Concept Of Theranostics Research Articles

Navigating the landscape of theranostics in nuclear medicine: current practice and future prospects.

Theranostics refers to the combination of diagnostic biomarkers with therapeutic agents that share a specific target expressed by diseased cells and tissues. Nuclear medicine is an exciting component explored for itsapplicability in theranostic concepts in clinical and research investigations. Nuclear theranostics is based on the employment of radioactive compounds delivering ionizing radiation to diagnose and manage certain diseases employing binding with specifically expressed targets. In the realm of personalized medicine, nuclear theranostics stands as a beacon of potential, potentially revolutionizing disease management. Studies exploring the theranostic profile of radioactive compounds have been presented in this review along with a detailed explanation of radioactive compounds and their theranostic applicability in several diseases. It furnishes insights into their applicability across diverse diseases, elucidating the intricate interplay between these compounds and disease pathologies. Light is shed on the important milestones of nuclear theranostics beginning with radioiodine therapy in thyroid carcinomas, MIBG labelled with iodine in neuroblastoma, and several others. Our perspectives have been put forth regarding the most important theranostic agents along with emerging trends and prospects.

Global Governance for Personalized Medicine, Politics of Uncertainty, and Pierre Bourdieu.

How we choose to respond to uncertainty matters for robust and responsible science. New laws and consensus reports are popular instruments for global governance of emerging technology and attendant uncertainty. However, the sociologist Pierre Bourdieu noted that "[t]he judicial situation operates like a neutral space that neutralizes the stakes in any conflict through the de-realization and distancing implicit in the conversion of a direct struggle between parties into a dialogue between mediators." Put in other words, while law and legal modes of reasoning are certainly useful for conflict resolution and closure, their overprivileging in emerging technology and uncertainty governance can potentially bring about depoliticization by transforming the struggles and dissent necessary for democratic governance into a "dialogue between mediators." Hence, the critical sociological gaze offered by Bourdieu is particularly relevant for democratization of global governance of multiomics technologies and timely with the current uptake of personalized medicine. For example, in May 2023, the Romanian government introduced a law to give patients the right to personalized medicine. Personalized medicine is related to the larger umbrella concept and field of theranostics, the fusion of therapeutics and diagnostics. It is therefore timely to reflect on a "right for theranostics in planetary health," considering the potential for future pandemics and ecological crises in the 21st century. Rather than forcing consensus or convergence in an innovation ecosystem, dissent grounded in rigorous political theory, sociology of law and critical legal studies can strengthen democratization and global governance for personalized medicine and multiomics technologies.

Vascular targeted optical theranostics: enhanced photoplethysmography imaging of laser-induced singlet oxygen effects.

The work considers a theranostic system that implements a multimodal approach allowing the simultaneous generation of singlet oxygen and visualization of the various parameters of the vascular bed. The system, together with the developed data processing algorithm, has the ability to assess architectural changes in the vascular network and its blood supply, as well as to identify periodic signal changes associated with mechanisms of blood flow oscillation of various natures. The use of this system seems promising in studying the effect of laser-induced singlet oxygen on the state of the vascular bed, as well as within the framework of the theranostic concept of treatment and diagnosis of oncological diseases and non-oncological vascular anomalies.

Radiotheranostics in Oncology

This review discusses the urgent requirements in modern oncology to address the complexities associated with metastatic cancer, a condition that often lacks comprehensive understanding, particularly concerning receptor expression. The emerging concept of theranostics, which merges precise diagnostics and therapies within the precision medicine framework, underscores the need for further investigation. A central focus of this review is radiotheranostics, a versatile approach offering personalized diagnostic and therapeutic possibilities. It examines the intricate components of radiotheranostics, such as radionuclides, metal-complexing agents, and receptor-specific agents designed to target molecular markers linked to cancer selectively. The study explores potential applications of radiotheranostics, especially in scenarios where conventional treatments have limitations. Investigating patient acceptance and determining the optimal administration route are critical aspects that demand thorough examination to facilitate the integration of radiotheranostics into clinical practice. Furthermore, this review aims to reveal the potential of new ligands and isotopes to enhance the effectiveness of radiotheranostics. Molecular imaging, functioning at the molecular and cellular levels, constitutes a significant element of this study, delivering in-depth anatomical and functional insights. Recognizing the pivotal role of Cancer Stem Cells (CSCs) in precise cancer treatment, the review explores techniques for their identification and characterization within the framework of radiotheranostics. Despite its promise, radiotheranostics faces unique challenges from logistical constraints and regulatory intricacies, setting it apart from conventional chemotherapy. This review seeks to elucidate these challenges and provide potential solutions. In summary, this review responds to the crucial need for advancing our understanding and application of radiotheranostics, holding the potential to offer significant palliative measures, extend patient survival, and even provide cures, particularly for those with metastatic disease and suitable molecular targets.

Scandium Radioisotopes-Toward New Targets and Imaging Modalities.

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.

New developments for theranostic radioisotope production with solid targets at the Bern medical cyclotron

The concept of theranostics in nuclear medicine is based on the use of a pair of radioisotopes to label radiopharmaceuticals for both diagnosis and therapy and is essential for nuclear medicine developments. The production of novel medical radioisotopes using solid target stations is challenging and new instruments and methods are needed. A research program is ongoing at the 18 MeV Bern medical cyclotron, equipped with a Solid Target Station and a 6.5 m Beam Transfer Line ending in a separate bunker. To irradiate isotope-enriched materials in form of compressed powder pellets, a novel target coin was conceived and realized together with methods to assess the beam energy and the production cross sections. To optimize the irradiation procedure, a novel ultra-compact active irradiation system based on a specific magnetic lens and a two-dimensional beam detector was conceived, constructed and tested. The system allows to control on-line the size and position of the beam and to correct its characteristics by steering and focusing it in order to keep it on target. The first results on the production of several radionuclides (43Sc, 44Sc, 47Sc, 61Cu, 64Cu, 67Cu, 68Ga, 165Er, 165Tm, 167Tm and 155Tb) are presented.

Preclinical Evaluation of a 64Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma.

Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β+ and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [64Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [64Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [64Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM.

Theranostics in Hematooncology.

In the early 2000s, major clinical trials provided evidence of a favorable outcome from antibody-mediated radioimmunotherapy for hematologic neoplasms, which then led to Food and Drug Administration approval. For instance, the theranostic armamentarium for the referring hematooncologist now includes 90Y-ibritumomab tiuxetan for refractory low-grade follicular lymphoma or transformed B-cell non-Hodgkin lymphoma, as well as 131I-tositumomab for rituximab-refractory follicular lymphoma. Moreover, the first interim results of the SIERRA phase III trial reported beneficial effects from the use of 131I-anti-CD45 antibodies (Iomab-B) in refractory or relapsed acute myeloid leukemia. During the last decade, the concept of theranostics in hematooncology has been further expanded by C-X-C motif chemokine receptor 4-directed molecular imaging. Beyond improved detection rates of putative sites of disease, C-X-C motif chemokine receptor 4-directed PET/CT also selects candidates for radioligand therapy using β-emitting radioisotopes targeting the identical chemokine receptor on the lymphoma cell surface. Such image-piloted therapeutic strategies provided robust antilymphoma efficacy, along with desired eradication of the bone marrow niche, such as in patients with T- or B-cell lymphoma. As an integral part of the treatment plan, such radioligand therapy-mediated myeloablation also allows one to line up patients for stem cell transplantation, which leads to successful engraftment during the further treatment course. In this continuing education article, we provide an overview of the current advent of theranostics in hematooncology and highlight emerging clinical applications.

Utility of 68Ga-FAPI-04 PET/CT in Adenoid Cystic Carcinoma Compared With 18F-FDG PET/CT: Two Case Reports.

68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68Ga-FAPI-04 and 18F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68Ga-FAPI-04. In the second case, 68Ga-FAPI-04 outperformed 18F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts.

EANM enabling guide: how to improve the accessibility of clinical dosimetry

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

Advanced Radio Frequency Applicators for Thermal Magnetic Resonance Theranostics of Brain Tumors

Thermal Magnetic Resonance (ThermalMR) is a theranostic concept that combines diagnostic magnetic resonance imaging (MRI) with targeted thermal therapy in the hyperthermia (HT) range using a radiofrequency (RF) applicator in an integrated system. ThermalMR adds a therapeutic dimension to a diagnostic MRI device. Focused, targeted RF heating of deep-seated brain tumors, accurate non-invasive temperature monitoring and high-resolution MRI are specific requirements of ThermalMR that can be addressed with novel concepts in RF applicator design. This work examines hybrid RF applicator arrays combining loop and self-grounded bow-tie (SGBT) dipole antennas for ThermalMR of brain tumors, at magnetic field strengths of 7.0 T, 9.4 T and 10.5 T. These high-density RF arrays improve the feasible transmission channel count, and provide additional degrees of freedom for RF shimming not afforded by using dipole antennas only, for superior thermal therapy and MRI diagnostics. These improvements are especially relevant for ThermalMR theranostics of deep-seated brain tumors because of the small surface area of the head. ThermalMR RF applicators with the hybrid loop+SGBT dipole design outperformed applicators using dipole-only and loop-only designs, with superior MRI performance and targeted RF heating. Array variants with a horse-shoe configuration covering an arc (270°) around the head avoiding the eyes performed better than designs with 360° coverage, with a 1.3 °C higher temperature rise inside the tumor while sparing healthy tissue. Our EMF and temperature simulations performed on a virtual patient with a clinically realistic intracranial tumor provide a technical foundation for implementation of advanced RF applicators tailored for ThermalMR theranostics of brain tumors.

Optimized production of 67Cu based on cross section measurements of 67Cu and 64Cu using an 18 MeV medical cyclotron

RadioNuclide Therapy (RNT) in nuclear medicine is a cancer treatment based on the administration of radioactive substances that specifically target cancer cells in the patient. These radiopharmaceuticals consist of tumor-targeting vectors labeled with β−, α, or Auger electron-emitting radionuclides. In this framework, 67Cu is receiving increasing interest as it provides β−-particles accompanied by low-energy γ radiation. The latter allows to perform Single Photon Emission Tomography (SPECT) imaging for detecting the radiotracer distribution for an optimized treatment plan and follow-up. Furthermore, 67Cu could be used as therapeutic partner of the β+-emitters 61Cu and 64Cu, both currently under study for Positron Emission Tomography (PET) imaging, paving the way to the concept of theranostics. The major barrier to a wider use of 67Cu-based radiopharmaceutical is its lack of availability in quantities and qualities suitable for clinical applications. A possible but challenging solution is the proton irradiation of enriched 70Zn targets, using medical cyclotrons equipped with a solid target station. This route was investigated at the Bern medical cyclotron, where an 18 MeV cyclotron is in operation together with a solid target station and a 6-m-long beam transfer line. The cross section of the involved nuclear reactions were accurately measured to optimize the production yield and the radionuclidic purity. Several production tests were performed to confirm the obtained results.

Navigating thyroid cancer: a theranostics odyssey "joining the dots to make a line"

Over the past few decades, the incidence of thyroid cancer, which was once a relatively uncommon aspect of oncology, has significantly increased worldwide. This tendency makes opening of new horizons, and finding new modalities for both its diagnosis and therapy all the more crucial. The concept of theranostics in thyroid cancer has shown potential in individualizing treatments, tailoring therapies to the specific molecular characteristics of the patient\'s cancer.

EANM practice guideline for quantitative SPECT-CT

PurposeQuantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases.MethodsThese practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine.ConclusionThe present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.

Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, a paramount challenge for researchers and clinicians. GBMs exhibit the hallmark feature of aggressive invasion into the surrounding tissue. Among cell surface receptors involved in this process, members of the integrin family are known to be key actors of GBM invasion. Upregulation of integrins was reported in both tumor and stromal cells, making them a suitable target for innovative therapies targeting integrins in GBM patients, as their impairment disrupts tumor cell proliferation and invasive capacities. Among them, integrin-αvβ3 expression correlates with high-grade GBM. Driven by a plethora of preclinical biological studies, antagonists of αvβ3 rapidly became attractive therapeutic candidates to impair GBM tumorigenesis. In this perspective, the advent of nuclear medicine is currently one of the greatest components of the theranostic concept in both preclinical and clinical research fields. In this review, we provided an overview of αvβ3 expression in GBM to emphasize the therapeutic agents developed. Advanced current and future developments in the theranostic field targeting αvβ3 are finally discussed.

Magnetic nanoparticles in theranostic applications

Nanomedicine research recently started exploring the combination of therapy and diagnostics, so-called theranostics, as an approach to offer a more flexible, personal, and precise care with improved patient outcomes. As magnetic nanoparticles show great potential in a variety of diagnostic and therapeutic applications, they are prime candidates to be used in a theranostic platform to realize this vision. This Perspective gives an overview of state-of-the-art magnetic imaging techniques and theranostic applications based on magnetic nanoparticles and discusses their opportunities and associated challenges. In order to address these challenges and to exploit these opportunities to the fullest, we discuss three promising research directions. The first considers the use of novel magnetic field sequences to utilize the rich magnetic dynamics of the particles, allowing a more accurate diagnosis and boosting the performance of many nanoparticle-based applications. Second, we introduce the innovative concept of smart theranostics based on feedback mechanisms between the particle applications and their supporting imaging procedure to enhance the performance of both and to allow real-time monitoring of treatment efficiency. Finally, we show the twofold advantage of applying data-driven models to enhance therapy and diagnostics on the one hand and for handling the platform’s large amount of data and associated decision support algorithms on the other. The latter research track is extended to include hybrid models in which physics-based and data-driven models are combined to overcome challenges of applications with limited data, making the data-driven part understandable, as well as in uncovering unknown nanoparticle dynamics. Contrasting other literature works, which mainly focus on developing magnetic nanoparticles with the right characteristics, we put forward advances in magnetic nanoparticle imaging techniques and applications to enable the use of a broader range of magnetic nanoparticles in theranostics. We seek to emphasize the importance of these building blocks as many research opportunities with a very high potential are still left open. Therefore, we encourage researchers to also take these aspects into account to advance theranostic applications of magnetic nanoparticles to real clinical environments.

Update on Preclinical Development and Clinical Translation of Cholecystokinin-2 Receptor Targeting Radiopharmaceuticals.

Simple SummaryPeptide analogs, derived from the natural peptide hormone gastrin, are promising candidates for improving the visualization and treatment of tumors. Gastrin specifically binds to the cholecystokinin-2 receptor, a G-protein-coupled receptor expressed on the cell surface of different tumors. This enables specific targeting of tumor cells using gastrin analogs, labeled with radioisotopes. The receptor is expressed at high incidence in medullary thyroid carcinoma, a rare form of thyroid cancer lacking effective treatments at an advanced stage. Different radiolabeled gastrin analogs as well as nonpeptidic compounds targeting CCK2R have been developed. Specific modifications have been introduced in order to safely deliver the radiation to the tumor site. In this review, recent strategies applied to improve the targeting properties are described. These developments enabled the introduction of new radiolabeled peptide analogs for imaging and therapy in cancer patients. In addition to highlighting the current clinical trials, the perspectives for future applications are given.The cholecystokinin-2 receptor (CCK2R) has been a target of interest for molecular imaging and targeted radionuclide therapy for two decades. However, so far CCK2R targeted imaging and therapy has not been introduced in clinical practice. Within this review the recent radiopharmaceutical development of CCK2R targeting compounds and the ongoing clinical trials are presented. Currently, new gastrin derivatives as well as nonpeptidic substances are being developed to improve the properties for clinical use. A team of specialists from the field of radiopharmacy and nuclear medicine reviewed the available literature and summarized their own experiences in the development and clinical testing of CCK2R targeting radiopharmaceuticals. The recent clinical trials with novel radiolabeled minigastrin analogs demonstrate the potential for both applications, imaging as well as targeted radiotherapy, and reinforce the clinical applicability within a theranostic concept. The intense efforts in optimizing CCK2R targeting radiopharmaceuticals has led to new substances for clinical use, as shown in first imaging studies in patients with advanced medullary thyroid cancer. The first clinical results suggest that the wider clinical implication of CCK2R-targeted radiopharmaceuticals is reasonable.

Nuclear medicine theranostics comes of age.

Personalised medicine is widely discussed, but only intermittently implemented. The use of theranostics by whole body molecular imaging modalities (eg, 68Ga-prostate-specific membrane antigen [PSMA]-PET/CT or 68Ga-DOTATATE-PET/CT) allows assessment of druggable target expression as well as target accessibility of all lesions, defining patient populations that most likely benefit from radioligand therapy with their therapeutic counterparts 177Lu-PSMA and 177Lu-DOTATATE, respectively. Molecular imaging-based theranostics exclude patients from being exposed to a priori futile therapy. In the NETTER-1 trial 1 Strosberg J El-Haddad G Wolin E et al. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017; 376: 125-135 Crossref PubMed Scopus (1354) Google Scholar 177Lu-DOTATATE proved efficacious in rare neuroendocrine tumours, whereas the VISION trial 2 Sartor O de Bono J Chi KN et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385: 1091-1103 Crossref PubMed Scopus (170) Google Scholar studied a far more common cancer—prostate cancer, which is the second most common cause of cancer death in men—and showed 177Lu-PSMA was efficacious in this setting. Now that a significant benefit of 177Lu-PSMA has been shown in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer, with a median overall survival of 15·3 months versus 11·3 months for standard care (HR 0·62; 95% CI 0·52–0·74; p<0·001), 2 Sartor O de Bono J Chi KN et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385: 1091-1103 Crossref PubMed Scopus (170) Google Scholar the tone of the discussions around treatment has changed, with some advocating the disruption of the molecular imaging theranostic concept by discarding 68Ga-PSMA-PET/CT for patient selection. Correction to Lancet Oncol 2021; 22: 1497–98Herrmann K, Krause BJ, Hadaschik B, et al. Nuclear medicine theranostics comes of age. Lancet Oncol 2021; 22: 1497–98—In this Comment, the spelling of author Bernd Joachim Krause's surname was incorrectly spelt as “Kraus” and has been corrected to “Krause”. This correction has been made to the online version as of Nov 29, 2021. Full-Text PDF

Possible diagnostic pitfalls in 68Ga-PSMA PET/CT interpretation

Introduction/Aim 68 Ga-PSMA PET/CT is increasingly used in the evaluation of prostate cancer (PC), particularly in the detection and localization of disease recurrence. The main aim of the current study is to present physiological variation in distribution of PSMA activity and avidity in various benign and neoplastic conditions, as well as false-negative findings that may be misinterpreted. Materials and Methods PSMA represents an excellent biological target for high quality PET imaging of PC. However, PSMA uptake is not prostate-specific and is also expressed in other pathologic conditions. The causes of false-positive and false-negative 68 Ga-PSMA PET/CT findings are described. It is important for reporting physicians to recognize these findings. Results and Discussion PSMA is expressed in various benign and pathologic conditions. A wide range of malignancies other than PC have been reported to express PSMA as part of tumor neovasculature. Conclusion The nonexclusivity of PSMA avidity can potentially pave the way to expand the PSMA theranostic concept outside of PC.

Somatostatin receptor PET beyond the neuroendocrine tumors of the gastrointestinal tract - the review of literature.

PET of the somatostatine receptors (SSR) is a well-established functional imaging modality in the dia-gnosis of the neuroendocrine tumours (NET) of the gastro-entero-pancreatic origin (GEP). However, it can have a major impact also in other clinical entities. To present a literature review focusing on the effectivity of SSR PET in the dia-gnosis beyond GEP NET. SSR PET provides an accurate dia-gnosis of pulmonary NET, pheochromocytoma and paraganglioma, it may have an important impact on their treatment and clinical management. It allows a detailed estimation of the extent of meningeoma, contributes to precise target volumes for radiotherapy delineation and is sensitive in its residuum or recurrence detection. It can be a valuable method in the syndromes of multiple endocrine neoplasia and in the localization of the source of the ectopic Cushing syndrome. It can be used in the medullary thyroid cancer. An important role of SSR PET lies in the planning and monitoring of the peptide-receptor radionuclide therapy embraced in the theranostic concept.