89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations.

BACKGROUND: The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. RESULTS: The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30-60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced high-contrast murine PET images at 1 h-5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. CONCLUSIONS: Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

BACKGROUND: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development. MAIN BODY: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals. CONCLUSION: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects.

The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection.

The International Atomic Energy Agency organized a technical meeting at its headquarters in Vienna, Austria, in 2022 that included 17 experts representing 12 countries, whose research spanned the development and use of radiolabeled agents for imaging infection. The meeting focused largely on bacterial pathogens. The group discussed and evaluated the advantages and disadvantages of several radiopharmaceuticals, as well as the science driving various imaging approaches. The main objective was to understand why few infection-targeted radiotracers are used in clinical practice despite the urgent need to better characterize bacterial infections. This article summarizes the resulting consensus, at least among the included scientists and countries, on the current status of radiopharmaceutical development for infection imaging. Also included are opinions and recommendations regarding current research standards in this area. This and future International Atomic Energy Agency-sponsored collaborations will advance the goal of providing the medical community with innovative, practical tools for the specific image-based diagnosis of infection.

Albumin-Binding and Conventional PSMA Ligands in Combination with 161Tb: Biodistribution, Dosimetry, and Preclinical Therapy.

The favorable decay characteristics of 161Tb attracted the interest of clinicians in using this novel radionuclide for radioligand therapy (RLT). 161Tb decays with a similar half-life to 177Lu, but beyond the emission of ß--particles and γ-rays, 161Tb also emits conversion and Auger electrons, which may be particularly effective to eliminate micrometastases. The aim of this study was to compare the dosimetry and therapeutic efficacy of 161Tb and 177Lu in tumor-bearing mice using SibuDAB and PSMA-I&T, which differ in their blood residence time and tumor uptake. Methods: [161Tb]Tb-SibuDAB and [161Tb]Tb-PSMA-I&T were evaluated in vitro and investigated in biodistribution, imaging, and therapy studies using PC-3 PIP tumor-bearing mice. The 177Lu-labeled counterparts served for dose calculations and comparison of therapeutic efficacy. The tolerability of RLT in mice was monitored on the basis of body mass, blood plasma parameters, blood cell counts, and the histology of relevant organs and tissues. Results: The prostate-specific membrane antigen (PSMA)-targeting radioligands, irrespective of whether labeled with 161Tb or 177Lu, showed similar in vitro data and comparable tissue distribution profiles. As a result of the albumin-binding properties, [161Tb]Tb/[177Lu]Lu-SibuDAB had an enhanced blood residence time and higher tumor uptake (62%-69% injected activity per gram at 24 h after injection) than [161Tb]Tb/[177Lu]Lu-PSMA-I&T (30%-35% injected activity per gram at 24 h after injection). [161Tb]Tb-SibuDAB inhibited tumor growth more effectively than [161Tb]Tb-PSMA-I&T, as can be ascribed to its 4-fold increased absorbed tumor dose. At any of the applied activities, the 161Tb-based radioligands were therapeutically more effective than their 177Lu-labeled counterparts, as agreed with the approximately 40% increased tumor dose of 161Tb compared with that of 177Lu. Under the given experimental conditions, no obvious adverse events were observed. Conclusion: The data of this study indicate the promising potential of 161Tb in combination with SibuDAB for RLT of prostate cancer. Future clinical studies using 161Tb-based RLT will shed light on a potential clinical benefit of 161Tb over 177Lu.

Recent Innovations and Nano-Delivery of Actinium-225: A Narrative Review.

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted.

Tachykinin Receptor-Selectivity of the Potential Glioblastoma-Targeted Therapy, DOTA-[Thi8,Met(O2)11]-Substance P.

Radiopharmaceutical development hinges on the affinity and selectivity of the biological component for the intended target. An analogue of the neuropeptide Substance P (SP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8,Met(O2)11]-SP (DOTA-[Thi8,Met(O2)11]SP), in the theranostic pair [68Ga]Ga-/ [213Bi]Bi-DOTA-[Thi8,Met(O2)11]SP has shown promising clinical results in the treatment of inoperable glioblastoma. As the theranostic targeting component, modifications to SP that affect the selectivity of the resulting analogue for the intended target (neurokinin-1 receptor [NK1R]) could be detrimental to its therapeutic potential. In addition to other closely related tachykinin receptors (neurokinin-2 receptor [NK2R] and neurokinin-3 receptor [NK3R]), SP can activate a mast cell expressed receptor Mas-related G protein-coupled receptor subtype 2 (MRGPRX2), which has been implicated in allergic-type reactions. Therefore, activation of these receptors by SP analogues has severe implications for their therapeutic potential. Here, the receptor selectivity of DOTA-[Thi8,Met(O2)11]SP was examined using inositol phosphate accumulation assay in HEK293-T cells expressing NK1R, NK2R, NK3R or MRGPRX2. DOTA-[Thi8,Met(O2)11]SP had similar efficacy and potency as native SP at NK1R, but displayed greater NK1R selectivity. DOTA-[Thi8,Met(O2)11]SP was unable to elicit significant activation of the other tachykinin receptors nor MRGPRX2 at high concentrations nor did it display antagonistic behaviour at these receptors. DOTA-[Thi8,Met(O2)11]SP, therefore has high potency and selectivity for NK1R, supporting its potential for targeted theranostic use in glioblastoma multiforme and other conditions characterised by NK1R overexpression.

Highly inert Cu(II) complexes of C-aryl bifunctional cyclam-picolinates with remarkable 64Cu-labelling and biodistribution.

Cyclam-picolinate chelators were functionalized via click chemistry with an additional carboxyl group for subsequent bioconjugation to antibodies or for the modification of the overall charge of the corresponding 64Cu-radiocomplexes. The C-aryl functionalization strategy developed here preserves the chemical properties of the radiocomplexes whilst deeply enhancing their applications within nuclear medicine.

The SARS-COV-2 Seroprevalence among Oncology Patients.

Patients with cancer are presumed to be vulnerable to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe clinical outcomes due to the immunocompromised state mediated by their underlying malignancies and therapy. The aim of this study was to estimate the SARS-CoV-2 seroprevalence, following second to fourth waves in solid tumour patients attending the Steve Biko Academic Hospital (SBAH) for diagnosis and treatment of cancer. We used the single-prick COVID-19 IgG/IgM Rapid Test Cassettes to detect SARS-CoV-2 IgG/IgM antibodies in 760 patients with solid tumours who were asymptomatic and who had never tested positive for coronavirus disease 2019 (COVID-19). Out of the 760 patients, 277 were male (36.4%), 483 were female (63.6%), and the mean age was 55 years (range 18−92). The estimated total seroprevalence was 33.2%. The seroprevalence status of the COVID-19 IgG/IgM antibodies rose significantly from the second wave (11.3%) to the third (67.38%) and then the fourth (69.81%) waves with roughly similar counts. A significant number of the seropositive patients were asymptomatic to COVID-19 (96%). There was a higher rate of seropositivity in cancer patients with hypertension (p < 0.05). Patients with breast, gynaecologic, and prostate cancers exhibited increased SARS-CoV-2 seropositivity. Although oncology patients may be susceptible to SARS-CoV-2 infection, our data indicate that these patients remained asymptomatic throughout various waves with an overall COVID-19 IgG/IgM antibody seropositivity of 33.16%, suggesting no risk of severe or fatal cases of COVID-19.

A decade of ubiquicidin development for PET imaging of infection: A systematic review.

BACKGROUND: Ubiquicidin is a peptide fragment with selective binding to negatively charged bacterial cell membranes. Besides its earlier labelling with gamma emitting radionuclides, it has been labelled with Positron Emission Tomography (PET) radionuclides in the last decade for imaging infection and distinguishing infectious disease from sterile inflammation. This systematic review aims to evaluate the technology readiness level of PET based ubiquicidin radiopharmaceuticals. METHODS: Two independent researchers reviewed all articles and abstracts pertaining ubiquicidin and PET imaging that are currently available. Scopus, Google Scholar and PubMed/Medline were used in the search. Upon completion of the literature search all articles and abstracts were evaluated and duplicates were excluded. All non-PET articles as well as review articles without new data were deemed ineligible. RESULTS: From a total of 17 papers and 10 abstracts the studies were grouped into development, preclinical and clinical studies. Development was published in 15/17 (88%) publications and 6/10 (60%) abstracts, preclinical applications in 9/17 (53%) publications and 1/10 (10%) of abstracts. Finally, clinical studies made up 6/17 (35%) of full publications and 4/10 (40%) of the available abstracts. Development results were the most abundant. All the findings in the different areas of development of ubiquicidin as PET radiopharmaceutical are summarized in this paper. CONCLUSION: Labelling procedures are generally uncomplicated and relatively fast and there are indications of adequate product stability. The production of PET radiopharmaceuticals based on UBI will therefore not be a barrier for clinical introduction of this technology. Systematization and unification of criteria for preclinical imaging and larger clinical trials are needed to ensure the translation of this radiopharmaceutical into the clinic. Therefore a conclusion with regards to the clinical relevance of ubiquicidin based PET is not yet possible.

Antibiotic-Derived Radiotracers for Positron Emission Tomography: Nuclear or "Unclear" Infection Imaging?

The excellent features of non-invasive molecular imaging, its progressive technology (real-time, whole-body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic-derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio-antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics.

Relevance of Palladium to Radiopharmaceutical Development Considering Enhanced Coordination Properties of TE1PA.

Invited for the cover of this issue are the group of Raphaël Tripier and Nathalie Le Bris at the University of Brest (UMR CNRS 6521 CEMCA; France), Cathryn H. S. Driver from the South African Nuclear Energy Corporation in Pretoria (South Africa), and their collaborators. The image depicts the beginning of a new area of research into palladium and complexation of its radioisotopes for applications in nuclear medicine. Read the full text of the article at 10.1002/chem.202200942.

Relevance of Palladium to Radiopharmaceutical Development Considering Enhanced Coordination Properties of TE1PA.

The limited use of palladium-103 and -109 radionuclides for molecular radiotherapy is surely due to the lack of appropriate ligands capable of fulfilling all criteria required for application in nuclear medicine. Furthermore, the thermodynamic properties of these complexes in solution remain difficult to establish. The challenge is compounded when considering that radiolabeling of compounds for translation to clinical trials requires fast complexation. Thus, the coordination of Pd(II) and 103/109 Pd-nuclides is a huge challenge in terms of molecular design and physicochemical characterization. Herein, we report a comprehensive study highlighting TE1PA, a monopicolinate cyclam - already established in nuclear imaging with 64 Cu-PET (positron emission tomography) imaging tracers - as a highly relevant chelator for natural Pd and subsequently 109 Pd-nuclide. The structural, thermodynamic, kinetic and radiolabeling studies of Pd(II) with TE1PA, as well as the comparison of this complex with three structurally related derivatives, support palladium-TE1PA radiopharmaceuticals as leading candidates for targeted nuclear medicine.

Precise activity measurements of medical radionuclides using an ionization chamber: a case study with Terbium-161.

BACKGROUND: 161Tb draws an increasing interest in nuclear medicine for therapeutic applications. More than 99% of the emitted gamma and X-rays of 161Tb have an energy below 100 keV. Consequently, precise activity measurement of 161Tb becomes inaccurate with radionuclide dose calibrators when using inappropriate containers or calibration factors to account for the attenuation of this low energy radiation. To evaluate the ionization chamber response, the sample activity must be well known. This can be performed using standards traceable to the Système International de Référence, which is briefly described as well as the method to standardize the radionuclides. METHODS: In this study, the response of an ionization chamber using different container types and volumes was assessed using 161Tb. The containers were filled with a standardized activity solution of 161Tb and measured with a dedicated ionization chamber, providing an accurate response. The results were compared with standardized solutions of high-energy gamma-emitting radionuclides such as 137Cs, 60Co, 133Ba and 57Co. RESULTS: For the glass vial type with an irregular glass thickness, the 161Tb measurements gave a deviation of 4.5% between two vials of the same type. The other glass vial types have a much more regular thickness and no discrepancy was observed in the response of the ionization chamber for these type of vials. Measurements with a plastic Eppendorf tube showed stable response, with greater sensitivity than the glass vials. CONCLUSION: Ionization chamber measurements for low-energy gamma emitters (< 100 keV), show deviation depending on the container type used. Therefore, a careful selection of the container type must be done for activity assessment of 161Tb using radionuclide dose calibrators. In conclusion, it was highlighted that appropriate calibration factors must be used for each container geometry when measuring 161Tb and, more generally, for low-energy gamma emitters.

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Combination of terbium-161 with somatostatin receptor antagonists-a potential paradigm shift for the treatment of neuroendocrine neoplasms.

PURPOSE: The ߯-emitting terbium-161 also emits conversion and Auger electrons, which are believed to be effective in killing single cancer cells. Terbium-161 was applied with somatostatin receptor (SSTR) agonists that localize in the cytoplasm (DOTATOC) and cellular nucleus (DOTATOC-NLS) or with a SSTR antagonist that localizes at the cell membrane (DOTA-LM3). The aim was to identify the most favorable peptide/terbium-161 combination for the treatment of neuroendocrine neoplasms (NENs). METHODS: The capability of the 161Tb- and 177Lu-labeled somatostatin (SST) analogues to reduce viability and survival of SSTR-positive AR42J tumor cells was investigated in vitro. The radiopeptides' tissue distribution profiles were assessed in tumor-bearing mice. The efficacy of terbium-161 compared to lutetium-177 was investigated in therapy studies in mice using DOTATOC or DOTA-LM3, respectively. RESULTS: In vitro, [161Tb]Tb-DOTA-LM3 was 102-fold more potent than [177Lu]Lu-DOTA-LM3; however, 161Tb-labeled DOTATOC and DOTATOC-NLS were only 4- to fivefold more effective inhibiting tumor cell viability than their 177Lu-labeled counterparts. This result was confirmed in vivo and demonstrated that [161Tb]Tb-DOTA-LM3 was significantly more effective in delaying tumor growth than [177Lu]Lu-DOTA-LM3, thereby, prolonging survival of the mice. A therapeutic advantage of terbium-161 over lutetium-177 was also manifest when applied with DOTATOC. Since the nuclear localizing sequence (NLS) compromised the in vivo tissue distribution of DOTATOC-NLS, it was not used for therapy. CONCLUSION: The use of membrane-localizing DOTA-LM3 was beneficial and profited from the short-ranged electrons emitted by terbium-161. Based on these preclinical data, [161Tb]Tb-DOTA-LM3 may outperform the clinically employed [177Lu]Lu-DOTATOC for the treatment of patients with NENs.

COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks.

The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID-19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation, and progression.

Towards Facile Radiolabeling and Preparation of Gallium-68-/Bismuth-213-DOTA-[Thi8, Met(O2)11]-Substance P for Future Clinical Application: First Experiences.

Substance P (SP) is a small peptide commonly known as a preferential endogenous ligand for the transmembrane neurokinin-1 receptor. Nuclear Medicine procedures currently involve radiolabeled SP derivatives in peptide radioligand endotherapy of inoperable glioblastoma. Promising clinical results sparked the demand for facile production strategies for a functionalized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[Thi8, Met(O2)11]-SP to allow for rapid Gallium-68 or Bismuth-213 complexation. Therefore, we provide a simple kit-like radiotracer preparation method that caters for the gallium-68 activity eluted from a SnO2 generator matrix as well as preliminary results on the adaptability to produce [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP from the same vials containing the same starting material. Following a phase of radioanalysis for complexation of gallium-68 to DOTA-[Thi8, Met(O2)11]SP and assessing the radiolabeling parameters, the vials containing appropriate kit-prototype material were produced in freeze-dried batches. The facile radiolabeling performance was tested and parameters for future human application were calculated to meet the criteria for theranostic loco-regional co-administration of activity doses comprising [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP mixed with [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP. [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP was prepared quantitatively from lyophilized starting material within 25 min providing the required molar activity (18 ± 4 GBq/µmol) and activity concentration (98 ± 24 MBq/mL), radiochemical purity (>95%) and sustained radiolabeling performance (4 months at >95% LE) as well as acceptable product quality (>95% for 120 min). Additionally, vials of the same starting materials were successfully adapted to a labeling strategy available for preparation of [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP providing sufficient activity for 1-2 human doses. The resultant formulation of [68Ga]Ga-/[213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP activity doses was considered of adequate radiochemical quality for administration. This investigation proposes a simple kit-like formulation of DOTA-[Thi8, Met(O2)11]SP-a first-line investigation into a user friendly, straightforward tracer preparation that would warrant efficient clinical investigations in the future. Quantitative radiolabeling was accomplished for [68Ga]Ga-DOTA-[Thi8, Met(O2)11]SP and [213Bi]Bi-DOTA-[Thi8, Met(O2)11]SP preparations; a key requirement when addressing the specific route of catheter-assisted co-injection directly into the intratumoral cavities.

Preclinical Assessment Addressing Intravenous Administration of a [68Ga]Ga-PSMA-617 Microemulsion: Acute In Vivo Toxicity, Tolerability, PET Imaging, and Biodistribution.

It has been herein presented that a microemulsion, known to be an effective and safe drug delivery system following intravenous administration, can be loaded with traces of [68Ga]Ga-PSMA-617 without losing its properties or causing toxicity. Following tolerated IV injections the capability of the microemulsion in altering [68Ga]Ga-PSMA-617 distribution was presented at 120 min post injection based on its ex vivo biodistribution results.

Elucidating the effect of specific surface area on the gastrointestinal absorption of nanostructured calcium through Calcium-45 in vivo radiotracing.

Low dietary calcium intake and absorption may increase the risk of hypocalcaemia disease states. Reducing the particle size of calcium-containing powders and increasing the specific surface area (SSA), may have high oral calcium bioavailability. The absorption of a single dose of different sized calcium carbonate nanoparticles was traced in Sprague-Dawley rats with radioactive calcium-45 (half-life = 162.6 days, ß- endpoint = 258 keV; 100%). Four calcium carbonate formulations (calcium-45) were administered to Sprague-Dawley rodents (6 per treatment; n = 24). The groups were [45Ca]CaCO3 SSA 3 m2/g, [45Ca]CaCO3 36 m2/g, [45Ca]CaCO3 64 m2/g and a separate [45Ca]CaCO3 36 m2/g formulation produced by flame assisted pyrolysis. Blood and urine were sampled periodically, and organs collected and analysed after euthanasia. No changes in SSA or crystallinity were observed when powders before or after irradiation were compared. The [45Ca]CaCO3 64 m2/g formulation presented with higher levels in blood 2 h after administration and a higher liver and femur concentration. These findings suggest [45Ca]CaCO3 64 m2/g could lead to increased oral bioavailability.

Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach.

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.