Search Results (134)

Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [¹⁷⁷Lu]Lu-PSMA-617 (¹⁷⁷Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; data from three parts are presented here. Part 1 evaluated safety and tolerability; Parts 2 (post-taxane) and 3 (pre-taxane/taxane-naive) assessed the overall response rate (ORR; primary endpoint), overall survival (OS), radiographic progression-free survival (rPFS), disease control rate (DCR), PFS, and safety; and Part 4 is the expansion part. Patients received 7.4 GBq (±10%) ¹⁷⁷Lu-PSMA-617 Q6W for up to six cycles. Results: Of the 35 patients who underwent a [⁶⁸Ga]Ga-PSMA-11 (⁶⁸Ga-PSMA-11) PET/CT scan, 30 received ¹⁷⁷Lu-PSMA-617 (post-taxane, n = 12; pre-taxane, n = 18). No dose-limiting toxicity was noted in Part 1 (n = 3). Post- and pre-taxane patients had a median of three and five cycles, respectively. The primary endpoint, ORR, met the pre-specified threshold, with the lower limit of the 90% confidence interval (CI) above the threshold of 5% for post-taxane and 12% for pre-taxane. Post- and pre-taxane patients had an ORR of 25.0% (90% CI: 7.2–52.7) and 33.3% (90% CI: 15.6–55.4), respectively. In post- and pre-taxane patients, the DCR was 91.7% and 83.3%, the median rPFS was 3.71 and 12.25 months, and the median PFS was 3.71 and 5.59 months, respectively. The median OS was 14.42 and 12.94 months in post- and pre-taxane patients, respectively. The most common adverse events were constipation, decreased appetite, decreased platelet count, anemia, and nausea. Conclusions: The primary endpoint (ORR) was met. The safety profile of ¹⁷⁷Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC. Full article

Background/Objectives: Red bone marrow irradiation is a major concern for patients with advanced prostate cancer undergoing [¹⁷⁷Lu]Lu-PSMA therapy. However, low uptake in the red bone marrow and the presence of bone lesions complicate image-based red bone marrow dosimetry. This study aimed to investigate the general feasibility of image-based red bone marrow activity estimation for [¹⁷⁷Lu]Lu-PSMA treatment and to develop a fully automated workflow for clinical implementation. Methods: In the first part of the study, 175 virtual patient phantoms with realistic ¹⁷⁷Lu activity distributions were generated based on 639 pre-therapeutic [¹⁸F]F-PSMA-1007 PET/CT scans. The SIMIND Monte Carlo tool was used to simulate the ¹⁷⁷Lu SPECT acquisitions (24 h post-injection (p.i.)), which were used to assess the uncertainty of red bone marrow activity estimation. In the second part, red bone marrow self- and cross-absorbed doses were estimated for four therapy cycles of 20 patients. Results: The simulation study shows a significant overestimation of activity in skeletal sites with bone lesions, with median recovery coefficients (RCs) across all phantoms yielding a median of 225% (range: 106–1015%). In contrast, the median RCs were markedly lower in skeletal sites neighboring or distant to lesion-carrying sites (105% [72–163%] and 107% [77–130%], respectively). The median total absorbed dose to the red bone marrow was 20.8 mGy/GBq (range: 5.6–297.9 mGy/GBq). Median blood levels decreased with an increasing median cumulative total absorbed dose. Conclusions: Reliable estimation of activity concentration in skeletal sites without bone lesion infiltration has been shown to be feasible. Based on this finding, an automated workflow for routine image-based red bone marrow dosimetry was developed. Full article

Prostate cancer is the second leading cause of cancer-related death in men, with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases representing a critical clinical challenge. Although radium-223 (Ra-223) is approved for treating mCRPC with bone metastases, its efficacy remains limited, necessitating the development of more effective therapies. This study investigates the therapeutic potential of ¹⁷⁷Lu-PSMA-617, a PSMA-targeted radiopharmaceutical, in a murine model of prostate cancer bone metastases. To our knowledge, this is the first study to systematically evaluate ¹⁷⁷Lu-PSMA-617 in an orthotopic bone metastatic prostate cancer model, providing a clinically relevant preclinical platform to assess both imaging and therapeutic performance. We conducted comprehensive preclinical evaluations, including synthesis, stability analysis, cell binding assays, nuclear imaging, in vivo biodistribution, pharmacokinetics, and antitumor efficacy. The synthesis of ¹⁷⁷Lu-PSMA-617 demonstrated high radiochemical yield (99.2%), molar activity (25.5 GBq/μmol), and purity (>98%), indicating high product quality. Stability studies confirmed minimal release of free Lutetium-177, maintaining the compound’s integrity under physiological conditions. In vitro assays showed selective binding and internalization in PSMA-positive LNCaP prostate cancer cells, with negligible uptake in PSMA-negative PC-3 cells. In vivo biodistribution studies demonstrated efficient tumor targeting, with peak uptake in LNCaP tumors (23.31 ± 0.94 %IA/g) at 4 h post-injection. The radiopharmaceutical exhibited favorable pharmacokinetics, with high tumor-to-background ratios (tumor-to-blood, 434.4; tumor-to-muscle, 857.4). Therapeutic efficacy was confirmed by significant survival extension in treated mice (30.7% for 37 MBq and 53.8% for 111 MBq), with median survival times of 34 and 40 days, respectively, compared to 26 days in the control group. Radiation dosimetry analysis indicated a favorable safety profile with a calculated effective dose of 0.127 mSv/MBq. These findings highlight the novelty and translational relevance of using ¹⁷⁷Lu-PSMA-617 in a clinically relevant bone metastasis model, reinforcing its potential as a dual-purpose agent for both targeted therapy and molecular imaging in advanced prostate cancer. Full article

Background: The ⁸⁹Zr radioisotope is increasingly vital in positron emission tomography (PET), especially immuno-PET, due to its long half-life of 78.4 h, allowing extended tracking of biological processes. This makes it particularly suitable for researching medicines with slow pharmacokinetics and enhances the precision of molecular imaging, especially in oncology. Despite zirconium’s potential for skeletal accumulation, effective chelation with agents like deferoxamine (DFO) enables high-resolution imaging of antigen-specific tumours, such as HER2-positive breast cancer, offering insights into tumour biology and treatment response. Methods: ⁸⁹Zr was produced at the ACSI TR-19 cyclotron via ⁸⁹Y(p,n)⁸⁹Zr reaction. Natural yttrium foils (250 μm) were irradiated with 12.9 MeV protons on target, with 100 μA·h. An HER2-targeting affibody was synthesized and conjugated with p-NCS-Bz-DFO (1:4 mass ratio) at 37 °C for 60 min (pH 9.2 ± 0.2), then purified on a PD-10 column. Radiolabelling was performed with [⁸⁹Zr]Zr-oxalate at pH ranging from 7.0 to 9.0, with concentrations from 110 to 460 MBq/mL. Results: Final activity reached 2.95 ± 0.31 GBq/batch (EOB corrected), with ≥ 99.9% radionuclide and ≥95% radiochemical purities. The anti-HER2 affibody was successfully radiolabelled with ⁸⁹Zr, resulting in a radiochemical purity of over 85% with molar activity of 26.5 ± 4.4 and 11.45 MBq/nmol at pH 7.0–7.5. In vitro tests on BT-474 and MCF-7 cell lines confirmed high uptake in HER2-positive cells, validating specificity and stability. Conclusions: The successful synthesis and labelling of the [⁸⁹Zr]Zr-p-NCS-Bz-DFO-anti-HER2 affibody are promising achievements for its further application in targeted immuno-PET imaging for HER2-positive malignancies. Further in vivo studies are needed to support its clinical translation. Full article

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a rising threat for immunocompromised cancer patients. The reduced immune defense may be a result of the malignancy itself or a side effect of therapy. While many chemotherapies can severely diminish the effect of vaccines against SARS-CoV-2, the effect of radioligand therapy has not yet been studied so far. Methods: In our database, 64 patient records of patients with metastatic castration-resistant prostate cancer that were treated with PSMA-directed radioligand therapy (PRLT) were randomly selected and checked for specific information (vaccination status, past corona virus disease 2019 (COVID-19) infections, the period between PRLT and vaccination, and antibody titers). A total of 30 patient records had sufficient information to examine the interference between PRLT and the vaccination against SARS-CoV-2. Results: In the analyzed cohort, 96.7% of the patients achieved seroconversion after receiving—on average—the third (booster) vaccination against SARS-CoV-2 and two PRLT cycles with average administered activities of 16.1 ± 7.2 GBq (435.1 ± 194.6 mCi) of lutetium-177 and 13.7 ± 6.6 MBq (0.37 ± 0.18 mCi) of actinium-225 (as part of ‘TANDEM therapies’) per patient. Conclusions: In the reviewed population, neither the initial response nor the maintenance of a positive immune response against the SARS-CoV-2 virus was undesirably affected by PRLT. The seroconversion rate and the absolute immune titers (in many cases >25,000 BAU/mL) are comparable to the normal population. This result implies the clinically important conclusion that neither an initial nor a booster vaccination against COVID-19 must be postponed if a PRLT is planned (and vice versa). Full article

Objective: Current good manufacturing practice (cGMP) guidance for positron emission tomography (PET) drugs has been established in Europe and the United States. In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) approved the use of radiosynthesizers as medical devices for the in-house manufacturing of PET drugs in hospitals and clinics, regardless of the cGMP environment. Without adequate facilities, equipment, and personnel required by cGMP regulations, the quality assurance (QA) and clinical effectiveness of PET drugs largely depend on the radiosynthesizers themselves. To bridge the gap between radiochemistry standardization and site qualification, the Japanese Society of Nuclear Medicine (JSNM) has issued guidance for the in-house manufacturing of small-scale PET drugs under academic GMP (a-GMP) environments. The goals of cGMP and a-GMP are different: cGMP focuses on process optimization, certification, and commercialization, while a-GMP facilitates the small-scale, in-house production of PET drugs for clinical trials and patient-specific standard of care. Among PET isotopes, N-13 has a short half-life (10 min) and must be synthesized on site. [¹³N]Ammonia ([¹³N]NH₃) is used for myocardial perfusion imaging under the Japan Health Insurance System (JHIS) and was thus selected as a working example for the manufacturing of PET drugs in an a-GMP environment. Methods: A [¹³N]NH₃-radiosynthesizer was installed in a hot cell within an a-GMP-compliant radiopharmacy unit. To comply with a-GMP regulations, the air flow was adjusted through HEPA filters. All cabinets and cells were disinfected to ensure sterility once a month. Standard operating procedures (SOPs) were applied, including analytical methods. Batch records, QA data, and radiation exposure to staff in the synthesis of [¹³N]NH₃ were measured and documented. Results: 2.52 GBq of [¹³N]NH₃ end-of-synthesis (EOS) was obtained in an average of 13.5 min in 15 production runs. The radiochemical purity was more than 99%. Exposure doses were 11 µSv for one production run and 22 µSv for two production runs. The pre-irradiation background dose rate was 0.12 µSv/h. After irradiation, the exposed dosage in the front of the hot cell was 0.15 µSv/h. The leakage dosage measured at the bench was 0.16 µSv/h. The exposure and leakage dosages in the manufacturing of [¹³N]NH₃ were similar to the background level as measured by radiation monitoring systems in an a-GMP environments. All QAs, environmental data, bacteria assays, and particulates met a-GMP compliance standards. Conclusions: In-house a-GMP environments require dedicated radiosynthesizers, documentation for batch records, validation schedules, radiation protection monitoring, air and particulate systems, and accountable personnel. In this study, the in-house manufacturing of [¹³N]NH₃ under a-GMP conditions was successfully demonstrated. These findings support the international harmonization of small-scale PET drug manufacturing in hospitals and clinics for future multi-center clinical trials and the development of a standard of care. Full article

Background: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (⁹⁰Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT). Methods: Contrast-enhanced T1-weighted magnetic resonance imaging (T1W-MRI) was used to delineate the tumor volumes and CT scans were used to automatically segment the organs at risk in nine patients with recurrent GBM. Volumetric Modulated Arc Therapy (VMAT) treatment plans were generated using a clinical treatment planning system. Assuming the relative intensity of each voxel from the MR-T1W as a valid surrogate for the post-IACI ⁹⁰Y-PVA-MB distribution, a specific ⁹⁰Y dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in a ⁹⁰Y-PVA-MB-based dose distribution that was then compared with the VMAT plans. Results: The physical dose distribution obtained from the simulation of 1GBq of ⁹⁰Y-PVA-MBs was rescaled to ensure that 95% of the prescribed dose was delivered to 95% or 99% of the target (i.e., A95% and A99%, respectively). The calculated activities were A95% = 269.2 [63.6–2334.1] MBq and A99% = 370.6 [93.8–3315.2] MBq, while the mean doses to the target were 58.2 [58.0–60.0] Gy for VMAT, and 123.1 [106.9–153.9] Gy and 170.1 [145.9–223.8] Gy for A95% and A99%, respectively. Additionally, non-target brain tissue was spared in the ⁹⁰Y-PVA-MB treatment compared to the VMAT approach, with a median [range] of mean doses of 12.5 [12.0–23.0] Gy for VMAT, and 0.6 [0.2–1.0] Gy and 0.9 [0.3–1.5] Gy for the ⁹⁰Y treatments assuming A95% and A99%, respectively. Conclusions: ⁹⁰Y-PVA-MB IACI using MR-T1W appears to be feasible and safe, as it enables the delivery of higher doses to tumors and lower doses to non-target volumes compared to the VMAT approach. Full article

The multi-model ensemble (MME) approaches are highly regarded in climate prediction and risk assessment for their capacity to integrate multiple global climate models (GCMs) and minimize uncertainties associated with individual models. However, the quantitative impacts of spatial scale, weighted ensemble, and bias correction on the spatiotemporal comprehensive performance of MME remain unknown. In this study, we comprehensively assessed the historical simulation capabilities of 41 CMIP6 GCMs at national, basin, and grid scales. Additionally, we investigated the impact of bias correction and weighted ensemble on enhancing climate simulation performance. The results indicate that CMIP6 models exhibit notable differences in simulating regional climate characteristics of China across different scales. Weighted multi-model ensemble schemes incorporating better-performing models consistently outperform equal-weight approaches, achieving an average 20.67% reduction in the DISO (distance between indices of simulation and observation) index, with temporal performance improvements being particularly pronounced. Bias correction played a critical role in the enhancement of MMEs, reducing DISO values by 41.60% on average, particularly in the spatial dimension. Among all MMEs, the grid-scale optimized ensemble (GBQ), combining bias correction, model selection, and performance-based weighting, demonstrated superior comprehensive performance, achieving the lowest DISO values across spatial and temporal dimensions. These findings provide new insights for enhancing regional climate simulation and evaluation, and they provide more reliable scientific information for investigating climate change and formulating adaptation strategies in China. Full article

Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that produce catecholamines. Unresectable or metastatic PPGLs are treated with [¹³¹I]metaiodobenzylguanidine (MIBG), but MIBG avidity is often heterogeneous. Identifying predictive factors for non-avid lesions on scintigraphy is clinically important. The primary objective of this study was to investigate the relationship between MIBG avidity and catecholamine secretion patterns in patients with unresectable or metastatic PPGLs. Methods: This retrospective study included 27 patients treated with [¹³¹I]MIBG for unresectable/metastatic PPGLs between 2001 and 2024. Patients received a single intravenous dose of [¹³¹I]MIBG (5.5–7.4 GBq), with post-therapy scintigraphy performed 3–7 days later. Non-avid lesions were assessed by imaging and confirmed using CT, MRI, and FDG-PET. Clinical factors, including age, sex, prior treatments, metastasis sites, and urine catecholamines, were evaluated using univariate logistic analysis. Predictive factors were assessed via receiver operating characteristic curves. Results: Non-avid lesions were found in nine patients (33.3%). These patients were younger (median age 38 vs. 62.5 years) and had higher urine dopamine levels (median 1510 vs. 779 μg/day) than those without non-avid lesions. Younger age (odds ratio: 0.892, p < 0.01) and higher urinary dopamine levels (odds ratio: 1.003, p < 0.01) were significantly associated with non-avid lesions. All patients > 45 years with urinary dopamine < 1190 μg/day had no non-avid lesions, whereas patients < 45 years with urinary dopamine > 1190 μg/day had non-avid lesions. Conclusions: Age and urinary dopamine levels may predict non-avid lesions in unresectable/metastatic PPGLs, aiding treatment decisions for [¹³¹I]MIBG therapy. This article is a revised and expanded version of a paper entitled “Urine dopamine level and age can predict non-avid lesion on scintigraphy after I-131 MIBG treatment for unresectable/metastatic PPGL”, which was presented at SNMMI 2024, Toronto, from 8 June to 11 June 2024. Full article

Background: The radiotracer [¹⁸F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an ¹⁸F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Although this procedure could be automated on two-reactor modules like the GE TRACERLab FX2N (FXN) to afford the tracer in modest radiochemical yields (RCY) of 18–25%, it is unsuitable for cassette-based systems with a single reactor. Methods: To simplify implementation on an automated synthesis module, the radiosynthesis of [¹⁸F]JK-PSMA-7 was devised as a one-pot, two-step reaction. The new method is based on direct (“late-stage”) radiofluorination of an appropriate onium triflate precursor and subsequent deprotection with ortho-phosphoric acid. It was successfully established on the cassette-based Trasis AllInOne (AIO) module. Results: Overall, the new protocol enabled the production of [¹⁸F]JK-PSMA-7 in activity yields of 39 ± 4% (RCY = 58%) with an overall synthesis time of about 1 h. In a single production run with an initial activity of 36-43 GBq, 13-19 GBq of [¹⁸F]JK-PSMA-7 with a radiochemical purity of >99% was obtained. Conclusions: We have established a highly reliable, GMP-compliant process for the automated radiosynthesis of [¹⁸F]JK-PSMA-7 on the Trasis AllinOne (AIO) synthesizer, ensuring consistent and efficient production of this radioligand. Full article

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/−T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of ¹³¹I exceeding 150 mCi (5.55 GBq) over approximately 53 months. Our results showed the following: (i) In DTC/−T2DM patients, high-cumulative ¹³¹I doses promote a pro-inflammatory state that accelerates the development of cardiotoxicity. Monitoring NT-proBNP, ST2/IL-33R, and cTn I in these patients may help identify those at risk of developing cardiac complications. (ii) In patients with DTC/+T2DM, high-cumulative ¹³¹I doses lead to the release of NT-proANP (r = 0.63), which signals that the atria are under significant stress. (iii) In patients with DTC/+T2DM, metformin suppresses inflammation, leading to a dose-dependent reduction in cTn I (r = −0.59). Monitoring cTn I and NT-proANP, and considering the use of metformin as part of the therapeutic strategy, could help manage cardiotoxicity in T2DM patients undergoing ¹³¹I therapy. Full article

Background: N-succinimidyl-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) is commonly prepared through a three-step procedure starting from [¹⁸F]fluoride ion. A number of methods for the single-step radiosynthesis of [¹⁸F]SFB have been introduced recently, including the radiofluorination of diaryliodonium salts and the Cu-mediated ¹⁸F-fluorination of pinacol aryl boronates and aryl tributyl stannanes, but they still have the drawbacks of lengthy product purification procedures. In the present work, two approaches for the direct labeling of [¹⁸F]SFB from diaryliodonium (DAI) salt (4) and pinacol aryl boronate (6) are evaluated, with a major focus on developing a fast and simple SPE-based purification procedure. Methods: DAI salt precursor 6 was labeled employing the common “minimalist” approach with a two-step reaction heating sequence. The Cu-mediated radiofluorination of 4 was accomplished using Bu₄NOTf as a phase transfer catalyst for the elution of [¹⁸F]fluoride, followed by radiofluorination in the same solvent. Several types of SPE cartridges were tested in the elution and SPE procedures. Results: The Cu-mediated ¹⁸F-fluorination of the pinacol aryl boronate precursor afforded a higher RCC of 56 ± 3% (n = 7), making it better suited for the one-pot synthesis of [¹⁸F]SFB. SPE-based purification was achieved using cation exchange and reverse-phase polymer resin cartridges, connected in series. In a full-batch test, [¹⁸F]SFB was obtained with an RCY of 30% (n. d. c.), RCP > 99%, A_m 96–155 GBq/µmol, and a synthesis time of ≤35 min. Conclusions: Compared to other published methods, [¹⁸F]SFB production via the Cu-mediated radiofluorination of pinacol aryl boronate precursor provides significant time and cost savings, coupled with an ease of implementation. Full article

Background: Neuroendocrine neoplasms (NENs) are neoplastic tumors developing in every part of the body, mainly in the gastrointestinal tract and pancreas. Their treatment involves the surgical removal of the tumor and its metastasis, long-acting somatostatin analogs, chemotherapy, targeted therapy, and radioligand therapy (RLT). Materials and Methods: A total of 127 patients with progressive neuroendocrine neoplasms underwent RLT—4 courses, administered every 10 weeks—with the use of 7.4 GBq [¹⁷⁷Lu]Lu-DOTA-TATE or tandem therapy with 1.85 GBq [¹⁷⁷Lu]Lu-DOTA-TATE and 1.85 GBq [⁹⁰Y]Y-DOTA-TATE. Assessment of short- and long-term complications, as well as the calculation of progression-free survival (PFS) and overall survival (OS) were performed. Results: RLT caused a statistically but not clinically significant decrease in blood morphology parameters during both short- and long-term observations. Glomerular filtration rate (GFR) significantly decreased only in a long-term observation after RLT; however, it was clinically acceptable. Computed predictions of progression-free survival (PFS) and overall survival (OS) indicated that five years post-RLT, there is a 74% chance of patients surviving, with only a 58.5% likelihood of disease progression. Conclusions: Computed predictions of PFS and OS confirmed treatment efficiency and good patient survival. RLT should be considered a safe and reliable line of treatment for patients with progressive NENs as it causes only a low number of low-grade adverse events. Full article

The radiometal gallium-68 (Ga-68) has garnered significant interest due to its convenient production via compact and widely available generators and the high performance of ⁶⁸Ga-labeled compounds for positron-emission tomography (PET) imaging for cancer diagnosis and management of patients undergoing targeted radionuclide therapy. Given the short half life of Ga-68 (68 min), microfluidic-based radiosynthesis is a promising avenue to establish very rapid, efficient, and routine radiolabeling with Ga-68; however, the typical elution volume of Ga-68 from a generator (4–10 mL) is incompatible with the microliter reaction volumes of microfluidic devices. To bridge this gap, we developed a microscale cartridge-based approach to concentrate Ga-68. By optimizing cartridge design, resin type, resin mass, and eluent composition, Ga-68 was reliably concentrated from ~6 mL to ~80 µL with high recovery efficiency (>97%, n = 14). Furthermore, this method is suitable for both single- and dual-generator setups. To demonstrate suitability of the concentrated radiometal for radiolabeling, we performed microdroplet synthesis of [⁶⁸Ga]Ga-PSMA-11, achieving high radiochemical yield (83 ± 11%, n = 3), excellent radiochemical purity (>99%), and high apparent specific activity (255–320 MBq/μg). The entire process, including Ga-68 concentration, radiosynthesis, purification, and formulation, was completed in 12 min. Starting with activity of 0.81–0.84 GBq, 0.51–0.64 GBq of product was produced, sufficient for multiple patient doses. This work paves the way to clinical-scale production of other ⁶⁸Ga-labeled compounds using droplet microreactor methods, or high-throughput labeling optimization or compound screening of ⁶⁸Ga-labeled probes using droplet reaction arrays. Full article

The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [¹⁷⁷Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, advanced, well-differentiated G1 and G2 in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) treated with [¹⁷⁷Lu]Lu-DOTA-TATE according to the decisions of a multidisciplinary team. All patients underwent four cycles of 7–8 GBq of [¹⁷⁷Lu]Lu-DOTA-TATE every 8 weeks. A whole-body scan (WBS) was performed 4, 48, and 168 h after each treatment. The dosimetry towards the organ at risk and target lesions was calculated. For each patient, renal and bone marrow parameters were evaluated before, during, and 3 months after the end of the treatment. Follow-up data were obtained and RECIST criteria were considered as the endpoint. Among 21 patients enrolled (mean age 65 ± 9 years); 17 (81%) were men and the small intestine was the most frequent location of disease (n = 12). A mild albeit significant variation (p < 0.05) in both platelets and white blood cell counts among all time points was observed, despite it disappearing 3 months after the end of the therapy. According to the RECIST criteria, 11 (55%) patients had a partial response to therapy and 8 (40%) had stable disease. Only one (5%) patient had disease progression 4 months after treatment. Our data confirm that [¹⁷⁷Lu]Lu-DOTA is safe and effective in controlling the burden disease of G1/G2 GEP-NETs patients. Full article