Lorenzo Lodola | University of Pavia (original) (raw)

Papers by Lorenzo Lodola

Biomedicines

Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ... more Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ago. In vitro tests showed high binding affinity for several types of amyloid fibrils accompanied by an excellent specificity. Initial human studies demonstrated good accuracy in detecting cardiac involvement. Scintigraphy results were confirmed in a group of 28 endomyocardial biopsies. Unfortunately, clinical studies were halted because of a temporary suspension of the vector protein (Trasylol) and public health concerns over prion contamination of the bovine origin compound. To obviate these limitations, efforts have been made to label a recombinant Aprotinin with 99mTc, which exhibits the same affinity for h-insulin fibrils. With the aim of developing a PET tracer, the same recombinant protein was labeled with Gallium. The introduction of a bifunctional chelator did not affect fibril affinity. Finally, a synthetic peptidic fragment, the cyclic 30-51 SS, was synthetized. After direct t...

Nanomaterials, 2021

Nanoparticles of Human Serum Albumin (NC) labelled with 99mTc are widely used in Nuclear Medicine... more 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 purp...

Frontiers in Neuroscience, 2020

The differential diagnosis between brain tumors recurrence and early neuroinflammation or late ra... more The differential diagnosis between brain tumors recurrence and early neuroinflammation or late radionecrosis is still an unsolved problem. The new emerging magnetic resonance imaging, computed tomography, and positron emission tomography diagnostic modalities still lack sufficient accuracy. In the last years, a great effort has been made to develop radiotracers able to detect specific altered metabolic pathways or tumor receptor markers. Our research project aims to evaluate irradiation effects on radiopharmaceutical uptake and compare the kinetic of the fluorinate tracers. T98G glioblastoma cells were irradiated at doses of 2, 10, and 20 Gy with photons, and 18 F-DOPA and 18 F-FET tracer uptake was evaluated. Activity and cell viability at different incubation times were measured. 18 F-FET and 18 F-DOPA are accumulated via the LAT-1 transporter, but 18 F-DOPA is further incorporated, whereas 18 F-FET is not metabolized. Therefore, time-activity curves (TACs) tend to plateau with 18 F-DOPA and to a rapid washout with 18 F-FET. After irradiation, 18 F-DOPA TAC resembles the 18 F-FET pattern. 18 F-DOPA activity peak we observed at 20 min might be fictitious, because earlier time points have not been evaluated, and a higher activity peak before 20 min cannot be excluded. In addition, the activity retained in the irradiated cells remains higher in comparison to the sham ones at all time points investigated. This aspect is similar in the 18 F-FET TAC but less evident. Therefore, we can hypothesize the presence of a second intracellular compartment in addition to the amino acidic pool one governed by LAT-1, which could explain the progressive accumulation of 18 F-DOPA in unirradiated cells.

Contrast Media & Molecular Imaging, 2020

Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) high... more 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 ...

Pleural and Mediastinal Malignancies, 2018

Anticancer Research, 2018

Background/Aim: Glioblastoma is the most malignant and widespread brain tumor in adults, with a r... more Background/Aim: Glioblastoma is the most malignant and widespread brain tumor in adults, with a rapid clinical course. Recently, it has been hypothesized that L-DOPA plays a role in the diagnosis and treatment of glioblastoma. The aim of this study was to assess the effects of pretreatment with L-DOPA on the biological behavior of human T98G cells in vitro. Materials and Methods: T98G cells were treated with 50 μg/ml or 100 μg/ml of L-DOPA for 4 h and their morphology, growth rate, clonogenic survival and migratory capacity in basal conditions and after carbon ion irradiation were evaluated using standard methods. Results: Treated cells showed a lower growth rate and an increased migratory capacity that correlated with the dose of tested L-DOPA. Treatment with L-DOPA increased the growth rate of carbon ion irradiated T98G cells compared to control non-treated cells exposed to the same radiation dose. Conclusion: Our results open further questions about the overall advantage of L-DOPA treatment of glioblastoma. Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, known for its aggressive proliferation and extensive invasion to normal tissue before any symptoms are presented, with long-term survival being extremely rare (1, 2).

Current Issues in Pharmacy and Medical Sciences, 2015

This paper is an report of the investigation of the in vitro binding of 99mTc-DPD for synthetic a... more This paper is an report of the investigation of the in vitro binding of 99mTc-DPD for synthetic amyloid fibrils used for the diagnosis of cardiac amyloidosis (CA), as compared with the use of 99mTc-HMDP and 99mTc-PPI. It also includes an inquiry into the role played by Ca2+ ions and serum proteins on binding to amyloid like materials, as well as the saturability and specificity of DPD for fibrils versus amorphous precipitates (AP). In the work, synthetic insulin fibrils (SIF) and AP were characterized by Congo red staining and TEM imaging. An equal amount of three radiopharmaceuticals were then added to fibrils in Ca2+ (0-4.2 mmol/L) or human serum (HS) adjoined samples and radiopharmaceutical uptake was assessed. To test the saturability of amyloid binding sites, a displacement assays with cold DPD was performed, while adding 50-1500 nmol of 99mTc-DPD to SIF or AP, saturation binding tests were subsequently carried out for evaluating its specificity for amyloid. Herein, synthetic f...

Contrast Media & Molecular Imaging, 2017

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon ... more The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. ​We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our...

World Journal of Radiology, 2016

After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gai... more After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.

Anticancer Research, 2016

Radionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cance... more Radionuclide 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.

Radiology and oncology, 2016

Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often rec... more Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. (18)F-methyl-choline ((18)F-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 (18)F-ethyl-tyrosine ((18)F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. (18)F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate (18)F-FCH and (18)F-FET uptake by human glioblastoma T98G cells. Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10(5) cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medi...

Anticancer research, 2015

Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional mor... more Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional morphological imaging. (18)F-FCH was compared against (18)F-FDG in the T98G glioblastoma cell line with regard to their radiopharmaceutical uptake, in order to test its diagnostic power on brain tumor lesions. Equimolar amounts of (18)F-FCH and (18)F-FDG were added to human glioblastoma T98G cells and human dermal fibroblasts for 20, 40, 60, 90 and 120 min of incubation. Radiopharmaceutical uptake was expressed as a percentage of the administered dose. Cold choline was used for binding competition experiments. In T98G cells (18)F-FCH was taken-up in higher amounts than 18F-FDG after 60 min. In fibroblasts, uptake was lower than 1% for both radiopharmaceuticals. Cold choline reduced the uptake of FCH to 1% similarly to fibroblasts. Our results prove the efficacy of (18)F-FCH as a promising tracer, better than (18)F-FDG in establishing the tumor-to-background ratio in brain tumors.

ABSTRACT Poster presentation

Journal of Labelled Compounds and Radiopharmaceuticals, 2015

Several parameters affect the biodistribution of administered nanocolloids (NC) for Sentinel Lymp... more 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.

European journal of nuclear medicine and molecular imaging

Nuclear Medicine Communications, 2014

The aim of the study was to validate a semiquantitative analytical method to identify the alumini... more The aim of the study was to validate a semiquantitative analytical method to identify the aluminium(III) [Al(III)] concentration in 99Mo/99mTc generator eluates to check the European Pharmacopoeia (Ph. Eur.) requirement (<5 μg/ml). Three different solutions measuring 20 ml - 0.2% 1,10-phenanthroline, 0.05% chrome azurol S and 20% hexamethylenetetramine - were prepared. A cellulose filter paper was subsequently immersed in them, dried overnight at room temperature and cut into rectangles. A volume of 5 μl of first eluates of various 99Mo/99mTc generators was placed onto a reagent paper and the spot colour was compared with a standard aluminium solutions scale (0-100 μg/ml). A cyan/magenta/yellow/key (CMYK) model analysis was adapted to quantify the intensity of colour on the paper, and the presence of aluminium in the eluates was detected by a spectrophotometer. Small changes in standard solution pH (4.1-5.2) and chrome azurol S concentration did not affect the analysis. The cyan channel image analysis was proportional to the Al3+ solution concentration (y=25 019x+1489, R2=0.9554 within 2.5-8 μg/ml). The detection limit for aluminium by the visual test method is about 1 μg/ml, and fading is absent. The cyan channel image analysis method is independent of the observer and is applicable for the evaluation of the chemical purity of 99Mo/99mTc generator eluates. Our colorimetric 'spot test' is advantageous for the visual evaluation of Al pertechnetate concentrations as required by Ph. Eur. showing a sensitivity and a limit of detection superior to that of commercially available spot systems.

Nuclear Medicine Communications, 2014

The aim of the study was to identify deficiencies in product labelling instructions for reconstit... more The aim of the study was to identify deficiencies in product labelling instructions for reconstitution and in the quality control directions detailed in the technical leaflets (TLs) or summary product characteristic (SPC) sheets of commonly used technetium labelling cold kits. The reconstitution and quality control directions in 25 TLs/SPCs were evaluated to identify deficiencies, incompleteness, restrictions, errors, impracticability, and vagueness. In addition, their congruence with the statements given in the relative European Pharmacopoeia (Ph. Eur. VII ed.) monography and diagnostic reference levels of Directive 97/43/EURATOM was evaluated. Deficiencies in information were scored and classified into five categories: 1, absent or incomplete; 2, restrictive; 3, inconsistent or wrong; 4, impractical; and 5, vague. In the 25 documents analyzed a total of 141 deficiencies were found (corresponding to 40.2% of the total scores assigned), and more frequently they pertained to quality control procedures (70.9%), followed by those related to quantitative composition (14.9%), preparation (8.5%), and particle size (5.7%). Nearly 80% of these deficiencies were classified as type 1 - that is, absent or incomplete information. The indications in TLs and SPCs should provide useful information for maintaining the quality and purity of the radiopharmaceutical preparation and ensure the safety level and effectiveness required by law. However, the instructions are often suboptimal or even erroneous, and consequently there are countless failures or difficulties, which represent an impediment to good laboratory practice. We believe that a 'smart' review of radiopharmaceutical documentation would be beneficial in order to align these indications to the real needs of the operators involved in routine in-house nuclear medicine practice.

European Journal of Nuclear Medicine and Molecular Imaging, 2014

ABSTRACT In the recently EANM guidelines on breast sentinel lymph node (SLN) specific activity (S... more ABSTRACT In the recently EANM guidelines on breast sentinel lymph node (SLN) specific activity (SA) of the administered radiocolloid has not been elucidated at all. In clinical application an increase in SLN count rate employing higher SA of albumin nanocolloid has been demonstrated. In contrast following interstitial injection containing higher quantity of labelled albumin in the lower extremities higher lymph-node uptake has been found. Someone else found a better count rate and higher SLN detection rate in prostate cancer using a low SA range. However the use of preparations with high SA has been recommended in the guidelines for the detection of SLN in melanoma. Only very few data on radioactivity distribution related to nanocolloid particle size abundance exists in literature. In conclusion SA must be considered differently if the tracer is used for SLN detection or in lymphoscintigraphy of the extremities and it is an important topic that should be considered in future EANM guidelines.

Biomedicines

Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ... more Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ago. In vitro tests showed high binding affinity for several types of amyloid fibrils accompanied by an excellent specificity. Initial human studies demonstrated good accuracy in detecting cardiac involvement. Scintigraphy results were confirmed in a group of 28 endomyocardial biopsies. Unfortunately, clinical studies were halted because of a temporary suspension of the vector protein (Trasylol) and public health concerns over prion contamination of the bovine origin compound. To obviate these limitations, efforts have been made to label a recombinant Aprotinin with 99mTc, which exhibits the same affinity for h-insulin fibrils. With the aim of developing a PET tracer, the same recombinant protein was labeled with Gallium. The introduction of a bifunctional chelator did not affect fibril affinity. Finally, a synthetic peptidic fragment, the cyclic 30-51 SS, was synthetized. After direct t...

Nanomaterials, 2021

Nanoparticles of Human Serum Albumin (NC) labelled with 99mTc are widely used in Nuclear Medicine... more 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 purp...

Frontiers in Neuroscience, 2020

The differential diagnosis between brain tumors recurrence and early neuroinflammation or late ra... more The differential diagnosis between brain tumors recurrence and early neuroinflammation or late radionecrosis is still an unsolved problem. The new emerging magnetic resonance imaging, computed tomography, and positron emission tomography diagnostic modalities still lack sufficient accuracy. In the last years, a great effort has been made to develop radiotracers able to detect specific altered metabolic pathways or tumor receptor markers. Our research project aims to evaluate irradiation effects on radiopharmaceutical uptake and compare the kinetic of the fluorinate tracers. T98G glioblastoma cells were irradiated at doses of 2, 10, and 20 Gy with photons, and 18 F-DOPA and 18 F-FET tracer uptake was evaluated. Activity and cell viability at different incubation times were measured. 18 F-FET and 18 F-DOPA are accumulated via the LAT-1 transporter, but 18 F-DOPA is further incorporated, whereas 18 F-FET is not metabolized. Therefore, time-activity curves (TACs) tend to plateau with 18 F-DOPA and to a rapid washout with 18 F-FET. After irradiation, 18 F-DOPA TAC resembles the 18 F-FET pattern. 18 F-DOPA activity peak we observed at 20 min might be fictitious, because earlier time points have not been evaluated, and a higher activity peak before 20 min cannot be excluded. In addition, the activity retained in the irradiated cells remains higher in comparison to the sham ones at all time points investigated. This aspect is similar in the 18 F-FET TAC but less evident. Therefore, we can hypothesize the presence of a second intracellular compartment in addition to the amino acidic pool one governed by LAT-1, which could explain the progressive accumulation of 18 F-DOPA in unirradiated cells.

Contrast Media & Molecular Imaging, 2020

Recent developments in sentinel lymph node (SLN) and radio occult lesion localization (ROLL) high... more 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 ...

Pleural and Mediastinal Malignancies, 2018

Anticancer Research, 2018

Background/Aim: Glioblastoma is the most malignant and widespread brain tumor in adults, with a r... more Background/Aim: Glioblastoma is the most malignant and widespread brain tumor in adults, with a rapid clinical course. Recently, it has been hypothesized that L-DOPA plays a role in the diagnosis and treatment of glioblastoma. The aim of this study was to assess the effects of pretreatment with L-DOPA on the biological behavior of human T98G cells in vitro. Materials and Methods: T98G cells were treated with 50 μg/ml or 100 μg/ml of L-DOPA for 4 h and their morphology, growth rate, clonogenic survival and migratory capacity in basal conditions and after carbon ion irradiation were evaluated using standard methods. Results: Treated cells showed a lower growth rate and an increased migratory capacity that correlated with the dose of tested L-DOPA. Treatment with L-DOPA increased the growth rate of carbon ion irradiated T98G cells compared to control non-treated cells exposed to the same radiation dose. Conclusion: Our results open further questions about the overall advantage of L-DOPA treatment of glioblastoma. Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, known for its aggressive proliferation and extensive invasion to normal tissue before any symptoms are presented, with long-term survival being extremely rare (1, 2).

Current Issues in Pharmacy and Medical Sciences, 2015

This paper is an report of the investigation of the in vitro binding of 99mTc-DPD for synthetic a... more This paper is an report of the investigation of the in vitro binding of 99mTc-DPD for synthetic amyloid fibrils used for the diagnosis of cardiac amyloidosis (CA), as compared with the use of 99mTc-HMDP and 99mTc-PPI. It also includes an inquiry into the role played by Ca2+ ions and serum proteins on binding to amyloid like materials, as well as the saturability and specificity of DPD for fibrils versus amorphous precipitates (AP). In the work, synthetic insulin fibrils (SIF) and AP were characterized by Congo red staining and TEM imaging. An equal amount of three radiopharmaceuticals were then added to fibrils in Ca2+ (0-4.2 mmol/L) or human serum (HS) adjoined samples and radiopharmaceutical uptake was assessed. To test the saturability of amyloid binding sites, a displacement assays with cold DPD was performed, while adding 50-1500 nmol of 99mTc-DPD to SIF or AP, saturation binding tests were subsequently carried out for evaluating its specificity for amyloid. Herein, synthetic f...

Contrast Media & Molecular Imaging, 2017

The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon ... more The differential diagnosis between recurrence of gliomas or brain metastases and this phenomenon is important in order to choose the best therapy and predict the prognosis but is still a big problem for physicians. The new emerging MRI, CT, and PET diagnostic modalities still lack sufficient accuracy. Radiolabeled choline and amino acids have been reported to show great tumor specificity. ​We studied the uptake kinetics of [18F]fluoromethyl-choline (FCH) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) by the T98G human glioblastoma cells from 20 to 120 min after irradiation either with photons at 2-10-20 Gy or with carbon ions at 2 Gy (at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy). We also evaluated the cell death and morphology changes induced by radiation treatment. Both FET and FCH are able to trace tumor behavior in terms of higher uptake for increased doses of radiation treatment, due to the upregulation of cells attempts to repair nonlethal damage. Our...

World Journal of Radiology, 2016

After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gai... more After being approved by the National Drug Agency in several countries, Radium-223 (Ra-223) is gaining wide acceptance in the treatment of bone metastatic castration resistant prostate cancer. The exact mechanism of action remain unclear: The established model of direct alpha-particle irradiation from the remodelling bone surface, where Ra-223 accumulates, surrounding the tumor foci can explain a lethal effect only on metastatic microdeposits, but not on higher tumor burden. According to the "pre-metastatic niche model", it is likely that Ra-223 targets several non-tumoral cell types of the tumor microenvironment involved in the complex mechanism of cancer bone homing and colonization. A deeper insight into this hypothetical mechanism will lead to a more accurate dosimetric approach and to find optimal sequencing and/or combination with the other therapeutic options.

Anticancer Research, 2016

Radionuclide therapy is known to deliver ionizing radiation to tumor sites, thereby killing cance... more Radionuclide 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.

Radiology and oncology, 2016

Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often rec... more Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. (18)F-methyl-choline ((18)F-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 (18)F-ethyl-tyrosine ((18)F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. (18)F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate (18)F-FCH and (18)F-FET uptake by human glioblastoma T98G cells. Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10(5) cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medi...

Anticancer research, 2015

Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional mor... more Tumor and chemo/radiotherapy-damaged brain tissues are hardly distinguishable by conventional morphological imaging. (18)F-FCH was compared against (18)F-FDG in the T98G glioblastoma cell line with regard to their radiopharmaceutical uptake, in order to test its diagnostic power on brain tumor lesions. Equimolar amounts of (18)F-FCH and (18)F-FDG were added to human glioblastoma T98G cells and human dermal fibroblasts for 20, 40, 60, 90 and 120 min of incubation. Radiopharmaceutical uptake was expressed as a percentage of the administered dose. Cold choline was used for binding competition experiments. In T98G cells (18)F-FCH was taken-up in higher amounts than 18F-FDG after 60 min. In fibroblasts, uptake was lower than 1% for both radiopharmaceuticals. Cold choline reduced the uptake of FCH to 1% similarly to fibroblasts. Our results prove the efficacy of (18)F-FCH as a promising tracer, better than (18)F-FDG in establishing the tumor-to-background ratio in brain tumors.

ABSTRACT Poster presentation

Journal of Labelled Compounds and Radiopharmaceuticals, 2015

Several parameters affect the biodistribution of administered nanocolloids (NC) for Sentinel Lymp... more 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.

European journal of nuclear medicine and molecular imaging

Nuclear Medicine Communications, 2014

The aim of the study was to validate a semiquantitative analytical method to identify the alumini... more The aim of the study was to validate a semiquantitative analytical method to identify the aluminium(III) [Al(III)] concentration in 99Mo/99mTc generator eluates to check the European Pharmacopoeia (Ph. Eur.) requirement (<5 μg/ml). Three different solutions measuring 20 ml - 0.2% 1,10-phenanthroline, 0.05% chrome azurol S and 20% hexamethylenetetramine - were prepared. A cellulose filter paper was subsequently immersed in them, dried overnight at room temperature and cut into rectangles. A volume of 5 μl of first eluates of various 99Mo/99mTc generators was placed onto a reagent paper and the spot colour was compared with a standard aluminium solutions scale (0-100 μg/ml). A cyan/magenta/yellow/key (CMYK) model analysis was adapted to quantify the intensity of colour on the paper, and the presence of aluminium in the eluates was detected by a spectrophotometer. Small changes in standard solution pH (4.1-5.2) and chrome azurol S concentration did not affect the analysis. The cyan channel image analysis was proportional to the Al3+ solution concentration (y=25 019x+1489, R2=0.9554 within 2.5-8 μg/ml). The detection limit for aluminium by the visual test method is about 1 μg/ml, and fading is absent. The cyan channel image analysis method is independent of the observer and is applicable for the evaluation of the chemical purity of 99Mo/99mTc generator eluates. Our colorimetric 'spot test' is advantageous for the visual evaluation of Al pertechnetate concentrations as required by Ph. Eur. showing a sensitivity and a limit of detection superior to that of commercially available spot systems.

Nuclear Medicine Communications, 2014

The aim of the study was to identify deficiencies in product labelling instructions for reconstit... more The aim of the study was to identify deficiencies in product labelling instructions for reconstitution and in the quality control directions detailed in the technical leaflets (TLs) or summary product characteristic (SPC) sheets of commonly used technetium labelling cold kits. The reconstitution and quality control directions in 25 TLs/SPCs were evaluated to identify deficiencies, incompleteness, restrictions, errors, impracticability, and vagueness. In addition, their congruence with the statements given in the relative European Pharmacopoeia (Ph. Eur. VII ed.) monography and diagnostic reference levels of Directive 97/43/EURATOM was evaluated. Deficiencies in information were scored and classified into five categories: 1, absent or incomplete; 2, restrictive; 3, inconsistent or wrong; 4, impractical; and 5, vague. In the 25 documents analyzed a total of 141 deficiencies were found (corresponding to 40.2% of the total scores assigned), and more frequently they pertained to quality control procedures (70.9%), followed by those related to quantitative composition (14.9%), preparation (8.5%), and particle size (5.7%). Nearly 80% of these deficiencies were classified as type 1 - that is, absent or incomplete information. The indications in TLs and SPCs should provide useful information for maintaining the quality and purity of the radiopharmaceutical preparation and ensure the safety level and effectiveness required by law. However, the instructions are often suboptimal or even erroneous, and consequently there are countless failures or difficulties, which represent an impediment to good laboratory practice. We believe that a 'smart' review of radiopharmaceutical documentation would be beneficial in order to align these indications to the real needs of the operators involved in routine in-house nuclear medicine practice.

European Journal of Nuclear Medicine and Molecular Imaging, 2014

ABSTRACT In the recently EANM guidelines on breast sentinel lymph node (SLN) specific activity (S... more ABSTRACT In the recently EANM guidelines on breast sentinel lymph node (SLN) specific activity (SA) of the administered radiocolloid has not been elucidated at all. In clinical application an increase in SLN count rate employing higher SA of albumin nanocolloid has been demonstrated. In contrast following interstitial injection containing higher quantity of labelled albumin in the lower extremities higher lymph-node uptake has been found. Someone else found a better count rate and higher SLN detection rate in prostate cancer using a low SA range. However the use of preparations with high SA has been recommended in the guidelines for the detection of SLN in melanoma. Only very few data on radioactivity distribution related to nanocolloid particle size abundance exists in literature. In conclusion SA must be considered differently if the tracer is used for SLN detection or in lymphoscintigraphy of the extremities and it is an important topic that should be considered in future EANM guidelines.