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Background: Silver-111 is a promising β−-emitting radioisotope with ideal characteristics for targeted radionuclide therapy and associated single photon emission tomography imaging. Its decay properties closely resemble the clinically established lutetium-177, making it an attractive candidate for therapeutic applications. In addition, the clinical value of silver-111 is further enhanced by the existence of the positron-emitting counterpart silver-103, thus imparting a truly theranostic potential to this element. A so-fitting matching pair could potentially overcome the current limitations associated with the forced use of chemically different isotopes as imaging surrogates of lutetium-177, leading to more accurate and efficient diagnosis and treatment. However, the use of silver-111-based radiopharmaceuticals in vivo has faced obstacles due to the challenges related to its production and radiochemical separation from the target material. To address these issues, this study aims to implement a chromatographic separation methodology for the purification of reactor-produced silver-111. The ultimate goal is to achieve a ready-to-use formulation for the direct radiolabeling of tumour-seeking biomolecules. Results: A two-step sequence chromatographic process was validated for cold Ag-Pd separation and then translated to the radioactive counterpart. Silver-111 was produced via the 110Pd(n,γ)111Pd nuclear reaction on a natural palladium target and the subsequent β−-decay of palladium-111. Silver-111 was chemically separated from the metallic target via the implemented chromatographic process by using commercially available LN and TK200 resins. The effectiveness of the separations was assessed by inductively coupled plasma optical emission spectroscopy and γ-spectrometry, respectively, and the Ag+ retrieval was afforded in pure water. Recovery of silver-111 was > 90% with a radionuclidic purity > 99% and a separation factor of around 4.21·10−4. Conclusions: The developed separation method was suitable to obtain silver-111 with high molar activity in a ready-to-use water-based formulation that can be directly employed for the labeling of radiotracers. By successfully establishing a robust and efficient production and purification method for silver-111, this research paves the way for its wider application in targeted radionuclide therapy and precision imaging. [ABSTRACT FROM AUTHOR]

Globally, many individuals struggle with Alzheimer's disease (AD), an unrelenting and incapacitating neurodegenerative condition. Despite notable research endeavors, effective remedies for AD remain constrained, prompting the exploration of innovative therapeutic avenues. Within this context, silica-based nanoplatforms have emerged with pronounced potential due to their unique attributes like expansive surface area, customizable pore dimensions, and compatibility with living systems. These nanoplatforms hold promise as prospective interventions for AD. This assessment provides a comprehensive overview encompassing various forms of mesoporous silica nanoparticles (MSNs), techniques for formulation, and their applications in biomedicine. A significant feature lies in their ability to precisely guide and control the transport of therapeutic agents to the brain, facilitated by the adaptability of these nanoplatforms as drug carriers. Their utility as tools for early detection and monitoring of AD is investigated. Challenges and prospects associated with harnessing MSNs are studied, underscoring the imperative of stringent safety evaluations and optimization of how they interact with the body. Additionally, the incorporation of multifunctional attributes like imaging and targeting components is emphasized to enhance their efficacy within the intricate milieu of AD. As the battle against the profound repercussions of AD persists, MSNs emerge as a promising avenue with the potential to propel the development of viable therapeutic interventions. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is one of the most common causes of disability and mortality worldwide, creating a large socioeconomic burden annually. Secondary injury physiopathology is known to play a prominent role in exacerbating neurodegeneration post‐TBI and is potentially preventable by therapies. However, due to the heterogeneity of TBI and the complexity of the pathological mechanisms that ensue, there are currently no effective disease‐modifying treatments to prevent TBI‐associated disability and mortality. Nanotechnology has emerged in recent decades as a promising platform for the development of multifunctional neuroprotective agents for TBI. Herein, current multifunctional innovations are explored in this review in nanotechnology, which target the secondary injury pathological mechanisms of TBI and show promise in improving future post‐TBI management. Also, potential new directions for the future development of TBI treatment are discussed. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are found in many solid tumors, which play decisive roles in the occurrence, recurrence and metastasis of tumors. However, drugs are difficult to kill CSCs due to their limited number and location in oxygen-deprived tissue far from the blood vessels. Meanwhile, the survival and stemness maintenance of CSCs strongly depend on the tumor microenvironment (TME). Herein, we developed a CD44 antibody modified iridium nanosheet with enzyme-like activity (defined as Ir Nts-Ab) that effectively eradicates CSCs for cancer therapy. We observe that Ir Nts-Ab can enrich tumor tissues to remove excessive reactive oxygen species and produce oxygen, thus alleviating hypoxia and the inflammatory TME to reduce the proportion of CSCs and inhibit metastasis. In addition, Ir Nts-Ab targets CSCs and normal cancer cells with near infrared II-region photothermal therapy (NIR-II PTT), and is easily taken up by CSCs due to recognition of the CD44 proteins. Moreover, photoacoustic imaging helps monitor drug accumulation and hypoxic TME improvement in tumor tissue. Importantly, Ir Nts-Ab has good biological safety, making it suitable for biomedical applications. This iridium nanozyme based on TME regulation as well as NIR-II PTT will be a promising strategy for the treatment of cancer. Cancer stem cells (CSCs) are key factors that make tumors difficult to eradicate, and strongly depend on the hypoxic tumor microenvironment (TME), which plays a crucial role in the occurrence and metastasis of tumors. Herein, an antibody modified iridium nanosheet (definition as Ir Nts-Ab) was developed for targeted eradication of CSCs by photoacoustic imaging guided photothermal therapy (PTT) and TME regulation. Ir Nts-Ab with catalase-like activity could inhibit HIF-1α by producing oxygen, thus effectively reducing the proportion of CSCs and inhibiting tumor metastasis. Additionally, Ir Nts-Ab achieved the eradication of CSCs by PTT, and eliminated reactive oxygen species to decrease the inflammatory response, resulting in reduced tumor metastasis, which was promising for the cure of solid tumors in the clinics. [Display omitted] [ABSTRACT FROM AUTHOR]

In the past decades, for the intermediate or advanced cancerous stages, preclinical and clinical applications of nanomedicines in cancer theranostics have been extensively studied. Nevertheless, decreased specificity and poor targeting efficiency with low target concentration of theranostic are the major drawbacks of nanomedicine in employing clinical substitution over conventional systemic therapy. Consequently, ligand decorated nanocarrier-mediated targeted drug delivery system can transcend the obstructions through their enhanced retention activity and increased permeability with effective targeting. The highly efficient and specific nanocarrier-mediated ligand-based active therapy is one of the novel and promising approaches for delivery of the therapeutics for different cancers in recent years to restrict various cancer growth in vivo without harming healthy cells. The article encapsulates the features of nanocarrier-mediated ligands in augmentation of active targeting approaches of various cancers and summarizes ligand-based targeted delivery systems in treatment of cancer as plausible theranostics. [ABSTRACT FROM AUTHOR]

Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes. [ABSTRACT FROM AUTHOR]

Theranostic materials research is experiencing rapid growth driven by the interest in integrating both therapeutic and diagnostic modalities. These materials offer the unique capability to not only provide treatment but also track the progression of a disease. However, to create an ideal theranostic biomaterial without compromising drug encapsulation, diagnostic imaging must be optimized for improved sensitivity and spatial localization. Herein, we create a protein-engineered fluorinated coiled-coil fiber, Q2TFL, capable of improved sensitivity to 19F magnetic resonance spectroscopy (MRS) detection. Leveraging residue-specific noncanonical amino acid incorporation of trifluoroleucine (TFL) into the coiled-coil, Q2, which self-assembles into nanofibers, we generate Q2TFL. We demonstrate that fluorination results in a greater increase in thermostability and 19F magnetic resonance detection compared to the nonfluorinated parent, Q2. Q2TFL also exhibits linear ratiometric 19F MRS thermoresponsiveness, allowing it to act as a temperature probe. Furthermore, we explore the ability of Q2TFL to encapsulate the anti-inflammatory small molecule, curcumin (CCM), and its impact on the coiled-coil structure. Q2TFL also provides hyposignal contrast in 1H MRI, echogenic signal with high-frequency ultrasound and sensitive detection by 19F MRS in vivo illustrating fluorination of coiled-coils for supramolecular assembly and their use with 1H MRI, 19F MRS and high frequency ultrasound as multimodal theranostic agents. [ABSTRACT FROM AUTHOR]

Currently, spatiotemporal theranostic nanoprobes are in great demand, owing to their enhanced target therapy and precise dynamic tracing of in vivo drug fate. Herein, this study highlights the successful development of dynamic theranostic nanoprobes, which are facilely established via self‐assembly between glutathione (GSH)‐responsive dasatinib (DAS) dimers and indocyanine green (ICG). The DAS dimers endow the nanoprobes with aggregation‐induced emission (AIE) characteristic, whose emission wavelength successfully redshifts from 420 to 810 nm compared to DAS‐based nanoprobes, the same as that of ICG, thus improving the total fluorescence intensity. Moreover, the nanoprobes exhibit a dynamic fluorescence intensity conversion that first decreases and then increases at the tumor site via intracellular GSH‐triggered AIE quenching and fluorescence re‐enhancement of ICG, therefore achieving precise tumor diagnosis, prognosis evaluation, and spatiotemporal tracing of drug fate compared to other imaging strategies. Furthermore, the nanoprobes show long‐term circulation stability via suitable particle sizes and zeta potentials, improved tumor accumulation via extracellular protonation and active cellular uptake, efficient drug release via response to the intracellular milieu, and enhanced apoptosis via targeting to intracellular kinase, therefore achieving the significant tumor inhibition. Thus, the spatiotemporal theranostic nanoprobes can dynamically monitor the targeted tumor therapy, greatly advancing their application in clinics. [ABSTRACT FROM AUTHOR]

MRI contrast agents are required in the clinic to detect some pathologies, such as cancers. Nevertheless, at the moment, only small extracellular and non-specific gadolinium complexes are available for clinicians. Moreover, safety issues have recently emerged concerning the use of gadolinium complexes; hence, alternatives are urgently needed. Manganese-based MRI contrast agents could be one of these alternatives and increasing numbers of studies are available in the literature. This review aims at synthesizing all the research, from small Mn complexes to nanoparticular agents, including theranostic agents, to highlight all the efforts already made by the scientific community to obtain highly efficient agents but also evidence of the weaknesses of the developed systems. [ABSTRACT FROM AUTHOR]

Objectives: Zinc sulfide nanoparticles (ZnS NPs), as one of the quantum dots less than 10 nm, possess unique size‐dependent autofluorescence. Excitation of their valence electrons by energy higher than the bandgap reveals the ZnS NPs' inherited photocatalysis with additive cytotoxic consequences of reactive oxygen species (ROS) release. Coupling the cytotoxicity of photoactivated ZnS NPs with their autofluorescence would be a novel theranostic modality, combating superficially accessible carcinoma. Material and methods: After synthesizing and characterization of ZnS NPs, we verified their photocatalysis and electron donation upon UV excitation in degrading organic dye and DNA cleavage, respectively. We then tested the efficacy of UV‐activated ZnS NPs to induce ROS‐dependent apoptosis in squamous cell carcinoma and breast cancer cell lines. Results: The energetic electron–hole pairs generated upon UV excitation of ZnS NPs with the consequent cascade of ROS release revealed potent apoptotic cancer cell deaths, compared with single treatment modalities of nonexcited nanoparticles and UV. Moreover, the inherited luminescence of ZnS NPs enabled visualization of their predominant intracytoplasmic uptake with tracking of their cellular response. Conclusion: The intensified luminescence and the fortified cytotoxicity of photoactivated ZnS NPs enhance their theranostic qualifications, boosting their antitumorigenic use. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has recently become significant as a clinical modality for cancer therapy and multidrug-resistant (MDR) infections, replacing conventional chemotherapy and radiation therapy protocols. PDT involves the excitation of certain nontoxic molecules called photosensitizers (PS), applying a specific wavelength of light to generate reactive oxygen species (ROS) to treat cancer cells and other pathogens. Rhodamine 6G (R6G) is a well-known laser dye with poor aqueous solubility, and lower sensitivity poses an issue in using PS for PDT. Nanocarrier systems are needed to deliver R6G to cancer targets since PDT requires a higher accumulation of PS. It was found that R6G-conjugated gold nanoparticles (AuNP) have a higher ROS quantum yield of 0.92 compared to 0.3 in an aqueous R6G solution, increasing their potency as PS. Cytotoxicity assessment on A549 cells and antibacterial assay on MDR Pseudomonas aeruginosa collected from a sewage treatment plant are the evidence to support efficient PDT. In addition to their enhanced quantum yields, the decorated particles are effective in generating fluorescent signals that can be used for cellular imaging and real-time optical imaging, and the presence of AuNP is a valuable addition to CT imaging. Furthermore, the fabricated particle exhibits anti-Stokes properties, which makes it suitable for use as a background-free biological imaging agent. As a result, R6G-conjugated AuNP is an effective theranostic agent that prevents the progression of cancer and MDR bacteria, along with contrasting abilities in medical imaging with minimal toxicity observed in in vitro and in vivo assays using zebrafish embryos. [ABSTRACT FROM AUTHOR]

Despite advances in diagnostic and therapeutic technologies for cardiovascular diseases (CVDs), it remains a leading cause of mortality and morbidity worldwide. This underscores the urgency for innovative approaches aiming at early and precise detection and treatment of CVDs to reduce the disease burden. Iron oxide nanoparticles (IONPs), with their unique magnetism and bioproperties, have shown great potential in this regard. In this review, we will begin with a brief overview of the synthesis and properties of IONPs. We will then focus on the latest applications of IONPs in CVDs, including diagnosis and treatment. The use of IONPs in the integration of diagnosis and treatment for CVDs is a promising field, and will be addressed in a separate section. The translational potential and challenges of IONPs will also be discussed. In conclusion, ongoing research and development of IONP-based strategies are highly likely to address current challenges effectively, and offer more personalized and efficient options for the diagnosis and treatment of CVDs. [ABSTRACT FROM AUTHOR]

Introduction/Justification: Head and neck squamous cell carcinoma (HNSCC) represents a serious health problem worldwide. Approximately 75% of patients with HNSCC have locally advanced disease at diagnosis, and the therapy for those cases involves chemoradiation or induction chemotherapy, in which cisplatin is included despite of its substantial side effects. FAPESP-founded “Cancer Innovation Center with Emphasis on Metals and Theranostics” (CancerThera) is dedicated to the development of new metallopharmaceuticals and radiopharmaceuticals for tumor diagnosis and treatment. Among these developments, an anti-integrin peptide modified by a conventional spacer (C6) and chelator (DOTA) was evaluated as a potential treatment of HNSCC. Overexpressed in HNC, integrins are transmembrane proteins that play essential roles in cell proliferation and migration. Therefore, integrin inhibition may be a potential targeted therapy for HNC patients. Objectives: The study aimed to evaluate the effects of the DOTA-C6-anti-integrin peptide on HNSCC cell lines proliferation and migration, as an initial step for HNSCC theranostic development. Materials and Methods: The anti-proliferative activity of the DOTA-C6-anti-integrin peptide (0.01nM - 100µM) was assessed against FaDu and SCC-25 cells by considering the cell amounts at baseline and 48h after exposure (two untreated control groups). All cells were fixed with 50% trichloroacetic acid and stained with sulforhodamine B. Spectrophotometric absorbance was performed at 540nm in a microplate reader. Cell migration was assessed in FaDu cells and FaDu cells treated with the DOTA-C6-anti-integrin peptide (1, 10, and 100µM) using the wound-healing assay. Wound cells were photographed immediately (0h) and after 16h, 24h, and 40h. Images were analyzed by the ImageJ software (National Institutes of Health). For statistical analysis, samples did assume normal distribution in Shapiro-Wilk's test, thus we used t test to compare the groups using SPSS 21 software (SPSS Incorporation). Results: At the tested concentration range, the DOTA-C6-anti-integrin peptide did not affect proliferation of FaDu or SCC-25 cells. In FaDu cells, the DOTA-C6-anti-integrin peptide significantly (p < 0.05) inhibited migration in comparison to untreated cells, independent on sample concentration (1, 10, and 100µM) or time exposure (16, 24, or 40 h). Conclusion: Despite the lack of anti-proliferative effect, the DOTA-C6-anti-integrin peptide inhibited migration in FaDu cells. As cell migration is an important process in HNSCC progression, our data present preliminary evidence that the DOTA-C6-anti-integrin may be used in development of theranostic agents for HNSCC. Acknowledgements: The study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNP #429463/2018-9), Fundação de Apoio ao Ensino e à Pesquisa do Estado de São Paulo (FAPESP #2023/09738-4, FAPESP #2023/012810-9, Cancer Theranostics Innovation Center, (CancerThera), CEPID FAPESP #2021/10265-8), and International Atomic Energy Agency (IAEA) technical cooperation projects for development of Latin American Countries (IAEA/TCLAC: EX-BRA6033-2401375).

Introduction/Justification: Sarcomas are malignant tumors in the bone, cartilage, fat, muscles, and vessels. Sar- comas are highly heterogeneous due to the wide variety of histological subtypes and various ana- tomical locations, and thus, the diagnosis and management of these tumors are challenging. Beyond sarcomas, the musculoskeletal system is a frequent site of metastatic tumors and multiple myeloma with lesions that present difficult local control. Imaging exams such as MRI and 18F-FDG (FDG PET/CT) to assess the extent of these tumors play a crucial role in managing these patients. How- ever, PET/CT imaging with 18F-PSMA-1007 (PSMA PET/CT) may be a more interesting diagnostic marker due to the potential Theranostics implications. Objectives: This study aimed to compare the performance of FDG PET/CT and PSMA PET/CT images in patients with advanced-stage unresectable recurrent and metastatic musculoskeletal tumors. Materials and Methods: Patients underwent FDG PET/CT and PSMA PET/CT imaging with a 24-hour interval be- tween studies. Two nuclear medicine physicians compared imaging findings. Results: Eight patients underwent FDG PET/CT and PSMA PET/CT images. In five patients, PSMA uptake was higher than FDG uptake. The highest PSMA uptake occurred in a giant cell recurrent sacral tumor of a 27-year-old male patient; the SUVs for PSMA and FDG were 100 and 16, respec- tively. A 58-year-old male patient with osteolytic metastasis from renal cell carcinoma in the right scapula presented PSMA uptake higher than FDG (SUVs = 40 and 11, respectively). A recurrent spin- dle cell neural tumor in the upper limb of a 69-year-old male presented PSMA uptake also higher than FDG (SUVs = 27 and 8, respectively). A myxofibrosarcoma mass in the distal right leg of a 61- year-old female presented higher PSMA uptake slightly higher than FDG uptake (SUVs = 18 and 10, respectively). Interestingly, two patients with chordomas had heterogeneous PSMA and FDG up- take. The PSMA PET/CT of a 65-year-old male patient presenting multiple metastases from chor- doma with soft tissue invasion showed uptake higher than FDG in all lesions; the highest SUV was a lesion in the right acetabulum: PSMA SUV = 32 and FDG SUV = 19. This patient presented PSMA-avid additional sites of metastases in mediastinal lymph nodes and the right hepatic lobe, while FDG uptake was minimal in these metastases. In contrast, an FDG PET/CT of a 54-year-old male with a large recurrent chordoma (30x24 cm mass) extending from the level of L4 to the proximal left thigh presented FDG uptake higher than PSMA uptake (SUVs = 31 and 9, respectively). Also, FDG uptake of two patients (52-year-old males) with desmoid tumors in the upper limb was higher than PSMA uptake, although uptake of both radiotracers was low: PSMA SUVs of 3 and 5, and FDG SUVs of 4 and 7. Conclusion: The study results show the potential advantage of using PSMA PET/CT and FDG PET/CT to provide additional information for monitoring patients and combining therapies, especially as PSMA PET/CT demonstrated more extensive disease. PSMA PET/CT has the advantage of the possi- bility of a Theranostic approach.

Introduction/Justification: Lung cancer remains a major global cause of mortality. While 18F-FDG PET/CT is widely utilized for detection, staging, and monitoring, detecting increased glucose metabolism in tumor cells, it lacks theranostic potential. The prostate-specific membrane antigen (PSMA) tracer, initially linked to prostate cancer, is also recognized as a marker of neoangiogenesis, accumulating in various neoplasms and showing promising theranostic capabilities. Objectives: This study aims to compare the uptake patterns of 18F-FDG and 18F-PSMA in primary and metastatic lesions of non-small cell lung cancer. Materials and Methods: Four male patients diagnosed with non-small cell lung cancer (including two adenocarcinomas, one squamous cell carcinoma, and one unspecified type), aged between 58 and 71 years, underwent PET/CT imaging. 18F-FDG PET/CT scans were performed 60 minutes after intravenous administration of 0.1 mCi/kg of 18F-FDG, while 18F-PSMA PET/CT scans were obtained 90 minutes after intravenous injection of 0.1 mCi/kg of 18F-PSMA. Imaging data were analyzed by two nuclear medicine physicians and one radiologist. The maximum standardized uptake value (SUVmax) of each lesion was measured for both radiotracers in the primary tumor, lymph nodes, and metastatic sites identified through visual analysis, considering values obtained above the cardiac blood pool measured in the left atrium. Results: A total of 100 lesions were detected, with 82 identified using 18F-FDG and 92 using 18F-PSMA. Eight lesions were exclusively detected by 18F-FDG, while 14 were only identified by 18F-PSMA. The median SUVmax of lesions in 18F-FDG and 18F-PSMA images was 5.3 (1.7 – 25.0) and 3.7 (0.7 - 12.4), respectively. Brain lesions were more readily identified on 18F-PSMA images, whereas liver lesions were more notable on 18F-FDG images due to the intense physiological uptake of 18F-FDG and 18F-PSMA in the brain and liver, respectively. Conclusion: Both 18F-FDG-PET/CT and 18F-PSMA-PET/CT have the ability to identify most lesions of non-small cell lung cancer. Although 18F-PSMA images detected a greater number of lesions, the uptake intensity is generally higher with 18F-FDG. These findings suggest that the two radiopharmaceuticals may have complementary roles in lung cancer by independently detecting lesions with higher glycolytic activity or greater neoangiogenesis, or both simultaneously, which could contribute to a more personalized approach in managing these patients. The results also suggest a possible theranostic approach in selected patients with high uptake of PSMA. Further investigations involving a larger patient cohort are essential to validate these findings.

Introduction/Justification: Triple-refractory multiple myeloma (MM) has a poor prognosis. It is a neoplasm with marked genomic heterogeneity, and recently, our group demonstrated marked uptake of 68Ga-PSMA-11 in some patients, suggesting the potential theranostic use of PSMA in selected cases (1). Herein, we report the initial treatment with 177Lu-PSMA in a patient with refractory MM. Report: A 76-year-old male patient with IgA/Kappa MM refractory to 6 therapeutic lines, including daratumumab, lenalidomide, and bortezomib, underwent PET/CT with 18F-PSMA-1007, showing marked tracer uptake in multiple osteolytic lesions, several with extensive soft tissue components. A PET/CT with 18F-FDG was also performed, revealing similar findings. A first dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T was administered. The procedure was well tolerated, with slight clinical improvement observed in the week following the infusion. Visual analysis of whole-body scans performed at 21h, 30h, and 7 days demonstrated moderate tracer uptake, lower than that observed with 18F-PSMA-1007. There was slight washout between images at 21h and 30h and moderate/significant washout after 7 days. After 4 weeks, PET/CTs with 18F-PSMA and 18F-FDG were repeated, showing similar findings to the initial scans, with a slight reduction in tracer uptake in some lesions. There was also an increase in the volume of some soft tissue lesions, attributed to post-treatment inflammation. The patient received a second dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T after 6 weeks, and whole-body scans were performed at 2h and 24h, also showing visually lower uptake compared to 18F-PSMA-1007. The patient experienced an intercurrent femoral fracture, limiting mobility for clinical evaluation and subsequent procedures, ultimately leading to their passing after a few days. Conclusion: This preliminary report suggests that treatment of MM with 177Lu-PSMA is feasible and well tolerated after 2 initial doses. The uptake of 177Lu-PSMA-I&T was visually lower than that of 18F-PSMA-1007, which does not seem to be solely explained by the different resolution of images obtained from different tracers and equipment. There was a slight clinical and imaging response after the first dose, out of a total of 6 planned. A fracture complication and the severity of the case prevented imaging evaluation after the 2nd dose and further treatment continuation. PSMA-177Lu therapy in MM treatment appears to be safe with an initial favorable response, albeit slight. Studies with complete treatments (6 cycles) and in clinically less severe patients are needed to assess the effectiveness of the procedure.

Abstract Background The aim of this study was to investigate the quantification performance of a 360° CZT camera for 177Lu-based treatment monitoring. Methods Three phantoms with known 177Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data. Results Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for 177Lu-PSMA patients in 2–3 times faster than the time taken for a conventional gamma camera. Conclusion Quantification of whole-body 3D images of patients treated with 177Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT.

Photothermal therapy (PTT) can overcome cancer treatment resistance by enhancing the cell membrane permeability, facilitating drug accumulation, and promoting drug release within the tumor tissue. Iron oxide nanoparticles (IONPs) have emerged as effective agents for PTT due to their unique properties and biocompatibility. Approved for the treatment of anemia, as MRI contrast agents, and as magnetic hyperthermia mediators, IONPs also offer excellent light-to-heat conversion and can be manipulated using external magnetic fields for targeted accumulation in specific tissue. Optimizing parameters such as the laser wavelength, power density, shape, size, iron oxidation state, functionalization, and concentration is crucial for IONPs’ effectiveness. In addition to PTT, IONPs enhance other cancer treatment modalities. They improve tumor oxygenation, enhancing the efficacy of radiotherapy and photodynamic therapy. IONPs can also trigger ferroptosis, a programmed cell death pathway mediated by iron-dependent lipid peroxidation. Their magneto-mechanical effect allows them to exert a mechanical force on cancer cells to destroy tumors, minimizing the damage to healthy tissue. This review outlines strategies for the management of the photothermal performance and PTT efficiency with iron oxide nanoparticles, as well as synergies with other cancer therapies.

Since the discovery of cisplatin’s antitumoral activity and its approval as an anticancer drug, significant efforts have been made to enhance its physiological stability and anticancer efficacy and to reduce its side effects. With the rapid development of targeted and personalized therapies, and the promising theranostic approach, platinum drugs have found new opportunities in more sophisticated systems. Theranostic agents combine diagnostic and therapeutic moieties in one scaffold, enabling simultaneous disease monitoring, therapy delivery, response tracking, and treatment efficacy evaluation. In these systems, the platinum core serves as the therapeutic agent, while the functionalized ligand provides diagnostic tools using various imaging techniques. This review aims to highlight the significant role of platinum–based complexes in theranostic applications, and, to the best of our knowledge, this is the first focused contribution on this type of platinum compounds. This review presents a brief introduction to the development of platinum chemotherapeutic drugs, their limitations, and resistance mechanisms. It then describes recent advancements in integrating platinum complexes with diagnostic agents for both tumor treatment and monitoring. The main body is organized into three categories based on imaging techniques: fluorescence, positron emission tomography (PET), single–photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Finally, this review outlines promising strategies and future perspectives in this evolving field.

Abstract The development of diagnostic and therapeutic radiopharmaceuticals is an hot topic in nuclear medicine. Several radiolabeled antibodies are under development necessitating both biokinetic and dosimetry extrapolations for effective human translation. The validation of different animal-to-human dosimetry extrapolation methods still is an open issue. This study reports the mice-to-human dosimetry extrapolation of 64Cu/177Lu 1C1m-Fc anti-TEM-1 for theranostic application in soft-tissue sarcomas. We adopt four methods; direct mice-to-human extrapolation (M1); dosimetry extrapolation considering a relative mass scaling factor (M2), application of a metabolic scaling factor (M3) and combination of M2 and M3 (M4). Predicted in-human dosimetry for the [64Cu]Cu-1C1m-Fc resulted in an effective dose of 0.05 mSv/MBq. Absorbed dose (AD) extrapolation for the [177Lu]Lu-1C1m-Fc indicated that the AD of 2 Gy and 4 Gy to the red-marrow and total-body can be reached with 5–10 GBq and 25–30 GBq of therapeutic activity administration respectively depending on applied dosimetry method. Dosimetry extrapolation methods provided significantly different absorbed doses in organs. Dosimetry properties for the [64Cu]Cu-1C1m-Fc are suitable for a diagnostic in-human use. The therapeutic application of [177Lu]Lu-1C1m-Fc presents challenges and would benefit from further assessments in animals’ models such as dogs before moving into the clinic.

Abstract Bacteria can colonize a variety of in vivo biointerfaces, particularly the skin, nasal, and oral mucosa, the gastrointestinal tract, and the reproductive tract, but also target specific lesion sites, such as tumor and wound. By virtue of their prominent characteristics in motility, editability, and targeting ability, bacteria carrying imageable agents are widely developed as living probes for bioimaging and diagnosis of different diseases. This review first introduces the strategies used for preparing bacteria‐based living probes, including biological engineering, chemical modification, intracellular loading, and optical manipulation. It then summarizes the recent progress of these living probes for fluorescence imaging, near‐infrared imaging, ultrasonic imaging, photoacoustic imaging, magnetic resonance imaging, and positron emission tomography imaging. The biomedical applications of bacteria‐based living probes are also reviewed particularly in the bioimaging and diagnosis of bacterial infections, cancers, and intestine‐associated diseases. In addition, the advantages and challenges of bacteria‐based living probes are discussed and future perspectives are also proposed. This review provides an updated overview of bacteria‐based living probes, highlighting their great potential as a unique yet versatile platform for developing next‐generation imageable agents for intelligent bioimaging, diagnosis, and even therapy.

The application of nanotechnology to cancer research has resulted in substantial advancements. In this study, gold nanoparticles (AuNPs) synthesised utilising environmentally friendly methods are evaluated for their potential as multipurpose theranostic agents in cancer treatment. These eco-friendly AuNPs are attractive candidates for theranostic applications that combine diagnosis and therapy due to their specific physicochemical features. Green nanotechnology practises that use only sustainable, biocompatible materials promote biocompatibility in biomedical applications while reducing environmental impact. Imaging techniques such as optical coherence tomography, surface-enhanced Raman scattering, and photoacoustic imaging can benefit from AuNPs in part due to their optical properties. Their surface plasmon resonance (SPR) can be adjusted, improving imaging contrast and allowing for tailored administration of therapeutic payloads. The localised SPR effect of AuNPs also increases the efficacy of photothermal treatment (PTT) by converting near-infrared light into localised heat and inducing hyperthermia in cancer cells. Because of the localised heating, the cancer may be ablated precisely and with minimal collateral damage. AuNPs can be observed and assessed in real time as part of a multimodal imaging platform, in addition to being used as diagnostic and therapeutic tools. The primary focus of this research is on recent breakthroughs in the production of AuNPs using green nanotechnology techniques, particularly those that have occurred beyond 2020, and their potential applications in cancer theranostics. We are investigating various techniques for functionalizing AuNPs with specific ligands, medications, and imaging agents in order to improve therapeutic efficacy. We also go over the regulatory considerations and toxicity assessments that must be considered when bringing these nanomaterials into clinical use, as well as the potential that exist.

Abstract With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state‐of‐art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications.

Traumatic brain injury (TBI) is one of the most common causes of disability and mortality worldwide, creating a large socioeconomic burden annually. Secondary injury physiopathology is known to play a prominent role in exacerbating neurodegeneration post‐TBI and is potentially preventable by therapies. However, due to the heterogeneity of TBI and the complexity of the pathological mechanisms that ensue, there are currently no effective disease‐modifying treatments to prevent TBI‐associated disability and mortality. Nanotechnology has emerged in recent decades as a promising platform for the development of multifunctional neuroprotective agents for TBI. Herein, current multifunctional innovations are explored in this review in nanotechnology, which target the secondary injury pathological mechanisms of TBI and show promise in improving future post‐TBI management. Also, potential new directions for the future development of TBI treatment are discussed.

Rhenium-186 (186Re) labeled nanoliposome (RNL) therapy for recurrent glioblastoma patients has shown promise to improve outcomes by locally delivering radiation to affected areas. To optimize the delivery of RNL, we have developed a framework to predict patient-specific response to RNL using image-guided mathematical models. Methods: We calibrated a family of reaction-diffusion type models with multi-modality imaging data from ten patients (NCR01906385) to predict the spatio-temporal dynamics of each patient's tumor. The data consisted of longitudinal magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) to estimate tumor burden and local RNL activity, respectively. The optimal model from the family was selected and used to predict future growth. A simplified version of the model was used in a leave-one-out analysis to predict the development of an individual patient's tumor, based on cohort parameters. Results: Across the cohort, predictions using patient-specific parameters with the selected model were able to achieve Spearman correlation coefficients (SCC) of 0.98 and 0.93 for tumor volume and total cell number, respectively, when compared to the measured data. Predictions utilizing the leave-one-out method achieved SCCs of 0.89 and 0.88 for volume and total cell number across the population, respectively. Conclusion: We have shown that patient-specific calibrations of a biology-based mathematical model can be used to make early predictions of response to RNL therapy. Furthermore, the leave-one-out framework indicates that radiation doses determined by SPECT can be used to assign model parameters to make predictions directly following the conclusion of RNL treatment. Statement of Significance: This manuscript explores the application of computational models to predict response to radionuclide therapy in glioblastoma. There are few, to our knowledge, examples of mathematical models used in clinical radionuclide therapy. We have tested a family of models to determine the applicability of different radiation coupling terms for response to the localized radiation delivery. We show that with patient-specific parameter estimation, we can make accurate predictions of future glioblastoma response to the treatment. As a comparison, we have shown that population trends in response can be used to forecast growth from the moment the treatment has been delivered.In addition to the high simulation and prediction accuracy our modeling methods have achieved, the evaluation of a family of models has given insight into the response dynamics of radionuclide therapy. These dynamics, while different than we had initially hypothesized, should encourage future imaging studies involving high dosage radiation treatments, with specific emphasis on the local immune and vascular response.

AbstractCancer is a devastating health problem with inadequate treatment options. Many conventional treatments for solid-tumor cancers lack tumor specificity, which results in low efficacy and off-target damage to healthy tissues. Nanoparticle (NP)-mediated photothermal therapy (PTT) is a promising minimally invasive treatment for solid-tumor cancers that has entered clinical trials. Traditionally, NPs used for PTT are coated with passivating agents and/or targeting ligands, but alternative coatings are being explored to enhance tumor specific delivery. In particular, cell-derived membranes have emerged as promising coatings that improve the biointerfacing of photoactive NPs, which reduces their immune recognition, prolongs their systemic circulation and increases their tumor accumulation, allowing for more effective PTT. To maximize treatment success, membrane-wrapped nanoparticles (MWNPs) that enable dual tumor imaging and PTT are being explored. These multifunctional theranostic NPs can be used to enhance tumor detection and/or ensure a sufficient quantity of NPs that have arrived in the tumor prior to laser irradiation. This review summarizes the current state-of-the-art in engineering MWNPs for combination cancer imaging and PTT and discusses considerations for the path toward clinical translation.

Atherosclerotic plaque remains the primary cause of morbidity and mortality worldwide. Accurate assessment of the degree of atherosclerotic plaque is critical for predicting the risk of atherosclerotic plaque and monitoring the results after intervention. Compared with traditional technology, the imaging technologies of nanoparticles have distinct advantages and great development prospects in the identification and characterization of vulnerable atherosclerotic plaque. Here, we systematically summarize the latest advances of targeted nanoparticle approaches in the diagnosis of atherosclerotic plaque, including multimodal imaging, fluorescence imaging, photoacoustic imaging, exosome diagnosis, and highlighted the theranostic progress as a new therapeutic strategy. Finally, we discuss the major challenges that need to be addressed for future development and clinical transformation.

The pharmacological activity of organotin(IV) complexes in cancer therapy is well recognized but their large applicability is hampered by their poor water solubility. Hence, carbon dots, in particular nitrogen‐doped graphene quantum dots (NGQDs), may be a promising alternative for the efficient delivery of organotin(IV) compounds as they have a substantial aqueous solubility, a good chemical stability, and non‐toxicity as well as a bright photoluminescence that make them ideal for theranostic applications against cancer. Two different multifunctional nanosystems have been synthesized and fully characterized based on two fragments of organotin‐based cytotoxic compounds and 4‐formylbenzoic acid (FBA), covalently grafted onto the NGQDs surface. Subsequently, an in vitro determination of the therapeutic and theranostic potential of the achieved multifunctional systems was carried out. The results showed a high cytotoxic potential of the NGQDs‐FBA‐Sn materials against breast cancer cell line (MDA‐MB‐231) and a lower effect on a non‐cancer cell line (kidney cells, HEK293T). Besides, thanks to their optical properties, the dots enabled their fluorescence molecular imaging in the cytoplasmatic region of the cells pointing towards a successful cellular uptake and a release of the metallodrug inside cancer cells (NGQDs‐FBA‐Sn). [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [225Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs). Methods: This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [225Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [225Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [68Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria. Results: Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [177Lu]Lu-DOTATATE. [225Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [68Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months. Conclusion: The preliminary results of this study suggest that [225Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [177Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects. [ABSTRACT FROM AUTHOR]

This study presents the synthesis of glucosamine-modified mesoporous silica-coated magnetic nanoparticles (MNPs) as a therapeutic platform for the delivery of an anticancer drug, methotrexate (MTX). The MNPs were coated with mesoporous silica in a templated sol–gel process to form MNP@MSN, and then chloropropyl groups were added to the structure in a post-modification reaction. Glucosamine was then reacted with the chloro-modified structure, and methotrexate was conjugated to the hydroxyl group of the glucose. The prepared structure was characterized using techniques such as Fourier transform infrared (FT-IR) spectroscopy, elemental analysis (CHN), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), a vibrating sample magnetometer (VSM), and X-ray diffraction (XRD). Good formation of nano-sized MNPs and MNP@MSN was observed via particle size monitoring. The modified glucosamine structure showed a controlled release profile of methotrexate in simulated tumor fluid. In vitro evaluation using the 4T1 breast cancer cell line showed the cytotoxicity, apoptosis, and cell cycle effects of methotrexate. The MTT assay showed comparable toxicity between MTX-loaded nanoparticles and free MTX. The structure could act as a glucose transporter-targeting agent and showed increased uptake in cancer cells. An in vivo breast cancer model was established in BALB/C mice, and the distribution of MTX-conjugated MNP@MSN particles was visualized using MRI. The MTX-conjugated particles showed significant anti-tumor potential together with MRI contrast enhancement. [ABSTRACT FROM AUTHOR]

Objective: Magnetic nanoparticles (MNPs) are considered a theranostic agent in MR imaging, playing an effective role in inducing magnetic hyperthermia. Since, high-performance magnetic theranostic agents are characterized by superparamagnetic behavior and high anisotropy, in this study, cobalt ferrite MNPs were optimized and investigated as a theranostic agent. Methods: CoFe2O4@Au@dextran particles were synthesized and characterized by DLS, HRTEM, SEM, XRD, FTIR, and VSM methods. After cytotoxicity evaluation, MR imaging parameters (r1, r2 and r2 / r1) were calculated for these nanostructures. Afterward, magnetic hyperthermia at the frequency of 425 kHz was applied to calculate specific loss power (SLP). Results: Formation of CoFe2O4@Au@dextran was confirmed by UV–Visible spectrophotometry. On the basis of the relaxometric and hyperthermia induction findings of nanostructures in all stages of synthesis, the CoFe2O4@Au@dextran could produce the highest parameters of r2 and r2/r1 and SLP with values ​​of 389.7, 51.2 mM−1 s−1, and 2449 W/g, respectively. Conclusion: The formation of multi-core MNPs by dextran coating is expected to improve the magnetic properties of the nanostructure, leading to optimization of theranostic parameters, so that CoFe2O4@Au@dextran NPs can create contrast-enhanced images more than three times the clinical use and require less contrast agent, reducing side effects. Accordingly, CoFe2O4@Au@dextran can be introduced as a suitable theranostic nanostructure with optimal efficiency. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the quantification performance of a 360° CZT camera for 177Lu-based treatment monitoring. Methods: Three phantoms with known 177Lu activity concentrations were acquired: (1) a uniform cylindrical phantom for calibration, (2) a NEMA IEC body phantom for analysis of different-sized spheres to optimise quantification parameters and (3) a phantom containing two large vials simulating organs at risk for tests. Four sets of reconstruction parameters were tested: (1) Scatter, (2) Scatter and Point Spread Function Recovery (PSFR), (3) PSFR only and (4) Penalised likelihood option and Scatter, varying the number of updates (iterations × subsets) with CT-based attenuation correction only. For each, activity concentration (ARC) and contrast recovery coefficients (CRC) were estimated as well as root mean square. Visualisation and quantification parameters were applied to reconstructed patient image data. Results: Optimised quantification parameters were determined to be: CT-based attenuation correction, scatter correction, 12 iterations, 8 subsets and no filter. ARC, CRC and RMS results were dependant on the methodology used for calculations. Two different reconstruction parameters were recommended for visualisation and for quantification. 3D whole-body SPECT images were acquired and reconstructed for 177Lu-PSMA patients in 2–3 times faster than the time taken for a conventional gamma camera. Conclusion: Quantification of whole-body 3D images of patients treated with 177Lu-PSMA is feasible and an optimised set of parameters has been determined. This camera greatly reduces procedure time for whole-body SPECT. [ABSTRACT FROM AUTHOR]

Reirradiation of the spine is carried out in 42% of patients who do not respond to treatment or have recurrent pain. However, there are few studies and data on the effect of reirradiation of the spine and the occurrence of acute and chronic side-effects caused by reirradiation, such as myelopathy, in these patients. This meta-analysis aimed to determine the safe dose in terms of biological effective dose (BED), cumulative dose and dose interval between BED 1 and BED 2 to decrease or prevent myelopathy and pain control in patients undergoing radiation therapy in the spinal cord. A search was carried out using EMBASE, MEDLINE, PUBMED, Google Scholar, Cochrane Collaboration library electronic databases, Magiran, and SID from 2000 to 2022 to recognise qualified studies. In total, 17 primary studies were applied to estimate the pooled effect size. The random effects model showed that the pooled BED in the first stage, the BED in the second stage and the cumulative BED 1 and BED 2 were estimated at 77.63, 58.35 and 115.34 Gy, respectively. Studies reported on dose interval. The results of a random effects model showed that the pooled interval was estimated at 13.86 months. The meta-analysis revealed that using appropriate BED 1 and/or BED 2 in a safe interval between the first and second phases of treatment can have an influential role in preventing or reducing the effects of myelopathy and regional control pain in spinal reirradiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, the diagnosis of salivary gland tumors using current imaging techniques is unreliable. In this study we examined salivary gland tumors and discovered that the pleomorphic adenoma, a tumor which should be surgically removed because it has a tendency to become malign, has a strong concentration of the somatostatin receptor 2. This characteristic may allow physicians to identify and potentially treat the tumor in a non-invasive manner. Reliable preoperative diagnosis between salivary gland tumor entities is difficult. In this monocentric retrospective study, we examined the somatostatin receptor 2 (SSTR2) status of salivary gland tumors after salivary gland tumor resection via immunohistochemistry (IHC), and stains were compared in analogy to the HER2 mamma scale. A total of 42.3% of all pleomorphic adenoma (PA) tumors (42 of 99, 95% confidence interval 32.5–52.8%) demonstrated ≥20% of cells displaying the SSTR2 as compared to just 1% of all other tumors (1/160, 95% CI 0.02–3.4%). The other tumor was a neuroendocrine carcinoma. PA had a higher intensity of SSTR2 staining, with 90.9% staining ≥ an intensity of 2 (moderate). Tumors with an intensity of SSTR2 expression equal to or greater than 2 had an 89.9% likelihood of being a PA (95% CI: 82.2–95.0%, AUC: 0.928). Only one Warthin tumor demonstrated a 'strong' SSTR2 staining intensity. No Warthin tumor showed a percentage of cells staining for SSTR2 above ≥20%. This result demonstrates consistent and strong expression of SSTR2 in PAs as compared to Warthin tumors, which may allow physicians to utilize radioligand-somatostatin analog PET CT/MR imaging to diagnose the PA. SSTR2 positivity, if shown to be clinically relevant, may allow peptide receptor radionuclide therapy in the future. [ABSTRACT FROM AUTHOR]

Pooneh Kia,1 Umme Ruman,2 Ariyati Retno Pratiwi,3 Mohd Zobir Hussein2 1Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Nanomaterials Synthesis and Characterization Laboratory (NSCL), Institute of Nanoscience and Nanotechnology (ION2), Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia; 3Department of Oral Biology, Faculty of Dentistry, Universitas Brawijaya, Malang, IndonesiaCorrespondence: Mohd Zobir Hussein, Email mzobir@upm.edu.myAbstract: Tuberculosis (TB), derived from bacterium named Mycobacterium tuberculosis, has become one of the worst infectious and contagious illnesses in the world after HIV/AIDS. Long-term therapy, a high pill burden, lack of compliance, and strict management regimens are disadvantages which resulted in the extensively drug-resistant (XDR) along with multidrug-resistant (MDR) in the treatment of TB. One of the main thrust areas for the current scenario is the development of innovative intervention tools for early diagnosis and therapeutics towards Mycobacterium tuberculosis (MTB). This review discusses various nanotherapeutic agents that have been developed for MTB diagnostics, anti-TB drugs and vaccine. Undoubtedly, the concept of employing nanoparticles (NPs) has strong potential in this therapy and offers impressive outcomes to conquer the disease. Nanocarriers with different types were designed for drug delivery applications via various administration methods. Controlling and maintaining the drug release might be an example of the benefits of utilizing a drug-loaded NP in TB therapy over conventional drug therapy. Furthermore, the drug-encapsulated NP is able to lessen dosage regimen and can resolve the problems of insufficient compliance. Over the past decade, NPs were developed in both diagnostic and therapeutic methods, while on the other hand, the therapeutic system has increased. These “theranostic” NPs were designed for nuclear imaging, optical imaging, ultrasound, imaging with magnetic resonance and the computed tomography, which includes both single-photon computed tomography and positron emission tomography. More specifically, the current manuscript focuses on the status of therapeutic and diagnostic approaches in the treatment of TB.Keywords: tuberculosis, nanomedicine, theranostic, diagnostic, therapeutic

Mesenchymal stem cells (MSCs) transplantation is a promising approach for pulmonary fibrosis (PF), however it is impeded by several persistent challenges, including the lack of long-term tracking, low retention, and poor survival of MSCs, as well as the low labeling efficiency of nanoprobes. Herein, a cobalt protoporphyrin IX (CoPP) aggregation-induced strategy is applied to develop a multifunctional nano-self-assembly (ASCP) by combining gold nanoparticle (AuNPs), superparamagnetic iron oxide nanoparticles (SPIONs), and CoPP through a facile solvent evaporation-driven approach. Since no additional carrier materials are employed during the synthesis, high loading efficiency of active ingredients and excellent biocompatibility are achieved. Additionally, facile modification of the ASCPs with bicyclo[6.1.0]nonyne (BCN) groups (named as ASCP-BCN) enables them to effectively label MSCs through bioorthogonal chemistry. The obtained ASCP-BCN could not only help to track MSCs with AuNP-based computed tomography (CT) imaging, but also achieve an SPIONs-assisted magnetic field based improvement in the MSCs retention in lungs as well as promoted the survival of MSCs via the sustained release of CoPP. The in vivo results demonstrated that the labeled MSCs improved the lung functions and alleviated the fibrosis symptoms in a bleomycin–induced PF mouse model. Collectively, a novel ASCP-BCN multifunctional nanoagent was developed to bioorthogonally-label MSCs with a high efficiency, presenting a promising potential in the high-efficient MSC therapy for PF.