Erika De Lucia

Bio: Erika De Lucia is an academic researcher. The author has contributed to research in topics: Bragg peak & Charged particle. The author has an hindex of 7, co-authored 11 publications receiving 186 citations.

Toward Radioguided Surgery with β− Decays: Uptake of a Somatostatin Analogue, DOTATOC, in Meningioma and High-Grade Glioma

Abstract: A novel radioguided surgery (RGS) technique for cerebral tumors using β− radiation is being developed. Checking for a radiotracer that can deliver a β− emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of 90Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β− probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Methods: Uptake and background from healthy tissues were estimated on 68Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. Results: All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% false-positive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2–0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Conclusion: Uptake of 90Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the β− probe.

Secondary radiation measurements for particle therapy applications: prompt photons produced by $^{4}$He, $^{12}$C and $^{16}$O ion beams in a PMMA target

Abstract: Charged particle beams are used in Particle Therapy (PT) to treat oncological patients due to their selective dose deposition in tissues and to their high biological effect in killing cancer cells with respect to photons and electrons used in conventional radiotherapy. Nowadays, protons and carbon ions are used in PT clinical routine but, recently, the interest on the potential application of helium and oxygen beams is growing due to their reduced multiple scattering inside the body and increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands for online dose monitoring techniques, crucial to improve the quality assurance of treatments. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Prompt photons are produced by nuclear de-excitation processes and, at present, different dose monitoring and beam range verification techniques based on the prompt {\gamma} detection have been proposed. It is hence of importance to perform the {\gamma} yield measurement in therapeutical-like conditions. In this paper we report the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a PMMA target. The measurements were performed at the Heidelberg Ion-beam Therapy center (HIT) with beams of different energies. A LYSO scintillator has been used as photon detector. The obtained {\gamma} yields for $^{12}$C ion beams are compared with results from literature, while no other results from $^{4}$He and $^{16}$O beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-{\gamma} based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Time Evolution of DOTATOC Uptake in Neuroendocrine Tumors in View of a Possible Application of Radioguided Surgery with β− Decay

Abstract: A novel radioguided surgery (RGS) technique exploiting β− radiation has been proposed. To develop such a technique, a suitable radiotracer able to deliver a β− emitter to the tumor has to be identified. A first candidate is represented by 90Y-labeled DOTATOC, a compound commonly used today for peptide radioreceptor therapy. The application of this β− RGS to neuroendocrine tumors (NET) requires study of the uptake of DOTATOC and its time evolution both in tumors and in healthy organs and evaluation of the corresponding performance of the technique. Methods: Uptake by lesions and healthy organs (kidneys, spleen, liver and healthy muscle) was estimated on 177Lu-DOTATOC SPECT/CT scans of 15 patients affected by NET with different localizations, treated at IRCCS–Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. For each patient, SPECT/CT images, acquired at 0.5, 4, 20, 40, and 70 h after injection, were studied. For each lesion, the tumor-to-nontumor ratio (TNR) with respect to all healthy organs and its time evolution were studied. A subset of patients showing hepatic lesions was selected, and the TNR with respect to the nearby healthy tissue was calculated. By means of a Monte Carlo simulation of the probe for β− RGS, the activity that is to be administered for a successful detection was estimated lesion-by-lesion. Results: Uptake of DOTATOC on NETs maximized at about 24 h after injection. The cases of hepatic lesions showed a TNR with respect to the tumor margins compatible with the application of β− RGS. In particular, 0.1-mL residuals are expected to be detectable within 1 s with 5% false-negative and 1% false-positive by administering the patient as little as 1 MBq/kg. Conclusion: The balance between tumor uptake and metabolic washout in healthy tissue causes the TNR to increase with time, reaching its maximum after 24 h, and this characteristic can be exploited when a radiotracer with a long half-life, such as 90Y, is used. In particular, if 90Y-DOTATOC is used with liver NET metastases, the proposed RGS technique is believed to be feasible by injecting an activity that is one third of that commonly used for PET imaging.

Monitoring of Hadrontherapy Treatments by Means of Charged Particle Detection

Abstract: The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. Charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in hadrontherapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). An important outcome of these studies is that the experimental single track resolution needed for charged particle based monitoring applications can be safely of the order of few millimeters, without spoiling the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.

EANO guidelines for the diagnosis and treatment of meningiomas

Abstract: Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

Prompt-gamma monitoring in hadrontherapy: A review

Abstract: Secondary radiation emission induced by nuclear reactions is correlated to the path of ions in matter. Therefore, such penetrating radiation can be used for in vivo control of hadrontherapy treatments, for which the primary beam is absorbed inside the patient. Among secondary radiations, prompt-gamma rays were proposed for real-time verification of ion range. Such a verification is a desired condition to reduce uncertainties in treatment planning. For more than a decade, efforts have been undertaken worldwide to promote prompt-gamma-based devices to be used in clinical conditions. Dedicated cameras are necessary to overcome the challenges of a broad- and high-energy distribution, a large background, high instantaneous count rates, and compatibility constraints with patient irradiation. Several types of prompt-gamma imaging devices have been proposed, that are either physically-collimated or electronically collimated (Compton cameras). Clinical tests are now undergoing. Meanwhile, other methods than direct prompt-gamma imaging were proposed, that are based on specific counting using either time-of-flight or photon energy measurements. In the present article, we make a review and discuss the state of the art for all techniques using prompt-gamma detection to improve the quality assurance in hadrontherapy.

Improved Detection of Transosseous Meningiomas Using 68Ga-DOTATATE PET/CT Compared with Contrast-Enhanced MRI.

Abstract: 68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin receptor 2 expression. Transosseous extension of intracranial meningiomas is known to be an important risk factor for tumor recurrence and patient mortality. We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast-enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative and quantitative imaging parameters. Methods: In this institutional review board-approved retrospective study, subjects were selected from 327 consecutive 68Ga-DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma. Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma diagnosis with inclusion or exclusion of transosseous extension as the standard of reference. Imaging was analyzed by two readers. Tracer uptake values and meningioma volumes were determined. χ2, Mann-Whitney U, Wilcoxon signed rank, and McNemar tests, as well as receiver-operating-characteristic analyses, were performed to compare variables and diagnostic performance. Results: Eighty-two patients fulfilled the inclusion criteria. Patients with transosseous extension of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3 mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2 vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga-DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5% vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection of osseous involvement (P < 0.001). In receiver-operating-characteristic analysis, PET/CT assessment performed better than CE-MRI (area under the curve, 0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable results for extraosseous meningiomas (P = 0.132) and the extraosseous part of transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga-DOTATATE PET/CT enables improved detection of the transosseous extension of intracranial meningiomas compared with CE-MRI.

Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics.

Abstract: The differential diagnosis between meningioma and others tumors can be challenging. This study aimed to evaluate different immunohistochemical markers for the differential diagnosis between meningioma and their morphological mimics. Immunohistochemistry was performed on tissue microarray with antiepithelial membrane antigen (EMA), progesterone receptor, somatostatin receptor 2A (SSTR2A), CD34, STAT6, S100, SOX10, HMB45, MelanA, GFAP, inhibin, and BCL2 antibodies. One hundred and twenty-seven meningiomas, 26 solitary fibrous tumor/hemangiopericytomas (SFT/HPC), 39 schwannomas, 17 hemangioblastomas, 21 melanomas, 9 gliosarcomas, 5 neurofibromas, 9 peripheral primitive neuroectodermal tumors, 7 synovial sarcomas, and 5 malignant peripheral nerve sheath tumors were included in the microarray. SSTR2A was the most sensitive (95.2%) and specific (92%) marker of meningiomas. In combination, SSTR2A and/or EMA positivity reached maximal sensitivity (100%). Coexpression of SSTR2A and EMA was the most specific (94.8%) for the diagnosis of meningioma, regardless of the grade or subtype, with the exception of the differential diagnosis with synovial sarcoma. All synovial sarcomas were EMA-positive and 6/7 SSTR2A-positive. STAT6 showed optimum sensitivity and specificity (100%) for SFT/HPC. SOX10 was the most sensitive (94.3%) and specific (100%) marker to discriminate meningiomas from schwannomas. In conclusion, SSTR2A, STAT6, and SOX10 were the most sensitive and specific markers to distinguish meningiomas from their morphological mimics.

Recent advances in nuclear and hybrid detection modalities for image-guided surgery.

Abstract: Introduction: Radioguided surgery is an ever-evolving part of nuclear medicine. In fact, this nuclear medicine sub-discipline actively bridges non-invasive molecular imaging with surgical care. Nex...