Current radiopharmaceuticals最新文献

Clinical imaging equipment technological advancements offer insight into the evolution of mathematical techniques used to estimate parameters necessary to characterize the microvasculature and, thus, differentiate normal tissues from abnormal ones. These parameters are blood flow (F), capillary endothelial permeability surface area product (PS), vascular fraction (v_e), and extravascular extracellular space size (EES,v_e). There are a number of well-established approaches that exist in the literature; however, their analysis is restricted by complexity and is heavily influenced by noise. On the other hand, these characteristics can also be calculated using simpler and straightforward approaches such as Up-Slope Method (USM) and Graphical Analysis (GA). The review looks into the theoretical background and clinical uses of these methodologies, as well as the applicability of these techniques in various sections of the human body.

Background: Radiotherapy is used as one of the most effective regimens for cancer treatment, while radioresistance is a major drawback in cancer treatment.

Objectives: This study aimed to evaluate the sensitizing effect of olanzapine (OLA) with X-ray on glioblastoma (U-87 MG) cells death.

Methods: The synergistic killing effect of OLA with ionizing radiation (IR) on glioma was evaluated by colony formation assay. The generations of reactive oxygen species (ROS) and protein carbonyl (PC) as oxidized proteins were determined in OLA-treated and irradiated cells.

Results: Results of this study showed that OLA reduced the number of colonies in irradiated glioma cells.OLA elevated ROS and PC levels in irradiated cells. The synergistic killing effect of OLA with IR in U-87 MG cells was observed at concentrations of 1 μM and 20 μM of OLA. The maximum radiosensitizing effect of OLA was observed at a concentration of 20 μM.

Conclusion: The present study demonstrates that OLA has a radiosensitizing effect on cell death induced by IR in glioma cells.

Background: The synthesis of ²²⁵Actinium derivatives was afforded by using PSMA- 617, DOTATATE peptides, and EDTMP ligand. Detailed experiments, quality control (QC), and stability studies were also well described. The radiolabelling reactions were performed in mild conditions with desirable radiochemical yields and high radiochemical purities.

Methods: PSMA-617, DOTATATE were radiolabelled with ²²⁵Actinium in 0.1 M HCl in the presence of ascorbate buffer solution and passed through the C-18 light cartridge for purification and the product was eluted by ethanol-water solution. EDTMP was also radiolabelled with ²²⁵Actinium without using any stabilizer and purification step. All products were well analyzed by R-TLC and R-HPLC. The stability of those compounds was also studied within the validity period of time.

Results: ²²⁵Ac-DOTATATE and 225Ac-PSMA-617 were obtained at the same condition. The radiochemical yield of 225Ac-DOTATATE was less than²²⁵Ac-PSMA 617. The stability experiments indicating decay daughters of ²²⁵Actinium appeared after T0 +1 h due to the recoil effect radiolysis. On the other hand, ²²⁵Ac-EDTMP was more stable than DOTA-peptide radiolabelled compounds. ²²⁵Ac-EDTMP was produced with more than 95% radiochemical yield and 99% radiochemical purity.

Conclusion: A detailed chemistry study was presented for the synthesis of ²²⁵Actinium derivatives in mild conditions with absolute radiochemical purities and high yields. The experimental results showed that ²²⁵Ac-EDTMP could be a suitable radiopharmaceutical alternative for bone metastases arising from primer tumors as a cocktail therapy.

Background: 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO) when conjugated with a bifunctional chelator 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4- oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODAGA) (hereafter referred to as Cell Death Indicator [CDI]), enters dead and dying cells and binds to 90kDa heat shock proteins (hsp90).

Objective: This study assesses stability, biodistribution, imaging, and radiation dosimetry of [68Ga]- Ga-CDI for positron emission tomography (PET).

Methods: Preparation of [⁶⁸Ga]Ga-CDI was performed as previously described. Product stability and stability in plasma were assessed using high-performance liquid chromatography. Biodistribution and imaging were conducted in ten healthy male Lewis rats at 1 and 2 h following intravenous [⁶⁸Ga]Ga-CDI injection. Human radiation dosimetry was estimated by extrapolation for a standard reference man and calculated with OLINDA/EXM 1.1.

Results: Radiochemical purity of [⁶⁸Ga]Ga-CDI averaged 93.8% in the product and 86.7% in plasma at 4 h post-synthesis. The highest concentration of [⁶⁸Ga]Ga-CDI is observed in the kidneys; [⁶⁸Ga]Ga-CDI is excreted in the urine, and mean retained activity was 32.4% and 21.4% at 1 and 2 h post-injection. Lower concentrations of [⁶⁸Ga]Ga-CDI were present in the small bowel and liver. PET CT was concordant and additionally demonstrated focal growth plate uptake. The effective dose for [⁶⁸Ga]Ga-CDI is 2.16E-02 mSv/MBq, and the urinary bladder wall received the highest dose (1.65E-02 mSv/Mbq).

Conclusion: [⁶⁸Ga] Ga-CDI is stable and has favourable biodistribution, imaging, and radiation dosimetry for imaging of dead and dying cells. Human studies are underway.

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (⁹⁰Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach.

Methods: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50-fold excess of DOTA and then labelled with 90Y3+. The ⁹⁰Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the ⁹⁰Y-DOTA-nimotuzumab stability was evaluated in human plasma.

Results: The radioimmunoconjugate ⁹⁰Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma.

Conclusions: The optimized conditions for a mild and easy preparation of ⁹⁰Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for β- radio-guided surgery.

Background: Cancer is one of the diseases causing society's fears as a stigma of death and pain. Head and Neck Squamous Cell Carcinoma (HNSCC) is a group of malignant neoplasms of different locations in this region of the human body. It is one of the leading causes of morbidity and mortality in Brazil, because these malignant neoplasias, in most cases, are diagnosed in late phases. Surgical excision, chemotherapy and radiotherapy encompass the forefront of antineoplastic therapy; however, the numerous side effects associated with these therapeutic modalities are well known. Some treatments present enough potential to help or replace conventional treatments, such as Magnetic Hyperthermia and Photodynamic Therapy. Such approaches require the development of new materials at the nanoscale, able to carry out the loading of their active components while presenting characteristics of biocompatibility mandatory for biomedical applications.

Objective: This work aims to make a bibliographical review of HNSCC treatments. Recent techniques proven effective in other types of cancer were highlighted and raised discussion and reflections on current methods and possibilities of enhancing the treatment of HNSCC.

Methods: The study was based on bibliometric research between the years 2008 and 2019 using the following keywords: Cancer, Head and Neck Cancer, Chemotherapy, Radiotherapy, Photodynamic Therapy, and Hyperthermia.

Results: A total of 5.151.725 articles were found, 3.712.670 about cancer, 175.470 on Head and Neck Cancer, 398.736 on Radiotherapy, 760.497 on Chemotherapy, 53.830 on Hyperthermia, and 50.522 on Photodynamic Therapy.

Conclusion: The analysis shows that there is still much room for expanding research, especially for alternative therapies since most of the studies still focus on conventional treatments and on the quest to overcome their side effects. The scientific community needs to keep looking for more effective therapies generating fewer side effects for the patient. Currently, the so-called alternative therapies are being used in combination with the conventional ones, but the association of these new therapies shows great potential, in other types of cancer, to improve the treatment efficacy.

Background: An accurate measurement of the target volume is of primary importance in theragnostics of hyperthyroidism.

Objective: Our purpose was to evaluate the accuracy of a threshold-based isocontour extraction procedure for thyroid tissue volumetry from SPECT-CT.

Methods: Cylindrical vials with a fixed volume of 99mTcO4 at different activities were inserted into a neck phantom in two different thickness settings. Images were acquired by orienting the phantom in different positions, i.e., 40 planar images and 40 SPECT-CT. The fixed values of the isocontouring threshold for SPECT and SPECT-CT were calculated by means of linear and spline regression models. Mean, Median, Standard Deviation, Standard Error, Mean Absolute Percentage Error and Root Mean-Square Error were computed. Any difference between the planar method, SPECT and SPECT-CT and the effective volume was evaluated by means of ANOVA and posthoc tests. Moreover, planar and SPECT-CT acquisitions were performed in 8 patients with hyperthyroidism, considering relevant percentage differences greater than > 20% from the CT gold standard.

Results: Concerning phantom studies, the planar method shows higher values of each parameter than the other two methods. SPECT-CT shows lower variability. However, no significant differences were observed between SPECT and SPECT-CT measurements. In patients, relevant differences were found in 7 out of 9 lesions with the planar method, in 6 lesions with SPECT, but in only one with SPECT-CT.

Conclusion: Our study confirms the superiority of SPECT in volume measurement if compared with the planar method. A more accurate measurement can be obtained from SPECT-CT.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in β-cells, but it is highly expressed in human insulinomas and gastrinomas. Several GLP-1 receptor- avid radioligands have been developed to image insulin-secreting tumors or to provide a quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4 is a high affinity ligand of the GLP1- R, which is a candidate for being labeled with a PET isotope and used for imaging purposes.

Objective: Here, we report the development and validation results of a semi-manual procedure to label [Lys40,Nle14(Ahx-NODAGA)NH2]exendin-4, with Ga-68.

Methods: A⁶⁸Ge/⁶⁸Ga Generator (GalliaPharma®, Eckert and Ziegler) was eluted with 0.1M HCl on an automated synthesis module (Scintomics GRP®). The peptide contained in the kit vial (Radioisotope Center POLATOM) in different amounts (10-20-30 μg) was reconstituted with 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethansulfonic acid (HEPES) solution and ⁶⁸GaCl₃ (400-900 MBq), followed by 10 min incubation at 95°C. The reaction solution was then purified through an Oasis HLB column. The radiopharmaceutical product was tested for quality controls (CQs) in accordance with the European Pharmacopoeia standards.

Results: The synthesis of [⁶⁸Ga]Ga-NODAGA-Exendin-4 provided optimal results with 10 μg of peptide, getting the best radiochemical yield (23.53 ± 2.4%), molar activity (100 GBq/μmol) and radiochemical purity (91.69%).

Conclusion: The study developed an imaging tool [⁶⁸Ga]Ga-NODAGA-Exendin-4, avoiding pharmacological effects of exendin-4, for the clinical community.

Background: Fluorine-18 is one of the promising radiotracers that can report target specific information related to its physiology to understand the disease status through the PET modality. In the current study, the radiochemical synthesis, purification, and molecular docking studies of fluorine-18 (18F) radiolabeled coumarin-triazole hybrid have been performed.

Objective: To develop target specific fluorine-18 radiotracer for the diagnosis in oncology.

Methods: GE Tracer-lab FX2N module with few modifications in the line connections was used for the radiosynthesis and purification of target molecule [¹⁸F]SG-2, 4-((2,6-dimethylmorpholino) methyl)-7-((1-(4-(fluoro-¹⁸F) benzyl)-1H-1,2,3-triazol-4-yl) oxy)-2H-chromen-2-one, through the nucleophilic radiofluorination mechanism. The radiochemical purity was measured by HPLC, and TLC analytical methods. The kryptofix levels were also evaluated by using the TLC method. The residual solvents like DMF, ethanol were measured using GC. The Schrödinger drug discovery suite 2018 was used to study the protein and ligand interactions.

Results: The quality control parameters revealed the purity, chemical identity, and limits of residual solvents. The radiochemical purity was 95.5 ± 2.3%, and dimethylformamide solvent limit was 89 ± 3 ppm. The molecular docking results had suggested that the cold target molecule has made strong electronic interactions and showed the possible pharmacokinetic (ADME) properties with galectin-1 protein. Overall, these results showed that [[¹⁸F]SG-2 radiolabeling with 18F radionuclide was feasible, and support of molecular docking studies suggest possible interactions with Galectin- 1.

Conclusion: we reported a feasibility study for labeling coumarin-triazole hybrid with fluorine-18 through aromatic nucleophilic fluorination reaction (S_NAr).

Background: Peptide receptor radionuclide therapy (PRRT) has been recently approved for advanced, metastatic, or progressive neuroendocrine tumors (NETs).

Objective: This study reports the adverse events (AEs) observed with patient-tailored administered activity.

Methods: Fifty-two PRRT naive patients were treated with 177Lu-DOTATATE. The administered activity ranges between 2.78 and 5.55 GBq/cycle using the patient's unique characteristics (age, symptoms, blood work, and biomarkers).

Results: The protocol was well tolerated with the overwhelming majority of participants being forty- six (88%), completing all 4 induction therapy cycles. The median cumulative administered activity was 19.6 GBq (ranged 3.8-22.3 GBq). A total of 42/52 (81%) reported at least one symptom, and 43/52 (83%) had evidence of biochemical abnormality at enrollment that would meet grade 1 or 2 criteria for AEs. These symptoms only slightly increase with treatment to 50/52 (96%) and 51/52 (98%), respectively. The most common symptoms were mild fatigue (62%), shortness of breath (50%), nausea (44%), abdominal pain (38%), and musculoskeletal pain (37%). The most common biomarker abnormalities were mild anemia (81%), reduced estimated glomerular filtration rate (eGFR) (58%), increased alkaline phosphatase (ALP) (50%), and leukopenia (37%). Of critical importance, no 177Lu-DOTATATE related grade 3 or 4 AEs were observed.

Conclusion: Tailoring the administered activity of 177Lu-DOTATATE to the individual patient with a variety of NETs is both safe and well-tolerated. No patient developed severe grade 3 or 4 AEs. Most patients exhibit symptoms or biochemical abnormality before treatment and this only slightly worsens following induction therapy.