Current radiopharmaceuticals最新文献

Background and purpose: Radiopharmaceuticals are radioactive compounds used for diagnostic or therapeutic purposes which are most often administered intravenously. Adverse events that may induce both adverse reactions and drug-to-drug interactions with changes in expected biodistribution, potentially affecting patient safety and diagnostic accuracy. Adverse reactions are relatively rare due to the small doses and under-reporting is the norm. The aim of this study is to increase awareness of the need to report in order to create protocols for the management of such adverse events among professionals in a Nuclear Medicine Department.

Methods: A reporting system was established a decade ago through an electronic form to enhance adverse event registration. The radiopharmacist collects data for further communication with National Health authorities and develops an annual report with recommendations on the management of these adverse events.

Results: A total of 128 reports were collected, including 65 cases of extravasations, 18 adverse reactions, and 45 drug interactions. Over the years, reporting has been increasing, adverse reactions occurred at a higher incidence than reported in the literature, and each anomalous biodistribution was analysed for possible drug interaction. The annual reports have been used to develop a local guideline for the management of adverse reactions and recommendations for discontinuation of treatment to avoid interactions with radiopharmaceuticals.

Conclusion: The recognition of adverse events associated with radiopharmaceuticals is increasing, underlining the need for vigilant reporting and improved management strategies. An efficient reporting system promotes awareness of possible interactions between radiopharmaceuticals and other medicines and their potential adverse reactions to enhance patient safety.

Background: Evidence of inappropriate overuse and underuse of medical procedures has been documented in modern healthcare systems around the world. Excessive use of health services can contribute to a rapid increase in healthcare costs and harm the patient physically and psychologically; conversely, underuse can lead to the inability to provide effective treatments when clinically indicated.

Objective: The study's aim is twofold: a) to measure the appropriateness of PET prescription in a cohort of patients, offering empirical evidence of overuse of health care services; b) to evaluate how the overuse of PET could affect public health expenditure and, consequently, the system's financial sustainability.

Methods: In this observational study, we have analyzed prospectively and retrospectively health patient records who underwent 18F-FDG PET/TC scan at the Nuclear Medicine Department of the University Hospital Mater Domini in Catanzaro (Italy) from 29/09/2022 to 10/02/2023. Patients' diagnostic questions have been defined as appropriate, not completely appropriate and completely inappropriate according to the 18F-FDG PET/CT recommendations defined by the "Conditions of Supply and Indications of Prescriptive Appropriateness of Italian NHS (National Health Systems)" published in the Official Gazette no. 15 of 20 January 2016 (Decree 9 December 2015) and by the AIMN (Italian Association of Nuclear Medicine) guidelines.

Results: We gathered data from 500 oncological patients (242 males and 258 females). The results show that 423/500 of patients' prescriptions were appropriate, while 77/500 of patients' prescriptions were completely inappropriate (63/77) or not completely appropriate (14/77).

Conclusion: Analysis showed a not complete adherence to national guidelines and no shared decision-making approach.

Introduction: [⁶⁸Ga-DOTA-D-Phe1-Tyr3]octreotide ([⁶⁸Ga]Ga-DOTA-TOC) is a somatostatin analogue largely used in PET/CT applications for the detection of gastroenteropancreatic neuroendocrine tumors (GEP-NET). Initially, it was obtained using a ⁶⁸Ge/⁶⁸Ga generator. The increasing cost of good manufacturing practice-compliant generators has led to the need to find alternative ways of producing Gallium-68 (⁶⁸Ga). The aim of this work is to show the production optimization of [⁶⁸Ga]Ga-DOTA-TOC via cyclotron, derived from three years of experience.

Methods: The production of [⁶⁸Ga]GaCl₃ via the ⁶⁸Zn(p,n)⁶⁸Ga reaction was optimized using a PETtrace 800 cyclotron (equipped with ZnO liquid target) and the synthesis of [⁶⁸Ga]Ga- DOTA-TOC was performed by FASTlab2 developer system according to the Guidelines on Good Radiopharmacy Practice (cGRPP). Quality control process was validated according to the current specific monograph (2482) of the European Pharmacopoeia (Ph. Eur.).

Results: [⁶⁸Ga]Ga-DOTA-TOC was produced in 40 minutes; ten validation batches met the quality criteria expected by the Ph. Eur. The synthesis process has involved many issues due to the use of acidic reagents and related corrosion of some components of cyclotron and developer system, resulting in 12.2% failed syntheses and a target breakdown after 11 months.

Discussion: The main issues, their causes and the strategies used to solve them are reported in the troubleshooting section: thanks to these strategies, the number of failed syntheses has decreased, and today, we have achieved a 0% failure rate.

Conclusion: Liquid target production of [⁶⁸Ga]Ga-DOTA-TOC, once consolidated, instead of ⁶⁸Ge/⁶⁸Ga generator has many advantages.

Objectives: Zirconium-89 (⁸⁹Zr, t_1/2=3.27d) is an important β₊ emitting radionuclide used in Positron Emission Tomography (PET) immuno studies due to its unique characteristics and increased demand due to simple and cost-effective production capacity. Production of ⁸⁹Zr is achieved primarily through solid natural yttrium targets via different target preparation methodologies, such as electrodeposition, pressed foils, and spark plasma sintering. In this study, we have investigated the pressed solid target methodology.

Methods: The Yttrium Oxide (Y₂O₃) powder was pressed to pellet form and stacked over a different back support plate, such as platinum (Pt), niobium (Nb), and tantalum (Ta). The target was irradiated with approximately 12 MeV proton beam for 10-60 minutes at 20μA current. The irradiated target was purified through a solid phase extraction method via hydroxamate-based resin by manual or automatic approach. The purified ⁸⁹Zr was analyzed using gamma scintigraphy, and specific activity was calculated through Deferoxamine (DFO) chelation.

Results: ⁸⁹Zr radionuclide via pressed target was effectively produced with a production yield of 20-30 MBq/μA.h, and the purification was achieved in 35 minutes with (87.46)% average recovery and >98% purity while using automated purification, but manual purification took 2 hours with (91 ± 2)% recovery and >98% purity. The production yield was comparable to the reported pressed target approach. Deferoxamine chelation with ⁸⁹Zr-oxalate was performed with purity >98% and specific activity of 25-30 μCi/mmol.

Conclusion: In this study, we explored the production of ⁸⁹Zr by pressed targets and purification via manual or automated methods with good radionuclide purity. The chelation with DFO or its analog was performed with good labeling efficiency and stability.

Background: In this study, [⁶⁴Cu]Cu-NODAGA-RGD-BBN was prepared and its preclinical assessments were evaluated for PET imaging of GRPR overexpressing tumors.

Methods: NODAGA-RGD-BBN heterodimer peptide was successfully labeled with cyclotronproduced copper-64 at optimized conditions. The radiochemical purity of the radiotracer was checked by HPLC and RTLC methods. The stability of the radiolabeled compound was assessed in PBS (4°C) and in human blood serum (37°C). Binding affinity and internalization of [⁶⁴Cu]Cu-NODAGA-RGD-BBN were studied on PC3, LNCaP, and CHO cell lines. The biodistribution of the radiotracer was evaluated in normal and tumor-bearing mice.

Results: [⁶⁴Cu]Cu-NODAGA-RGD-BBN was prepared with radiochemical purity >99 ± 0.7% (HPLC/ITLC) and specific activity of 18.5 ± 2.2 TBq/mmol. The radiotracer showed high stability in PBS (95 ± 1.05%) and in human blood serum (96 ± 1.24%) and, high affinity to the GRP expressing tumor cells. [⁶⁴Cu]Cu-NODAGA-RGD-BBN showed hydrophilic (log p = -1.14) and agonistic nature. The biodistribution and imaging studies demonstrated high uptake at the tumor site at all intervals post-injection and 3-4 h post-injection can be considered an appropriate time of imaging.

Conclusion: The results indicated that [⁶⁴Cu]Cu-NODAGA-RGD-BBN radiolabeled heterodimer peptide can be considered as a high-potential agent for PET imaging of GRPRoverexpressing tumors.

Background: Radiation exposure poses a significant threat to reproductive health, particularly the male reproductive system. The testes, being highly sensitive to radiation, are susceptible to damage that can impair fertility and overall reproductive function. The study aims to investigate the radioprotective effects of apigenin on the testis through histopathological evaluation.

Materials and methods: This research involved utilizing a total of 40 mice, which were randomly divided into eight groups of five mice each. The groups were categorized as follows: A) negative control group, B, C, and D) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) respectively, E) irradiation group, and F, H, and I) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) in combination with irradiation. The irradiation procedure involved exposing the mice to a 2Gy X-ray throughout their entire bodies. Subsequently, histopathological assessments were conducted seven days after the irradiation process.

Results: The findings indicated that radiation exposure significantly impacted the spermatogenesis system. This research provides evidence that administering apigenin to mice before ionizing radiation effectively mitigated the harmful effects on the testes. Apigenin demonstrated radioprotective properties, positively influencing various parameters, including the spermatogenesis process and the presence of inflammatory cells within the tubular spaces.

Conclusion: Apigenin can provide effective protection for spermatogenesis, minimize the adverse effects of ionizing radiation, and safeguard normal tissues.

Aim: Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [¹¹C]PiB using commercially available dedicated [¹¹C]- Chemistry module from the synthesized precursor.

Background: [¹¹C]PiB is a promising radiotracer for PET imaging of β-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [¹¹C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [¹¹C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.

Methods: The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [¹¹C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [¹¹C]PiB with [¹¹C]CH₃OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life.

Results: The precursor for radiosynthesis of [¹¹C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [¹¹C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/μmol range.

Conclusion: A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [¹¹C]MeOTf as a methylating agent to synthesize [¹¹C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.

Purpose: This study aimed to evaluate the performance of 18F-MD-PSMA PET/CT in patients previously treated for prostate cancer by either surgery or therapy, but later relapsed biochemically.

Methods: This retrospective study enrolled 213 patients in sequence previously treated for prostate cancer by either surgery or therapy, but later PSA relapsed. A total of 191 of these 213 patients were included in this analysis. All patients were biochemically relapsed after radical prostatectomy or therapy, had 18F-MD-PSMA PET/CT scan within 1 week, and were off hormonal therapy at the time of the scans. The new tracer was compared directly with 11C-choline in sensitivity.

Results: In 3 patients, a side-by-side comparison between 18F-MD-PSMA and 11C-choline was performed, and it was found that the former was about 3 times more sensitive than the latter. The analysis of PET imaging using 18F-MD-PSMA in 191 relapsed patients showed that less than 10% of patients showed the disease limited in the prostate. Among the remote lesions, the number in decreasing order was bone, followed by lymph nodes and other organs. The maximal SUV in lesions in each patient followed an exponential decay, with SUV inclined to the lower end. The Gleason score measured at the diagnosis showed no correlation with the average number of lesions in each patient, the average maximal SUV values among this cohort of patients, and the PSA values measured at the time of PET imaging. The number of lesions observed in each patient has no correlation with the PSA value measured at the time of PET imaging. When PSA value was measured as an independent biomarker at the time of PET imaging, the positivity of PET imaging using 18F-MD-PSMA increased along with an increase in PSA value, but with exceptions where PSMA expression was low or negative. From the PET imaging of this radioligand, the majority of patients showed oligo-metastasis, favoring using local therapy to manage the disease.

Conclusion: An 18F-MD-PSMA as a radioligand was found to be superior to 11C-choline in the setting of patients with biochemical relapse after previous treatment. Its PET imaging results matched those of established PSMA radioligands, but its chemical structure was found to have added features to conjugate with other functional molecules, such as those with therapeutic properties. This radioligand lays the foundation for our further work.

Background: HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT.

Methods: Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used.

Results: 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04).

Conclusion: In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort.

Introduction: Arthritis is an inflammatory disorder that affects one or more joints of the body for various reasons, including autoimmune disorders, trauma, or infection. In many cases, traditional long-term treatment with various drug combinations (NSAIDs, diseasemodifying antirheumatic drugs, systemic corticosteroids, etc.) can provide relief, but many joints require additional local treatment. Radiosynovectomy (RSV) is an alternative method to current treatment options. Both the global supply shortage of ⁹⁰Y in recent years and the increasing use of ¹⁷⁷Lu-labeled radiopharmaceuticals in the field of nuclear medicine have made it possible to develop ¹⁷⁷Lu-labeled microparticles and test them in small groups as RSV agents. This study aimed to develop the ¹⁷⁷Lu labeled tin colloid formulation and demonstrate its invivo characterization.

Materials and methods: Particle size, shape, and labelling efficiency of the four formulations developed were determined. The formula with the highest labelling efficiency was selected for further studies. The quality of the formulation was evaluated based on radionuclidic, radiochemical, and microbial purity. In-vitro stability was evaluated by determining the labelling efficiency. In-vitro stability was tested in PBS and synovial fluid. The biological characterization was assessed using SPECT/CT after injecting the formulation into the normal knee joints of the rabbits.

Results: Aggregated colloidal particles were spherical with a particle size of <5 μm. Labelling efficiency and radiochemical purity were >95 and 97.65% (Rf=0.2), respectively. The formulation was stable in vitro for up to 72 hours, both in PBS and synovial fluid. The formulation was homogeneously distributed in the joint at 0 and 1 hour after injection, and radioactivity- related involvement and inguinal lymph node involvement due to possible leakage were not detected in the late period. No pyrogenic/allergic side effects were observed during this period.

Conclusion: ¹⁷⁷Lu-tin-colloid was successfully prepared under optimized reaction conditions with high binding efficiency and radiochemical purity. The radiolabeled colloid was found to be stable in-vitro both in PBS and synovial fluid at room temperature. Serial PCET/CT images revealed that the activity was completely retained within the synovial cavity, with no activity leakage out of the joint until 48 hours after the injection. With the support of the results from further clinical studies, it may be possible for the formulation to enter clinical use.