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Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) highlight the need for a multimodal contrast agent, providing better presurgical PET imaging and improved intraoperative mapping thanks to fluorescence detection. For this reason, we have studied a trimodal SLN/ROLL targeting agent (99mTc-68Ga-ICG) with commercially available kits of macroaggregated or nanocolloidal albumin (MA/NC-HSA). 68Ga PET imaging does provide better spatial resolution and makes it possible to predict signal intensity during surgery. The presence of 99mTc assesses the efficacy of these compounds in vitro and also during the surgery procedure. The aim of this study was to optimise the labelling and tagging of these two radiopharmaceuticals and assess their yields and stability. Kits of MA/NC-HSA particles (Pulmocis® and NanoAlbumon®) were used for sequential radiolabelling with 99mTc and 68Ga. Fluorescent tagging was performed using indocyanine green, a tricarbocyanine dye. The ITLC radiochemical purity of the trilabelled MA/NC-HSA was >95%. Fluorescent purity was measured by scanning the strips with a PhotoDynamicEye probe. Finally, in vitro stability tests, performed with DTPA and human serum solutions, assessed the efficacy of fluorescent tagging and radiolabelling.

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Several parameters affect the biodistribution of administered nanocolloids (NC) for Sentinel Lymph Node (SLN) detection: particle size distribution, number of Tc atoms per particle and specific activity (SA). Relatively few data are available with frequently conflicting results. (99m)Tc-NC-human serum albumin (HSA) Nanocoll®, Nanoalbumon® and Nanotop® were analysed for particles' dimensional and radioactivity distribution, and a mathematical model was elaborated to estimate the number of particles involved. Commercially available kits were reconstituted at maximal SA of 11 MBq/µg HSA. Particles size distribution was evaluated by Dynamic Light Scattering. These data were related to the radioactivity distribution analysis passing labelled NC through three polycarbonate filters (15-30-50-nm pore size) under vacuum. Highest radioactivity was carried by 30-50 nm particles. The smallest ones, even though most numerous, carried only the 10% of (99m)Tc atoms. Nanocoll and Nanotop are not significantly different, while Nanoalbumon is characterized by largest particles (>30 nm) that carried the most of radioactivity (80%). Smallest particles could saturate the clearing capacity of macrophages; therefore, if the tracer is used for SLN detection, more node tiers could be visualized, reducing accuracy of SLN mapping. Manufacturers could implement technical leaflets with particle size distribution and could improve the labelling protocol to provide clinicians useful information.

Nanoparticles of Human Serum Albumin (NC) labelled with 99mTc are widely used in Nuclear Medicine and represent the gold-standard for the intraoperative detection of the sentinel lymph node in many kinds of cancer, mainly breast cancer and melanoma. A significant amount of radionuclides can be incorporated into the HSA particle, due to the multiple binding sites, and HSA-based nanocolloid catabolism is a fast and easy process that results in innocuous degradation products. NCs labelled with different isotopes represent an interesting radiopharmaceutical for extending diagnostic accuracy and surgical outcome, but the knowledge of the chemical bond between NCs and isotopes has not been fully elucidated, including information on its strength and specificity. The aim of this study is to investigate and compare the physicochemical characteristics of the bond between NCs and 99mTc and 68Ga isotopes. Commercial kits of HSA-based nanocolloid particles (NanoAlbumon®) were used. For this purpose, we have primarily studied the kinetic orders of NC radiolabelling. Langmuir isotherms and pH effect on radiolabelling were tested and the stability of the radiometal complex was verified through competition reactions carried out in presence of different ligands. The future goal of our research is the development of inexpensive and instant kits, easily labelled with a wide spectrum of diagnostic and therapeutic isotopes, thus facilitating the availability of versatile and multipurpose radiopharmaceuticals.

BackgroundDespite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18F-methyl-choline (18F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18F-ethyl-tyrosine (18F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18F-FCH and 18F-FET uptake by human glioblastoma T98G cells.Material and methodsHuman glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 105 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18F-FCH and 18F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 105 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05.ResultsA significant uptake of 18F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18F-FET in comparison to 18F-FCH was lower by a factor of more than 3, with different kinetic curves.18F-FET showed a more rapid initial uptake up to 40 minutes and 18F-FCH showed a progressive rise reaching a maximum after 90 minutes.Conclusions18F-FCH and 18F-FET are candidates for neuro-oncological PET imaging. 18F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of 18F-FCH to inflammatory cells makes it more difficult to discriminate between tumour persistence and non-neoplastic changes. Additional studies on the influence of inflammatory tissue and radionecrotic cellular components on radiopharmaceutical uptake are necessary.

Background: Macroaggregated human serum albumin (MAA) properties are widely used in nuclear medicine, labelled with 99mTc. The aim of this study is to improve the knowledge about the morphology, size, dimension and physical–chemical characteristics of MAA and their bond with 99mTc and 68Ga. Methods: Commercial kits of MAA (Pulmocis®) were used. Characterisation through experiments based on SEM, DLS and Stokes’ Law were carried out. In vitro experiments for Langmuir isotherms and pH studies on radiolabelling were performed and the stability of the radiometal complex was verified through competition reactions. Results: The study settles the MAA dimension within the range 43–51 μm. The Langmuir isotherm reveals for [99mTc]MAA: Bmax (46.32), h (2.36); for [68Ga]MAA: Bmax (44.54), h (0.893). Dual labelling reveals that MAA does not discriminate different radioisotopes. Experiments on pH placed the optimal pH for labelling with 99mTc at 6. Conclusion: Radiolabelling of MAA is possible with high efficiency. The nondiscriminatory MAA bonds make this drug suitable for radiolabelling with different radioisotopes or for dual labelling. This finding illustrates the need to continue investigating MAA chemical and physical characteristics to allow for secure labelling with different isotopes.

Abstract. 223 Prostate cancer (PCa) is the most common malignancy in men (1). In patients affected by advanced PCa, defined as hormonesensitive disease since the tumor still requires androgen for growth, androgen deprivation therapy (ADT), including luteinizing hormone-releasing hormone (LHRH) agonists, antagonists and anti-androgens, represents the first-line treatment. Unfortunately some cancer cells develop resistance to ADT, indicating the progression of the disease to metastatic castration-resistant prostate cancer (mCRPCa). Such resistance to castration occurs in most patients (2) and, despite the approval of new therapeutic agents, mCRPCa remains a lethal disease (3). Nowadays the new therapeutic landscape for patients affected by mCRPCa aims to extend overall survival (OS) and includes cytotoxic, new-generation anti-androgens, immunotherapeutics and radiopharmaceuticals (4, 5).Bones are the preferred site of metastasis. Almost 90% of men who die from PCa have bone-metastatic disease (6), with a 5-year OS rate of 20%. Due to the fragility of bone with metastases, with the related risk of pain, fractures, spinal cord compression and hematological consequences, several drugs have been developed to treat the osseous involvement of this disease. In previous years, the optimal treatment aimed to relieve pain and reduce skeletal morbidity.Besides systemic therapies, bone-targeted agents that focus their activity on bone, such as bisphosphonates, monoclonal antibody and radiopharmaceuticals, have become available. The bisphosphonate zoledronic acid, the antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) denosumab and radiopharmaceuticals [such as 89 Sr and 153 Sm-ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP)], were approved for delaying skeletal-related events (SREs) and for the palliation of bone pain from mCRPCa. Radionuclide TherapyRadionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cancer cells (7). Bone-targeted radiopharmaceuticals localize their radiation to sites of high bone remodeling. 5719