Biomimetic Keratin-Coated Gold Nanoparticles for Photo-Thermal Therapy in a 3D Bioprinted Glioblastoma Tumor Model.

Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribution of fluorescent-labeled Ker-AuNPs in the volume and their capability to enter the cells. Laser-assisted (λ = 532 nm) PTT experiments demonstrate the extraordinary ability of Ker-AuNPs to generate heating, producing the highest temperature rise of about 16 °C in less than 2 min.

Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting (223)Ra-dichloride.

PURPOSE: Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. METHODS: The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for (223)Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on (99m)Tc-MDP whole-body images, and the ROIs superimposed on the (223)Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. RESULTS: In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T 1/2eff) of (223)Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy. Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D RBE = 899 mGy/MBq (range 340-2,450 mGy/MBq). The percent uptake of (99m)Tc and (223)Ra (activity extrapolated to t = 0) were significantly correlated. CONCLUSION: The feasibility of in vivo quantitative imaging in (223)Ra therapy was confirmed. The lesion uptake of (223)Ra-dichloride was significantly correlated with that of (99m)Tc-MDP. The D RBE to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D RBE was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with (223)Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes.

18F-fluorodeoxyglucose (18F-FDG) Functionalized Gold Nanoparticles (GNPs) for Plasmonic Photothermal Ablation of Cancer: A Review.

The meeting and merging between innovative nanotechnological systems, such as nanoparticles, and the persistent need to outperform diagnostic-therapeutic approaches to fighting cancer are revolutionizing the medical research scenario, leading us into the world of nanomedicine. Photothermal therapy (PTT) is a non-invasive thermo-ablative treatment in which cellular hyperthermia is generated through the interaction of near-infrared light with light-to-heat converter entities, such as gold nanoparticles (GNPs). GNPs have great potential to improve recovery time, cure complexity, and time spent on the treatment of specific types of cancer. The development of gold nanostructures for photothermal efficacy and target selectivity ensures effective and deep tissue-penetrating PTT with fewer worries about adverse effects from nonspecific distributions. Regardless of the thriving research recorded in the last decade regarding the multiple biomedical applications of nanoparticles and, in particular, their conjugation with drugs, few works have been completed regarding the possibility of combining GNPs with the cancer-targeted pharmaceutical fluorodeoxyglucose (FDG). This review aims to provide an actual scenario on the application of functionalized GNP-mediated PTT for cancer ablation purposes, regarding the opportunity given by the 18F-fluorodeoxyglucose (18F-FDG) functionalization.

A new generation of scintillation detectors with identification of events undergoing multiple interactions for gamma-ray imaging and spectroscopy.

The present work deals with a scintillation detector made of a LuYAP:Ce array coupled to a position-sensitive photo-multiplier tube, whose structure is well suitable for SPECT and PET, but also in nuclear physics, astrophysics, astroparticle physics, homeland security, and non-proliferation. The response was investigated under Co-57, Ba-133, Cs-137 gamma-ray irradiation, and with Lu-176 self-activity. The investigation, based on the 2-D charge-profiles spread, provides means for identifying and rejecting multiple-interactions in the crystal-array, like Lu X-ray escape photons, and Compton-scattered ones.

Diagnostic Value of the Early Heart-to-Mediastinum Count Ratio in Cardiac 123I-mIBG Imaging for Parkinson's Disease.

BACKGROUND: Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role. In this prospective study, a threshold for the early Heart-to-Mediastinum (H/M) count ratio has been investigated, obtaining a diagnostic accuracy analogous to conventional, delayed imaging. METHODS: One hundred and eight patients with suspected Parkinson's disease (PD) were acquired after 15 and 240 minutes from the injection of 150-185 MBq of 123I-mIBG. The early and late H/M (He/Me and Hl/Ml) were evaluated by drawing Region-of-Interests on the heart and the upper half of the mediastinum. Optimal threshold (Youden index) and overall predictive performance were determined by receiver operating characteristic curve, classifying tentatively patients having an Hl/Ml lower than 1.6 as suffering from PD. RESULTS: He/Me was not significantly different from Hl/Ml (p-value=0.835). The Area-under-curve was 0.935 (95%CI: 0.845-1.000). The He/Me optimal threshold was 1.66, with sensitivity, specificity, and diagnostic accuracy of 95.5%, 85.7 and 90.7% respectively. CONCLUSION: The He/Me Ratio is almost as accurate as the widely used delayed 123I-mIBG imaging, reducing the burden of delayed imaging but preserving the diagnostic accuracy of the method. Moreover the differential diagnosis in Parkinson's disease can be made in just 25 minutes against the 4 hours currently needed, lowering costs of the healthcare system and improving patients compliance.

Gonioprobe, an Innovative Gamma-probe to Guide Parathyroid Radioguided Surgery: First Clinical Experiences with Navigator and Lock-ontarget Functions.

BACKGROUND: Radioguided surgery represents a validated technique for the detection and the excision of abnormal parathyroid glands responsible for primary hyperparathyroidism (PHPT). To date little attention has been paid as to how the characteristics of gamma-probes can influence surgical procedure and time, thus having an impact on postoperative morbidity, hospitalization and costs. METHODS: We designed a new prototype of gamma-probe, the Gonioprobe, and tested its clinical utility in the operating room. Gonioprobe, thanks to its 5 scintillating independent crystals, performs the dual function of Navigator and Lock-on-target. These characteristics allow the immediate guidance of the surgeon's hand towards the source with very high precision, and with a much higher spatial resolution than commercial probes. Gonioprobe was used during intervention to detect abnormal parathyroid tissue, and to ensure no radioactivity in surgery bed after adenoma removal. RESULTS: We tested our gamma-probe on parathyroid adenomas particularly difficult to identify at a visual inspection due to anatomy modifications from previous neck surgery and/or characterized by uncommon localization. Moreover, parathyroid adenomas were hardly removable due to the proximity to the esophagus, neck vessels and/or recurrent laryngeal nerve (RLN). An intraoperative nerve monitoring system was used to protect the recurrent laryngeal nerve from injuries. Parathyroid hormone (PTH) assay and frozen biopsy confirmed the successful excision of the adenomas. CONCLUSION: The intraoperative use of the innovative Gonioprobe along with the nerve monitoring system allowed an accurate and safe removal of parathyroid adenomas and offered a significant advantage by reducing surgical time and postoperative complications, as well as hospitalization and costs.

Biomimetic keratin gold nanoparticle-mediated in vitro photothermal therapy on glioblastoma multiforme.

Aim: To realize and characterize a new generation of keratin-coated gold nanoparticles (Ker-AuNPs) as highly efficient photosensitive nanosized therapeutics for plasmonic photothermal (PPT) therapy. Materials & methods: The chemical, physical, morphological and photothermal properties of Ker-AuNPs are investigated using dynamic light scattering, ζ-potential, UV-Visible, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, transmission electron microscopy and high-resolution thermography. In vitro experiments are performed on a human glioblastoma cell line (i.e., U87-MG), using viability assays, transmission electron microscopy, fluorescence microscopy, cytometric analyses and PPT experiments. Results: Experiments confirm the excellent biocompatibility of Ker-AuNPs, their efficient cellular uptake and localized photothermal heating capabilities. Conclusion: The reported structural and functional properties pointed out these Ker-AuNPs as a promising new tool in the field of biocompatible photothermal agents for PPT treatments against cancer-related diseases.

New Frontiers in Molecular Imaging with Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Efficacy, Toxicity, and Future Applications.

Supermagnetic Iron Oxide Nanoparticles (SPIONs) are nanoparticles that have an iron oxide core and a functionalized shell. SPIONs have recently raised much interest in the scientific community, given their exciting potential diagnostic and theragnostic applications. The possibility to modify their surface and the characteristics of their core make SPIONs a specific contrast agent for magnetic resonance imaging but also an intriguing family of tracer for nuclear medicine. An example is 68Ga-radiolabeled bombesin-conjugated to superparamagnetic nanoparticles coated with trimethyl chitosan that is selective for the gastrin-releasing peptide receptors. These receptors are expressed by several human cancer cells such as breast and prostate neoplasia. Since the coating does not interfere with the properties of the molecules bounded to the shell, it has been proposed to link SPIONs with antibodies. SPIONs can be used also to monitor the biodistribution of mesenchymal stromal cells and take place in various applications. The aim of this review of literature is to analyze the diagnostic aspect of SPIONs in magnetic resonance imaging and in nuclear medicine, with a particular focus on sentinel lymph node applications. Moreover, it is taken into account the possible toxicity and the effects on human physiology to determine the SPIONs' safety.

Analysis of Unusual Adverse Effects After Radium-223 Dichloride Administration.

BACKGROUND: To our knowledge, no previous study or literature review has been performed about the effects of the extravasation of therapeutic radiopharmaceutical agents and its potential consequences, especially regarding alpha-particle emitting radiopharmaceuticals. METHODS: Even if Radium-223 dichloride is known to be a relatively safe drug to manage, despite the correctness of the procedures applied , unexpected delayed adverse effects can occur. In our vast experience, we rarely observed lymphedema, even after some time, at the site of administration. RESULTS: Management of lymphedema caused by radiopharmaceuticals administration has been addressed through clinical examples. The sudden intervention allowed a fast remission of the signs and symptoms complained by patients treated with Radium-223 dichloride. CONCLUSION: The management of adverse effects after radiopharmaceuticals administration as in case of lymphedema onset, is extremely simple. These data confirm the safety of Radium-223 treatment.

Stimuli-responsive nanoparticle-assisted immunotherapy: a new weapon against solid tumours.

Although significant improvements in cancer treatment have led to a longer survival period, the death rate of patients with solid tumours has not changed during the last decades. Most researchers are currently concentrating on defining the mechanisms of the different resistance pathways activated by tumour cells; meanwhile, the role of limited drug distribution within tumours has been neglected. The application of nanotechnology in medicine offers unexplored opportunities for realizing a new generation of anticancer therapies that can overcome the physical hindrances that characterize solid tumours. Indeed, surface-engineered nanoparticles (NPs) (both organic and inorganic) have been used as powerful tools in cancer therapy. Particularly, Au NPs have been utilized to develop a new drug-free treatment, photo-thermal therapy (PTT), due to their stimuli-responsive properties. PTT combined with immunotherapy represents a major breakthrough in the fight against malignant solid tumours. In this review, we provide a complete overview of the synergistic approaches based on PTT and immunotherapy, considering the selection, design, and functionalization of the NPs and their thermo-optical properties, moving to in vivo studies and finally to clinical trial applications in patients suffering from solid tumours.

Psychopathology of excitatory and compulsive aspects of vandalistic graffiti.

In this paper were explored psychological themes underlying vandalistic graffiti by 162 Italian adolescents (154 boys, 8 girls; M age = 17.5 yr., SD = 2.3) who "felt hooked" on vandalistic graffiti and agreed to participate in an interview with a graffiti writer. Use of this interview could clarify the motivations which led these youths to write on walls, the meaning they give to that act, the emotions they feel as they write, and their perception of risks and excitement involved. Qualitative analysis of their responses suggested these adolescents present a marked excitatory-compulsive trait, report a sense of emptiness, boredom, loneliness, and a lack of internal points of reference, and adopt behaviors linked to a pressing need for immediate gratification.

Variable tilt-angle, parallel-hole collimation system for high-resolution molecular imaging gamma tomosynthesis.

PURPOSE: This study investigates a novel gamma tomosynthesis (GT) method based on a variable tilt-angle, parallel-hole collimator (VAPHC) which, mounting to a conventional gamma, is able to perform high-resolution three-dimensional imaging. METHODS: The VAPHC has the remarkable feature to be modular, consisting of independent collimation elements able to tilt according to variable angles [-45° to +45°]. Spatial resolutions were measured in reconstructed GT images using a point source at different source-to-collimator distances, while sensitivity was evaluated over the range of slant angles using a disk-source. Image contrast (IC) and contrast-to-noise-ratio (CNR) of sub-centimeters tumors were evaluated using a breast phantom containing a background activity and spheres filled with 99mTc to simulate lesions at two depths. Breast phantom GT images were compared with planar and circular-orbit SPECT acquisitions of equal scan-time. RESULTS: Planar spatial resolutions range from 9 to 14 mm over a depth range of 6-10 cm; spatial resolution in depth dimension becomes two times greater than those in the other dimensions. The measured sensitivity decreases from 9 cps/µCi to 6 cps/µCi varying the slant angle from 5° to 45°. The measured IC and CNR of GT reconstructed images demonstrated that it was possible to improve the spatial resolution/sensitivity trade-off. CONCLUSIONS: The proposed GT based VAPHC demonstrated the potential for superior spatial resolution and contrast compared to planar and SPECT acquisitions. A conventional gamma camera equipped with the VAPHC could be located at the minimum distance from the patient, thus improving detection, localisation and characterisation of sub-centimetre lesions.

Scintigraphic load of bone disease evaluated by DASciS software as a survival predictor in metastatic castration-resistant prostate cancer patients candidates to 223RaCl treatment.

Background Aim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of "Sapienza" University of Rome for BSI calculation. Patients and methods 127 mCRPC patients bone scan images were processed with DASciS software, and BSI was tested as OS predictor. Results 546 bone scans were analyzed revealing that the extension of disease is a predictor of OS (0-3% = 28 months of median survival (MoMS]; 3%-5% = 11 MoMS, > 5% = 5 MoMS). BSI has been analyzed as a single parameter for OS, determining an 88% AUC. Moreover, the composition between the BSI and the 3-PS (3-variable prognostic score) determines a remarkable improvement of the AUC (91%), defining these two parameters as the best OS predictors. Conclusions This study suggests that OS is inversely correlated with the load of bone disease in mCRPC Ra-223-treated subjects. DASciS software appears a promising tool in identifying mCRPC patients that more likely take advantage from Ra-223 treatment. BSI is proposed as a predictive variable for OS and included to a multidimensional clinical evaluation permits to approach the patients' enrollment in a rational way, allowing to enhance the treatment effectiveness together with cost optimization.

A 3-variable prognostic score (3-PS) for overall survival prediction in metastatic castration-resistant prostate cancer treated with 223Radium-dichloride.

OBJECTIVE: In mCRPC patients treated with 223Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving 223Ra treatment. METHODS: 92 consecutive CRPC patients with symptomatic bone metastases receiving 223Ra treatment were included. Available baseline clinical data relevant to the survival analysis were retrospectively collected. The primary end-point of the study was overall survival, which was established from the first 223Ra administration until date of death from any cause. RESULTS: Median follow-up time from the first 223Ra administration was 6 months (range 1-31 months). The univariate analysis evaluating the prognostic value of all baseline clinical variables showed that patients' weight, BMI, ECOG PS, Hb and tALP values were independently associated with OS. On multivariable analysis only baseline Hb value and ECOG PS remained significantly correlated with OS. To determine reliable baseline predictive factors for survival in patients receiving 223Ra treatment, we produced a predictive score. We tried all possible variable combinations, and found that the best score was obtained by combining baseline ECOG PS with Hb < 12 g/dl and PSA ≥ 20 ng/ml. This resulted in a score ranging from 0 to 4, with AUC 78.4% (p < 0.001). CONCLUSIONS: We propose a multidimensional clinical evaluation to select those mCRPC subjects suitable to receive the maximum benefit from 223Ra treatment.

The MINDVIEW project: First results.

We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient. The achieved spatial resolution, close to 1 mm, will enable differentiation of relevant brain structures for schizophrenia. A cost-effective and simple method of radiopharmaceutical production from 11C-carbon monoxide and a mini-clean room has been demonstrated. It has been shown that 11C-raclopride has higher binding potential in a new VAAT null mutant mouse model of schizophrenia compared to wild type control animals. A significant reduction in TSPO binding has been found in gray matter in a small sample of drug-naïve, first episode psychosis patients, suggesting a reduced number or an altered function of immune cells in brain at early stage schizophrenia.

Gamma camera calibrations for the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases.

PURPOSE: The aim was to calibrate gamma cameras in the framework of the Italian multicentre study for lesion dosimetry in 223Ra therapy of bone metastases. Equipments of several manufacturers and different models were used. METHODS: Eleven gamma cameras (3/8- and 5/8-inch crystal) were used, acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air, varying source-detector distance and source size. Transmission curves were measured, calculating the parameters used for attenuation/scatter correction with the pseudo-extrapolation number method, and assessing their variations with the source size. RESULTS: Values of the calibration factor (geometric mean of both detector sensitivities) ranged from 41.1 to 113.9cps/MBq. For the smallest source (diameter of 3.5cm), the calibration factor decrease ranged from -30% to -4%, highlighting the importance of partial volume effects according to the equipment involved. The sensitivity variation with the source-detector distance, with respect to the 15cm-value, reached 10% (in absolute value) in the range 5-30cm, but fixing the distance between the two heads, the calibration factor variation with the distance from the midline was within 3.6%. Appreciable variation of the transmission curves with the source size were observed, examining the results obtained with six gamma cameras. CONCLUSION: Assessments of sensitivity and transmission curve variations with source size should be regularly implemented in calibration procedures. The results of this study represent a useful compendium to check the obtained calibrations for dosimetric purposes.

Phantom validation of quantitative Y-90 PET/CT-based dosimetry in liver radioembolization.

BACKGROUND: PET/CT has recently been shown to be a viable alternative to traditional post-infusion imaging methods providing good quality images of 90Y-laden microspheres after selective internal radiation therapy (SIRT). In the present paper, first we assessed the quantitative accuracy of 90Y-PET using an anthropomorphic phantom provided with lungs, liver, spine, and a cylindrical homemade lesion located into the hepatic compartment. Then, we explored the accuracy of different computational approaches on dose calculation, including (I) direct Monte Carlo radiation transport using Raydose, (II) Kernel convolution using Philips Stratos, (III) local deposition algorithm, (IV) Monte Carlo technique (MCNP) considering a uniform activity distribution, and (V) MIRD (Medical Internal Radiation Dose) analytical approach. Finally, calculated absorbed doses were compared with those obtained performing measurements with LiF:Mg,Cu,P TLD chips in a liquid environment. RESULTS: Our results indicate that despite 90Y-PET being likely to provide high-resolution images, the 90Y low branch ratio, along with other image-degrading factors, may produce non-uniform activity maps, even in the presence of uniform activity. A systematic underestimation of the recovered activity, both for the tumor insert and for the liver background, was found. This is particularly true if no partial volume correction is applied through recovery coefficients. All dose algorithms performed well, the worst case scenario providing an agreement between absorbed dose evaluations within 20%. Average absorbed doses determined with the local deposition method are in excellent agreement with those obtained using the MIRD and the kernel-convolution dose calculation approach. Finally, absorbed dose assessed with MC codes are in good agreement with those obtained using TLD in liquid solution, thus confirming the soundness of both calculation approaches. This is especially true for Raydose, which provided an absorbed dose value within 3% of the measured dose, well within the stated uncertainties. CONCLUSIONS: Patient-specific dosimetry is possible even in a scenario with low true coincidences and high random fraction, as in 90Y-PET imaging, granted that accurate absolute PET calibration is performed and acquisition times are sufficiently long. Despite Monte Carlo calculations seeming to outperform all dose estimation algorithms, our data provide a strong argument for encouraging the use of the local deposition algorithm for routine 90Y dosimetry based on PET/CT imaging, due to its simplicity of implementation.

Principal component analysis of scintimammographic images.

The recent development of new gamma imagers based on scintillation array with high spatial resolution, has strongly improved the possibility of detecting sub-centimeter cancer in Scintimammography. However, Compton scattering contamination remains the main drawback since it limits the sensitivity of tumor detection. Principal component image analysis (PCA), recently introduced in scintimam nographic imaging, is a data reduction technique able to represent the radiation emitted from chest, breast healthy and damaged tissues as separated images. From these images a Scintimammography can be obtained where the Compton contamination is "removed". In the present paper we compared the PCA reconstructed images with the conventional scintimammographic images resulting from the photopeak (Ph) energy window. Data coming from a clinical trial were used. For both kinds of images the tumor presence was quantified by evaluating the t-student statistics for independent sample as a measure of the signal-to-noise ratio (SNR). Since the absence of Compton scattering, the PCA reconstructed images shows a better noise suppression and allows a more reliable diagnostics in comparison with the images obtained by the photopeak energy window, reducing the trend in producing false positive.

High resolution scintimammography helps in differentiating benign from malignant findings in scintigraphic hot spots.

Several efforts have been focusing on the development of detectors devoted to high solution (99m)Tc sestamibi scintimammography to improve sensitivity for non palpable lesions. To this aim new high resolution scintillation gamma camera was developed under the "Integiated Mammographic Imaging" project. The gamma camera, made by CAEN and Pol.Hi.Tech, has an overall dimension of 112x120x75mm3. It consists of an array of 1 in. PSPMTs Hamamatsu H8520-C12 closely packed, a NaI(T1) scintillation array (1.8x1.8x6mm(3) pixel) and a general purpose collimator. By this gamma camera a clinical experience on a few patients with breast cancer suspicion was performed. In this paper we show how high resolution approach allows to better categorize the lesions on the basis of the morphology of the spatial distribution of the radiotracer in the breast tissue. By comparing conventional and high resolution images of a young patient (29 y.o.) with breast cancer suspicion, it appears clear how the Anger, camera images showed a defined hot spot, highly suggestive of malignant lesion; on the contrary, the high resolution scan shown a large and inhomogeneous uptake area with the absence of clear and focal character of the uptake, to be considered as a probably non malignant lesions. This resuh was confirmed by byoptical findings that diagnosed the echographic findings as a benign inflammatory lesion.

The Italian multicentre dosimetric study for lesion dosimetry in 223Ra therapy of bone metastases: Calibration protocol of gamma cameras and patient eligibility criteria.

PURPOSE: The aims of this work were to explore patient eligibility criteria for dosimetric studies in 223Ra therapy and evaluate the effects of differences in gamma camera calibration procedures into activity quantification. METHODS: Calibrations with 223Ra were performed with four gamma cameras (3/8-inch crystal) acquiring planar static images with double-peak (82 and 154keV, 20% wide) and MEGP collimator. The sensitivity was measured in air by varying activity, source-detector distance, and source diameter. Transmission curves were measured for attenuation/scatter correction with the pseudo-extrapolation number method, varying the experimental setup. 223Ra images of twenty-five patients (69 lesions) were acquired to study the lesions visibility. Univariate ROC analysis was performed considering visible/non visible lesions on 223Ra images as true positive/true negative group, and using as score value the lesion/soft tissue contrast ratio (CR) derived from 99mTc-MDP WB scan. RESULTS: Sensitivity was nearly constant varying activity and distance (maximum s.d.=2%). Partial volume effects were negligible for object area ⩾960mm2. Transmission curve measurements are affected by experimental setup and source size, leading to activity quantification errors up to 20%. The ROC analysis yielded an AUC of 0.972 and an optimal threshold of CR of 10, corresponding to an accuracy of 92%. CONCLUSION: The minimum calibration protocol requires sensitivity and transmission curve measurements varying the object size, performing a careful procedure standardisation. Lesions with 99mTc-MDP CR higher than 10, not overlapping the GI tract, are generally visible on 223Ra images acquired at 24h after the administration, and possibly eligible for dosimetric studies.