Current Radiopharmaceuticals - Volume 16, Issue 4, 2023

Background: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. Objective: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. Methods: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. Results: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. Conclusion: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

The use of the one-of-a-kind qualities possessed by substances at the nanoscale is the core concept of nanotechnology. Nanotechnology has become increasingly popular in various business sectors because it enables better construction and more advanced product design. Nanomedicine is the name given to the application of nanotechnology in the medical and healthcare fields. It has been used to fight against some of the most prevalent diseases, such as cancer and cardiovascular diseases. This current manuscript provides an overview of the recent advancements in nanotechnology in drug delivery and imaging.

Background: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. Objective: The aim of this study was to associate BSI with OS in bone metastatic BC patients. Methods: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. Results: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). Conclusion: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Background: During the development of novel Re-188 radiopharmaceuticals, it was discovered that no calibration settings were published to calibrate Re-188 on the Capintec CRC-25PET dose calibrator. Methods: Sodium [¹⁸⁸Re]perrhenate was eluted from an OncoBeta ¹⁸⁸W/¹⁸⁸Re generator to measure activity on a Capintec CRC-25R dose calibrator using established dose calibrator settings provided by the manufacturer. The eluent was then used to tune the calibra on settings on a Capintec CRC-25PET dose calibrator, accounting for geometry. Radionuclidic purity of the [¹⁸⁸Re]perrhenate source was verified via gamma spectroscopy. Results: The calibrator number for Re-188 was determined to be 469 x 10 for the Capintec CRC-25PET dose calibrator, which differed from the manufacturer provided calibra on number of 496 x 10 for the Capintec CRC-25R dose calibra on model. W-188 breakthrough was characterised as < 0.01%. Conclusion: This previously unreported calibration number can be used to determine the activity of Re- 188 labelled radiopharmaceuticals using the Capintec CRC-25PET dose calibrator model.

Introduction: Hypoxia imaging agents can selectively remain in hypoxic tissue, which can directly reflect the location and degree of hypoxia. Methods: Synthesized a novel tumor hypoxia imaging probe [^99mTc]Tc(CO)3-CPA-2-NIM and evaluated its biological behavior with the purpose to assess its possibility of becoming a qualified tumor hypoxia imaging agent. Results: Radiochemcial purity of [^99mTc]Tc(CO)3-CPA-2-NIM was greater than 95% after HPLC purification. Lipophilicity coefficient of this complex was -1.74 ± 0.10 (n = 5, number of experiments), indicating it was a hydrophilic complex. In vitro cell experiments demonstrated that this complex has selectivity for hypoxia at oxygen concentrations < 10 ppm (parts per million). Biodistribution experiment in S180 tumor bearing mice showed that tumor uptake reached its highest at 2 h post-injection with mice tumor-to-muscle ratio. Conclusions: Complex [^99mTc]Tc(CO)3-CPA-2-NIM has the possibility of becoming a tumor hypoxia imaging agent.

Background: Radiopharmaceuticals labeled with [⁶⁸Ga] from positron emission tomography (PET) radionuclides are utilized in nuclear medicine for non-invasive in vivo molecular imaging. Buffer solutions for radiolabeling play an important role as choosing the right buffer for the reaction helps to obtain high yield radiopharmaceuticals. Zwitterionic organic buffer 4-(2- hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), sodium acetate (CH3COONa), sodium bicarbonate (NaHCO3) buffers are widely used for labeling of peptides with [⁶⁸Ga]Cl3. They can be used for peptide labelings with the acidic [⁶⁸Ga]Cl3 precursor of triethanolammonium (TEA) buffer. The cost and toxicity of TAE buffer are relatively low. Method: For [⁶⁸Ga]GaPSMA-HBED-CC and [⁶⁸Ga]GaDOTA-TATE labeling, the effectiveness of TEA buffer without chemical impurities in radiolabeling reactions and QC parameters in successful labeling was investigated. Results: The method used to label [⁶⁸Ga]Cl3 with PSMA-HBED-CC peptide in the presence of TEA buffer was successful when applied at room temperature. High purity radiosynthesis suitable for clinical use was performed to obtain DOTA-TATE peptide with the addition of 363K temperature and radical scavenger. Quality control tests with R-HPLC have shown that this method is suitable for clinical use. Conclusion: We present an alternative procedure for labeling PSMA-HBED-CC and DOTATATE peptides with [⁶⁸GaCl3] to obtain high radioactive doses of final radiopharmaceutical products used in nuclear medicine clinical applications. We have provided a quality-controlled final product that can be used in clinical diagnostic procedures. With the use of an alternative buffer, these methods could be adapted to semi-automatic or automated modules routinely used in nuclear medicine laboratories to label [⁶⁸Ga]-based radiopharmaceuticals.

Background: Chlorins (dihydroporphyrins) are tetrapyrrole-based compounds that are more effective in photodynamic therapy than porphyrins. The instability of the compounds and their oxidation to porphyrin limits the use of these compounds. However, the design and synthesis of new stable chlorin-based cationic photosensitizers with the potential for use in cancer photodynamic therapy can be interesting. Methods: In this research, new tetracationic meso substituted chlorins were designed, synthesized, and characterized. After determining the chemical structure and spectroscopic properties of five new photosensitizers, their phototoxicity on breast cancer cell lines (MCF-7) was investigated under optimized conditions in terms of factors such as photosensitizer concentrations and light intensity. Results: The results of cytotoxicity assayed by the MTT method showed that the synthesized compounds, even up to the concentration of 50 μM had very low toxicity in the absence of light, which indicates their safety under dark conditions. Compounds A1 and A3 with the best physicochemical properties such as solubility, high absorption intensity in the effective range of photodynamic therapy, and the high quantum yield of singlet oxygen, had a good toxic effect (IC50 = 0.5 μM) on the cancer cells (MCF-7) in the presence of laser light. Conclusion: According to the obtained results, compounds A1 and A3 have the potential to continue research on PDT for confirmation and use in treatment.

Background: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off. Methods: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values. Results: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn’t show sufficient classification capability for response or survival. Concusion: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.

Nanotechnology has changed the world, with a great impact on industry and medicine. In this commentary, we discuss the importance of radiolabeled nanomaterials for the construction of theranostic, imaging and therapeutic agents in order to pave the future of medicine.