Review

Authors: Philip E Harris, Konstantin Zhernosekov

Lu-177 has been developed for the treatment of patients with peptide receptor radionuclide therapy (PRRT). A second generation pure no-carrier-added Lu-177 has a high specific activity and has waste disposal advantages over the first generation carrier-added Lu-177. PRRT has recently been developed for the treatment of neuroendocrine tumors (NETs). The majority of pancreatic and gastroenteric NETs (GEP-NETs) express the somatostatin receptors (SSTRs) 2 and 5. These receptors can be specifically targeted with a somatostatin peptide analogue (DOTATOC/DOTATATE) which can be chelated to a positron emission tomography (PET) emitting radioisotope such as Ga-68 for imaging or to a β-emitting radioisotope Lu-177 for therapy. A key advantage of this approach is that the receptor expression can be demonstrated by PET imaging before the patient is treated. Clinical studies in G1 and G2 GEP-NETS have demonstrated that PRRT is extremely effective in terms of progression free survival (PFS), symptom control and quality of life, with a well-established safety profile. A beneficial effect on outcome survival awaits to be confirmed. The first commercially available product Lu-177-DOTATATE was approved following the NETTER-1 trial in G1 and G2 GE-NETS. Lu-177-DOTATATE 7,4 GBq every 8 weeks for 4 cycles, together with octreotide LAR 30 mg monthly, demonstrated a median PFS of 28,4 months compared to 8,5 months for octreotide LAR 60 mg monthly. A second pivotal study COMPETE is currently in progress, comparing no carrier-added (n.c.a.) Lu-177-DOTATOC to the m-TOR inhibitor Everolimus in both GE-NETs and PNETs. Two studies, NETTER-2 and COMPOSE are currently underway in patients with high grade G2 and G3 NETs. Novel SSTR antagonists are being developed as next generation targeting molecules for SSTR2-expressing tumors. Antagonists have a higher tumor binding to receptors than agonists, opening up the potential indications for SSTR2 targeting to tumors which have a relatively lower expression of SSTR2 compared to NET such as small cell lung cancer, hepatocellular carcinoma and breast cancer. In addition to Lu-177, radioisotopes with different radiation properties such as Tb-161 and the α-emitter Ac-225 are being developed which have the potential to improve treatment efficacy across the range of G1 to G3 NETs.

Topics: Humans; Neuroendocrine Tumors; Octreotide; Gallium Radioisotopes; Actinium; Quality of Life; Radioisotopes; Radiopharmaceuticals

PubMed: 36387893
DOI: 10.3389/fendo.2022.941832

Review

Authors: Manish Ora, Neetu Soni, Aftab Hasan Nazar...

Metastatic malignancies have limited management strategies and variable treatment responses. Cancer cells develop beside and depend on the complex tumor microenvironment. Cancer-associated fibroblasts, with their complex interaction with tumor and immune cells, are involved in various steps of tumorigenesis, such as growth, invasion, metastasis, and treatment resistance. Prooncogenic cancer-associated fibroblasts emerged as attractive therapeutic targets. However, clinical trials have achieved suboptimal success. Fibroblast activation protein (FAP) inhibitor-based molecular imaging has shown encouraging results in cancer diagnosis, making them innovative targets for FAP inhibitor-based radionuclide therapies. This review summarizes the results of preclinical and clinical FAP-based radionuclide therapies. We will describe advances and FAP molecule modification in this novel therapy, as well as its dosimetry, safety profile, and efficacy. This summary may guide future research directions and optimize clinical decision-making in this emerging field.

Topics: Humans; Serine Endopeptidases; Membrane Proteins; Neoplasms; Cancer-Associated Fibroblasts; Radioisotopes; Positron Emission Tomography Computed Tomography; Fibroblasts; Gallium Radioisotopes; Tumor Microenvironment

PubMed: 37268422
DOI: 10.2967/jnumed.123.265594

Review

Authors: Filipa Mota, Alvaro A Ordonez, George Firth...

Bacterial infections remain a major threat to humanity and are a leading cause of death and disability. Antimicrobial resistance has been declared as one of the top ten threats to human health by the World Health Organization, and new technologies are urgently needed for the early diagnosis and monitoring of deep-seated and complicated infections in hospitalized patients. This review summarizes the radiotracers as applied to imaging of bacterial infections. We summarize the recent progress in the development of pathogen-specific imaging and the application of radiotracers in understanding drug pharmacokinetics as well as the local biology at the infection sites. We also highlight the opportunities for medicinal chemists in radiotracer development for bacterial infections, with an emphasis on target selection and radiosynthetic approaches. Imaging of infections is an emerging field. Beyond clinical applications, these technologies could provide unique insights into disease pathogenesis and expedite bench-to-bedside translation of new therapeutics.

Topics: Animals; Bacteria; Bacterial Infections; Drug Development; Humans; Molecular Imaging; Radioactive Tracers; Radioisotopes

PubMed: 32048838
DOI: 10.1021/acs.jmedchem.9b01623

Authors: Svend Borup Jensen

It is with great pleasure that I have accepted the challenge of reviewing and summarizing the articles published in Molecules through 2019 and 2020 on radioactive molecules [...].

Topics: Humans; Radioisotopes

PubMed: 33498459
DOI: 10.3390/molecules26030529

Review

Authors: Noami Daems, Carine Michiels, Stéphane Lucas...

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed as well as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies.

Topics: Metal Nanoparticles; Gold; Humans; Radioisotopes; Animals; Neoplasms

PubMed: 34237502
DOI: 10.1016/j.nucmedbio.2021.06.001

Review

Authors: Jasmine L Hatcher-Lamarre, Vanessa A Sanders, Mohammed Rahman...

Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic effects on tumor cells while mitigating dose to normal tissues. Two significant isotopes of interest within the area of TAT are thorium-227 and actinium-225 due to their nuclear characteristics. Both isotopes have physical half-lives suitable for coordination with larger biomolecules, and additionally actinium-225 has potential to serve as an in vivo generator. In this review, the authors will discuss the production, purification, labeling reactions, and biological studies of actinium-225 and thorium-227 complexes and clinical studies.

Topics: Animals; Humans; Actinium; Alpha Particles; Neoplasms; Radiochemistry; Radioisotopes; Thorium

PubMed: 33558017
DOI: 10.1016/j.nucmedbio.2020.08.004

Review

Authors: Pei-Sheng He, Feng Li, Guan-Hua Li...

BACKGROUND

The combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes (SLNs) in patients with breast cancer. However, some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs. We performed a systematic review to investigate the added value of blue dye in addition to radioisotope.

METHODS

We searched Pubmed and Embase. Prospective studies that compared the combination of radioisotope and blue dye with radioisotope alone were selected. The identification rate of SLNs and the false-negative rate were the main outcomes of interest. The odds ratios (ORs) and 95% confidential intervals (CIs) were calculated by using random-effects model.

RESULTS

Twenty-four studies were included. The combination of radioisotope and blue dye showed higher identification rate than radioisotope alone (OR = 2.03, 95% CI 1.53-2.69, P < 0.05). However, no statistically significant difference was revealed for patients after neoadjuvant chemotherapy (OR = 1.64, 95% CI 0.82-3.27, P > 0.05), or for studies with high proportion of patients with positive lymphoscintigraphy (OR = 1.41, 95% CI 0.83-2.39, P > 0.05). Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95% CI 0.44-1.29, P > 0.05).

CONCLUSIONS

Although the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection, the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy. Besides, the combined modality did not help lower the false-negative rate.

Topics: Breast Neoplasms; Coloring Agents; Female; Humans; Predictive Value of Tests; Prognosis; Radioisotopes; Sentinel Lymph Node Biopsy

PubMed: 26883751
DOI: 10.1186/s12885-016-2137-0

Review

Authors: Krzysztof Kilian, Krystyna Pyrzyńska

The concept of theranostics uses radioisotopes of the same or chemically similar elements to label biological ligands in a way that allows the use of diagnostic and therapeutic radiation for a combined diagnosis and treatment regimen. For scandium, radioisotopes -43 and -44 can be used as diagnostic markers, while radioisotope scandium-47 can be used in the same configuration for targeted therapy. This work presents the latest achievements in the production and processing of radioisotopes and briefly characterizes solutions aimed at increasing the availability of these radioisotopes for research and clinical practice.

Topics: Radiopharmaceuticals; Scandium; Radioisotopes; Precision Medicine

PubMed: 38005390
DOI: 10.3390/molecules28227668

Review

Authors: Janke Kleynhans, Adriano Duatti, Cristina Bolzati...

The β emitter, rhenium-188 (Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (Tc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases.

Topics: Radiopharmaceuticals; Technetium; Radioisotopes; Rhenium

PubMed: 36771153
DOI: 10.3390/molecules28031487

Review

Authors: Caroline Stokke, Monika Kvassheim, Johan Blakkisrud...

A search in PubMed revealed that 72 radionuclides have been considered for molecular or functional targeted radionuclide therapy. As radionuclide therapies increase in number and variations, it is important to understand the role of the radionuclide and the various characteristics that can render it either useful or useless. This review focuses on the physical characteristics of radionuclides that are relevant for radionuclide therapy, such as linear energy transfer, relative biological effectiveness, range, half-life, imaging properties, and radiation protection considerations. All these properties vary considerably between radionuclides and can be optimised for specific targets. Properties that are advantageous for some applications can sometimes be drawbacks for others; for instance, radionuclides that enable easy imaging can introduce more radiation protection concerns than others. Similarly, a long radiation range is beneficial in targets with heterogeneous uptake, but it also increases the radiation dose to tissues surrounding the target, and, hence, a shorter range is likely more beneficial with homogeneous uptake. While one cannot select a collection of characteristics as each radionuclide comes with an unchangeable set, all the 72 radionuclides investigated for therapy-and many more that have not yet been investigated-provide numerous sets to choose between.

Topics: Half-Life; Radioisotopes

PubMed: 36080198
DOI: 10.3390/molecules27175429