-DZ inhibited the growth of prostate cancer xenografts and improved the survival of tumor-bearing mice. Our studies establish the fact that PARP-1 targeting Auger emitters could have therapeutic implications in advanced prostate cancer and provides a strong rationale for future clinical investigation. Full article

Although ^99mTc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available “model” radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates ^99mTc-TPP-BBN and ^99mTc-AO-BBN (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. ^99mTc-TPP-BBN and ^99mTc-AO-BBN caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener ^99mTc-BBN, leading to an augmented formation of γH2AX foci and micronuclei. ^99mTc-TPP-BBN also caused a reduction of the mtDNA copy number, although it enhanced the ATP production by PC3 cells. These differences can be attributed to the augmented uptake of ^99mTc-TPP-BBN in the mitochondria and enhanced uptake of ^99mTc-AO-BBN in the nucleus, allowing the irradiation of these radiosensitive organelles with the short path-length AEs emitted by ^99mTc. In particular, the results obtained for ^99mTc-TPP-BBN reinforce the relevance of targeting the mitochondria to promote stronger radiobiological effects by AE-emitting radioconjugates. Full article

Cancer stem cells (CSCs) are resistant to conventional therapy and present a major clinical challenge since they are responsible for the relapse of many cancers, including non-small cell lung cancer (NSCLC). Hence, future successful therapy should also eradicate CSCs. Auger electrons have demonstrated promising therapeutic potential and can induce DNA damage while sparing surrounding cells. Here, we sort primary patient-derived NSCLC cells based on their expression of the CSC-marker CD44 and investigate the effects of cisplatin and a thymidine analog (deoxyuridine) labeled with an Auger electron emitter (¹²⁵I). We show that the CD44⁺ populations are more resistant to cisplatin than the CD44⁻ populations. Interestingly, incubation with the thymidine analog 5-[¹²⁵I]iodo-2′-deoxyuridine ([¹²⁵I]I-UdR) induces equal DNA damage, G2/M cell cycle arrest, and apoptosis in the CD44⁻ and CD44⁺ populations. Our results suggest that Auger electron emitters can also eradicate resistant lung cancer CD44⁺ populations. Full article

Somatostatin receptors (SSTs) are recognized as favorable molecular targets in neuroendocrine tumors (NETs) and neuroendocrine neoplasms (NENs), with subtype 2 (SST₂) being the predominantly and most frequently expressed. PET/CT imaging with ⁶⁸Ga-labeled SST agonists, e.g., ⁶⁸Ga-DOTA-TOC (SomaKit TOC^®) or ⁶⁸Ga-DOTA-TATE (NETSPOT^®), plays an important role in staging and restaging these tumors and can identify patients who qualify and would potentially benefit from peptide receptor radionuclide therapy (PRRT) with the therapeutic counterparts ¹⁷⁷Lu-DOTA-TOC or ¹⁷⁷Lu-DOTA-TATE (Lutathera^®). This is an important feature of SST targeting, as it allows a personalized treatment approach (theranostic approach). Today, new developments hold promise for enhancing diagnostic accuracy and therapeutic efficacy. Among them, the use of SST₂ antagonists, such as JR11 and LM3, has shown certain advantages in improving image sensitivity and tumor radiation dose, and there is evidence that they may find application in other oncological indications beyond NETs and NENs. In addition, PRRT performed with more cytotoxic α-emitters, such as ²²⁵Ac, or β^- and Auger electrons, such as ¹⁶¹Tb, presents higher efficacy. It remains to be seen if any of these new developments will overpower the established radiolabeled SST analogs and PRRT with β^--emitters. Full article

Photoluminescence in a double heterostructure based on a ternary InAsSb solid solution was observed in the mid-infrared range of 2.5–4 μm. A range of compositions of the InAs_1−ySb_y ternary solid solution has been established, where the energy resonance between the band gap and the splitting-off band in the valence band of the semiconductor can be achieved. Due to the impact of nonradiative Auger recombination processes, different temperature dependence of photoluminescence intensity was found for the barrier layer and the narrow-gap active region, respectively. It was shown that efficient high-temperature photoluminescence can be achieved by suppressing the nonradiative Auger recombination (CHHS) process. Increased temperature, for which the energy gap is lower than the split-off band energy, leads to violation of the resonance condition in narrow gap antimonide compounds, which explains the observed phenomenon. This finding might influence future application of the investigated material systems in mid-infrared emitters used for, e.g., optical gas sensing. Full article