Antonino Sammartano

Background/Objectives: Fertility preservation (FP) has become an integral component of multidisciplinary care for patients at risk of treatment- or disease-related infertility. Although several established and emerging fertility preservation strategies are currently available, important challenges remain regarding patient selection, timing of intervention, long-term reproductive outcomes, and the translation of experimental approaches into routine clinical practice. This review critically appraises the current evidence on female and male fertility preservation, highlighting established techniques, emerging technologies, unresolved clinical challenges, and future research priorities. Oocyte vitrification remains the preferred strategy for postpubertal women when ovarian stimulation is feasible, whereas ovarian tissue cryopreservation has become an established option for selected patients requiring urgent treatment or for prepubertal girls. In men, sperm cryopreservation remains the standard of care, while fertility preservation in prepubertal boys is still investigational. Despite excellent laboratory outcomes, the real-world utilization of cryopreserved reproductive material remains unexpectedly low, highlighting persistent barriers in patient referral, counselling, and long-term follow-up. Methods: A structured narrative review was conducted using PubMed/MEDLINE and Embase to identify international guidelines, systematic reviews, meta-analyses, multicentre cohorts, registry-based studies, and original clinical investigations published between January 2015 and June 2025. Evidence was synthesized according to sex, age, fertility preservation indication, and clinical applicability. Interventions reviewed include oocyte and embryo cryopreservation, ovarian tissue cryopreservation (OTC), GnRH agonist co-treatment, ovarian transposition, in vitro maturation (IVM), sperm banking, surgical sperm retrieval (SSR), testicular tissue cryopreservation (TTC), and spermatogonial stem-cell (SSC) approaches. Results: Oocyte vitrification remains the preferred strategy for postpubertal women when ovarian stimulation is feasible, whereas ovarian tissue cryopreservation has become an established option for selected patients requiring urgent treatment or for prepubertal girls. In men, sperm cryopreservation prior to therapy is standard; SSR provides sperm for selected azoospermic cases. Paediatric FP strategies are asymmetric: OTC is clinically established, while TTC remains investigational. Random-start COS and aromatase inhibitor or tamoxifen protocols minimise treatment delay and hormonal exposure, and GnRHa co-treatment can serve as an adjunctive ovarian-protective measure. Despite high laboratory success, utilisation of banked gametes and tissue is modest, underscoring the need for structured referral pathways, patient counselling, and longitudinal follow-up. Conclusions: FP should be systematically integrated into both oncological and non-oncologic care pathways, with timely referral, age- and sex-specific counselling on live-birth probabilities, and long-term follow-up. Future priorities include harmonization of clinical protocols, standardized outcome reporting, registry-based long-term follow-up, and validation of emerging technologies to improve both reproductive outcomes and equitable access to fertility preservation.

Background/Objectives: Fertility preservation (FP) spans oncological and non‑oncological indications, including gonadotoxic therapies, benign haematological/metabolic disorders, conditions at risk of premature ovarian insufficiency, severe andrological disease, and elective plans to defer childbearing. We provide a sex‑integrated overview of established and emerging FP strategies and their real‑world effectiveness [1–10]. Methods: Narrative synthesis of guidelines and high‑quality studies (to 2025), prioritising ASCO/ESHRE guidance, systematic reviews, and multicentre/registry data covering oocyte/embryo cryopreservation, ovarian tissue cryopreservation (OTC), GnRH agonists, ovarian transposition, in vitro maturation (IVM), sperm banking, surgical sperm retrieval (SSR), testicular tissue cryopreservation (TTC), and spermatogonial stem‑cell (SSC) approaches [1–10]. Results: For women, oocyte vitrification is the first‑line option when time allows; OTC is established when stimulation is infeasible or in prepubertal girls, with endocrine recovery common and increasing pregnancy/live‑birth reports. For men, sperm cryopreservation before therapy is standard; SSR supports selected cases. Paediatric TTC is feasible but remains experimental, whereas paediatric OTC is clinically implemented. Random‑start COS and letrozole/tamoxifen protocols minimise treatment delay and hormonal exposure; GnRHa co‑treatment preserves ovarian function as an adjunct. Utilisation of banked gametes/tissue remains modest, underscoring the need for pathway optimisation [1–10]. Conclusions: FP should be embedded across oncology and non‑oncology pathways with timely referral, clear counselling on probabilities of live birth, and robust follow‑up. Standardisation, registry‑based evidence and long‑term offspring safety data are priorities to bridge the gap between laboratory potential and clinical effectiveness [1–10].

Background: high-sensitive cardiac TroponinI (hs-cTnI) is widely used for diagnosis of acute coronary syndromes. The latest recommendation for hs-cTnI determination is the protocol 0–1 h finalized to improve the rule out accuracy of the test. A Point of Care Testing able to guarantee these performances could be very useful due to reducing the turnaround time and ruling out patients suspected of ACS, especially by using biological matrices that are not required for centrifuge. The aim of our work is to compare the results for hs-cTnI obtained using different biological matrices and anticoagulants, obtained between Atellica^® VTLi hs-cTnI POCT and Access AccuTnI+3 DxI800 performances, in order to establish a possible bias derived directly from these pre-analytical conditions. Methods: Li-heparinized pool samples were primary employ for hs-cTnI with Atellica^® VTLi as whole blood, then centrifuged and tested on Atellica^® VTLi and DxI800. K₃EDTA pool samples were centrifuged and measured on DxI800 too. A comparison of methods was performed according to CLSI_EP-09A2 protocol. Constant and proportional errors were investigated with Deming regression. Bias between methods was evaluated with the Bland Altman test. Results: comparing whole blood lithium heparin results obtained with Atellica versus lithium heparin and K₃EDTA plasma tested on DxI 800, the Deming regression revealed a proportional error, whereas in both cases Bland Altman highlighted a minimal underestimation. A similar performance was revealed when considering plasma lithium heparin tested on Atellica versus lithium heparin and K₃EDTA plasma obtained with DxI800, confirming the same underestimation. Considering values close to the cut off, no significant differences were found. Conclusions: in the laboratory, the estimation of the bias of two different analyzers is pivotal. Once more this is crucial when different biological matrices and anticoagulants are employed for the analysis. Our study demonstrates that no significant differences among the two matrices are present when comparing Atellica and DxI800 performances.

Current data suggest little to no possibility of original COVID-19 transmission in pregnant women to the fetus during pregnancy or childbirth. Warning with Omicron new variants has decreased. A clinical case of a SARS-CoV-2 virus transplacental infection of a newborn, born at the end of 2022, from a mother who tested positive for Sars-covid-2 and positive IgM SARS-CoV-2 anti-virus. The newborn tested positive for SARS-CoV-2 12 hours after birth, and was clinically symptomatic after three days, an increase in IgM antibodies was not found, although the virus was identified in the urine samples through molecular tests. The insufficient time to determine the presence of antibodies and the immune system’s state of immaturity can explain the lack of IgM in the newborn’s blood at 14 days after birth. The Omicron SARS-CoV-2 keeps provoking infections among newborns, especially if the mother contracts it during the third trimester. The host response is most likely influenced by the newborn’s peculiar state of immune immaturity. Just before birth, a positive nasal swab and the presence of a positive urine examination confirmed the diagnosis of intraplacental exposure. Research on the virus through molecular tests of urines can represent an additional technique when an aetiological framework of the infection is necessary and a distinction between congenital and post-natal forms. (www.actabiomedica.it)

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: A ⁶⁸Ge/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: Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules. Methods: The aim of this study was to evaluate the annual performance of five consecutive ⁶⁸Ge/⁶⁸Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (⁶⁸Ga-DOTATOC, ⁶⁸Ga-PSMA-HBED-CC, ⁶⁸Ga-PENTIXAFOR and ⁶⁸Ga-DOTATATE). Results: The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for ⁶⁸Ga-DOTATOC, ⁶⁸Ga-PSMA-HBED-CC, ⁶⁸GaPENTIXAFOR and ⁶⁸Ga-DOTATATE. Conclusion: The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable ⁶⁸Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in β-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R–avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a ⁶⁸Ge/⁶⁸Ga Generator (GalliaPharma^®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP^®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 μg/mL) and [⁶⁸Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [⁶⁸Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5–0.75 μg/mL for both the analytes (NODAGA-exendin-4 and ⁶⁸Ga-NODAGA-exendin-4), with a correlation coefficient (R²) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [⁶⁸Ga]Ga-NODAGA-exendin-4 was linear with a R² of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 μg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [⁶⁸Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Introduction: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. Methods: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: ¹⁸F-FDG, ¹⁸F-choline (FCH), and ⁶⁸Ga-PSMA. Results: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue ¹⁸F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). Conclusions: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2–positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.

Purpose of the Study: Gallium (Ga)-68-DOTA peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumor imaging using positron emission tomography. However, at the moment, a specific monograph in the European Pharmacopoeia (Ph. Eur.) does exist only for Ga-68-edotreotide (DOTATOC) injection. Here, we report on the validation process of Ga-68-DOTA-Tyr3-octreotate (DOTATATE) cassette-based production and quality control (QC). Materials and Methods: Preparation of Ga-68-DOTATATE was performed according to the current European Union-good manufacturing practices, the current good radiopharmacy practice, the Ph. Eur., and the guidelines on validation of analytical methods for radiopharmaceuticals. Process was validated via three consecutive production runs to ensure that the methods are reproducible and reliable in routine use. The QC tests for Ga-68-DOTATATE were radiochemical purity (RCP – high-pressure liquid chromatography [HPLC]), radiochemical impurities ⁶⁸Ga³⁺ (HPLC and instant thin layer chromatography [ITLC]), chemical purity (HPLC and gas chromatography [GC]), pH (pH-strips), radionuclidic purity (principal γ-photon), germanium-breakthrough (⁶⁸Ge-content), Ga-68 half-life (γ-ray spectrometry), and sterility/endotoxin assay. Results: Radiolabeling procedure of Ga-68-DOTATATE fits all the applicable Ph. Eur. specifications. RCP measured via ITLC was >99% in the three validation batches. HPLC-measured RCP resulted 99.45%, 99.78%, and 99.75%. Germanium-breakthrough was far below the recommended level established in the Ph. Eur. Ga-68-DOTATOC injection (#2482). Residual ethanol tested with GC was less than 10%. All the batches were tested for endotoxin content, which always resulted lower than 17.5 EU/ml. All preparations passed the sterility tests. pH of the final product was 7 in all samples. Conclusion: Ga-68-DOTATATE fulfilled all the pre-set QCs and release criteria in the batches considered for this validation study. The results demonstrated a batch-to-batch reproducibility, ensuring that synthesis process leads to the expected final product in terms of yield, quality, reliability, safety, and efficacy.