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.

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.

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.

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.

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.

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.

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.

New devices for imaging in nuclear medicine.

Pinhole gamma camera imaging offers the ability to obtain high resolution images from single gamma ray emitting radiotracers playing a reasonable tradeoff between very small field of view (FoV) and sensitivity. On the other hand the total spatial resolution of a pinhole imaging device is predominantly affected by the detector intrinsic spatial resolution for reduced magnification factors. To design very compact pinhole SPET scanners with very high intrinsic spatial resolution, authors investigated a miniature gamma camera based on the newly developed Hamamatsu H8500 flat panel photomultiplier. The PSPMT was coupled to the following scintillation arrays: CsI(Tl) array with 0.2-mm, 1-mm, 1.4-mm pixel size and NaI (Tl) with 1-mm pixel size. The imaging performances were evaluated by 57Co spot and flood irradiations. NaI(Tl) array shows a better pixel identification for 1 mm pixel size, proving to be a good candidate to make a large area photodetector based on multi PSPMTs closely packed. Although CsI(Tl) array had the smallest pixel size, the low light output limited the best intrinsic spatial resolution to about 0.5 mm.