Viviana Frantellizzi

Prostate-Specific Antigen Flare Phenomenon During 223Ra-Dichloride Treatment for Bone Metastatic Castration-Resistant Prostate Cancer: A Case Report

Clinical Practice Points Ra-dichloride is an alpha-emitting radionuclide recently approved for treatment of castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. In this specific therapeutic setting, prostate-specific antigen (PSA) is not an objective biomarker in assessing Ra efficacy. We present a 79-year-old patient who was affected by CRPC and symptomatic bone metastases enrolled in the Ra-dichloride Early Access Program who presented a relevant rise in PSA levels after the fifth Ra administration. No radiological signs of disease progression were found, so this event was recognized as a PSA flare phenomenon and the last Ra infusion was administered. In clinical practice, PSA flare in the course of Ra treatment can be misinterpreted as a therapeutic failure with early withdrawal from a potentially effective therapy. During Ra treatment, PSA flare can be explained as a direct consequence of Ra cytotoxic effect on cancer cells. Further analysis should be conducted on large cohort to evaluate the clinical significance of PSA flare phenomenon during Ra treatment.

99mTc-labeled White Blood Cell Scan as a Guide to Open Biopsy in the Management of Hip and Knee Prosthesis Infection: Preliminary Results

OBJECTIVE The aim of the present prospective study was to evaluate the usefulness of labeled leukocyte scan as a guide to open biopsy for the management of hip and knee prosthesis infection in patients without loosening of orthopedic device. METHODS Twenty-six patients with suspected hip (24) and knee (2) prosthesis infection underwent routine analysis of blood, plain radiography and 99mTc-HMPAO labelled leukocyte scan (WBCS). On these basis, patients were subdivided in the following groups: bone infection without loosening (n°=14), septic loosening (n°=8), superficial infection (n°=2), no infection (n°=2). Patients with septic loosening underwent empirical antibiotic therapy in order to avoid two-stage reimplantation. When the medical treatment was effective patients were submitted to one-stage operation. Patients without loosening of prosthesis but positive WBCS results underwent open biopsy: bone samples and periprosthetic tissues were taken from the regions showing pathological leukocyte uptake at the scan. Samples were submitted to microbiological examination and antibiotic treatments were undertaken in cases of bacterial growth. A 24-months clinical and instrumental follow-up was carried out in all patients. RESULTS WBCS showed 22 patients affected by bone infection, 2 by superficial infection and 2 not infected. Height out of the 22 patients affected by deep infection had a septic loosening. In these cases, the medical treatment was inadequate in 6 patients and effective in 2. Fourteen patients with bone infection without loosening were submitted to open biopsy: in 9 cases a complete remission of the disease was found. Two patients, without infection, underwent single-stage surgery for mechanical problems. Superficial infection was assessed and successfully treated in 2 patients. CONCLUSION The obtained results indicate that a multidisciplinary approach to infection of orthopedic prostheses, characterized by the combined use of open biopsy, WBC, and microbiological examination, produced positive outcome in 9 out of 14 patients.

Role of cardiac 123I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD

BackgroundDespite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients.Methods170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy.ResultsDuring a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. 123I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between 123I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate 123I-mIBG abnormalities tended to be at higher risk of events.ConclusionAlthough SPECT 123I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between 123I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

Comparison of the imaging performances for recently developed monolithic scintillators: CRY018 and CRY019 for dual isotope gamma ray imaging applications

The growing interest for new scintillation crystals with outstanding imaging performances (i.e. resolution and efficiency) has suggested the study of recently discovered scintillators named CRY018 and CRY019. The crystals under investigation are monolithic and have shown enhanced characteristics both for gamma ray spectrometry and for Nuclear Medicine imaging applications such as the dual isotope imaging. Moreover, the non-hygroscopic nature and the absence of afterglow make these scintillators even more attractive for the potential improvement in a wide range of applications. These scintillation crystals show a high energy resolution in the energy range involved in Nuclear Medicine, allowing the discrimination between very close energy values. Moreover, in order to prove their suitability of being powerful imaging systems, the imaging performances like the position linearity and the intrinsic spatial resolution have been evaluated obtaining satisfactory results thanks to the implementation of an optimized algorithm for the images reconstruction.

Narrative medicine in metastatic prostate cancer reveals ways to improve patient awareness & quality of care

AIM To describe the journey of patients with metastatic castration-resistant prostate cancer (mCRPC) in treatment with radium-223. METHODS A multiperspective analysis was performed using narrative medicine in four Italian centers. RESULTS The substantial impact of mCRPC on quality of life through all phases of the disease was described. After an initial lack of awareness of the disease or denial of its effects, symptoms of pain, fatigue and side effects often led to sadness, fear and loneliness. The majority underwent radium-223 therapy positively, restoring their quality of life and routine activities. CONCLUSION Using narrative medicine, the importance of a patient-centered approach in the pathway of care for patients with mCRPC through all the stages of the disease was highlighted.

Aripiprazole-Triggered Alice in Wonderland Syndrome Episodes Studied with 99mTc-HMPAO Brain SPECT

A 47-years-old right-handed woman, with a history of migraine and major depression treated with aripiprazole, reported a change in her aura with the appearance of mosaic vision and left-side macrosomatognosia (Fig. 1). These body misperceptions, known as Alice in Wonderland Syndrome (AIWS), were correlated to aripiprazole intake after autonomous discontinuation and followed by migraine. Interestingly, among the causes of AIWS, there are both migraine and some drugs [1–2], but this is the first case of AIWS attributable to an antipsychotic.

223 Ra-dichloride therapy in an elderly bone metastatic castration-resistant prostate cancer patient: a case report presentation and comparison with existing literature

disability, leading to a reduced quality of life. Moreover, bone metastases in patients with CRPC are independently associated with increased mortality. In consideration of the needs of older patient population, the optimal approach of elderly PC patients poses a particular clinical challenge. Over last years, several novel drugs for CRPC have been introduced, such as the new taxan agent cabazitaxel, immunotherapy (sipuleucel-T), RANK-L inhibitor denosumab, androgen biosynthesis inhibitors (abiraterone acetate), and androgen receptor antagonists (enzalutamide). These antitumoral agents have changed therapeutic management of CRPC patients, although there is still the need to define an appropriate sequencing for their application to maximize patient benefit and minimize costs. In this evolving scenario, a first-in-class alpha-emitting radionuclide, 223Radichloride, has been recently approved for the treatment of CRPC patients with symptomatic bone metastases and no known visceral disease. FDA approval of 223Ra came in May 2013 as a result of the findings of the international, randomized, double-blind alpharadin in symptomatic prostate cancer (ALSYMPCA) Phase III trial that evaluated efficacy on overall survival of 223Ra treatment versus placebo in patients with mCRPC [2]. Thanks to its analogy to calcium, 223Ra targets areas of high osteoblastic activity such as sites of bone metastases, delivering high-energy short-range alpha particle radiation. Alpha particles are characterized by a high-linear energy transfer (LET) to surrounding tissues delivered in a short path (<100 μm), inducing double-stranded breaks in DNA with a local cytotoxic effect that is, notably, independent from dose rate, oxygen level, and cell cycle status [3]. The short penetration range of alpha particles (approximately corresponding to 2–10 cell diameters) determines a low dose of radiation delivered to normal bone-marrow cell population, with minimal hematological adverse effects. Results

Ra-223 dichloride management in a Nuclear Medicine Unit: experience of a referral institution

Prostate cancer is the most common male cancer and one of the leading causes of cancer-related morbidity and death [1]. In prostate cancer natural history, approximately 10% of patients will develop a castration-resistant disease, with a median survival of 2 years [2]. The majority of patients with metastatic CastrationResistant Prostate Cancer (mCRPC) has a radiological evidence of bone metastases, which are the main cause of pain and disability, leading to a reduced quality of life. Moreover, in patients with mCRPC bone metastases are independently associated to mortality [3].

Innovative LuYAP:Ce array for PET imaging

We present an imaging characterization of a 10 × 10 LuYAP array (2 × 2 × 10 mm3 pixels) with an innovative dielectric coating insulation (0.015 mm thick), in view of its possible use in a gamma camera for imaging positron emission tomography (PET) or in similar applications, e.g. as γ -prompt detector in hadron therapy. The particular assembly of this array was realized in order to obtain a packing fraction of 98%, improving detection efficiency and light collection. For imaging purpose, the array has been coupled with a selected Hamamatsu H10966-100 Multi Anode Photomultiplier read out by a customized 64 independent channels electronics. This tube presents a superbialkali photocathode with 38% of quantum efficiency, permitting to enhance energy resolution and consequently image quality. A pixel identification of about 0.5 mm at 662 keV was obtained, highlighting the potentiality of this detector in PET applications.

Locally vascularized pelvic accessory spleen

Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.RiassuntoIl polisplenismo e la milza accessoria sono anomalie congenite generalmente asintomatiche. Riportiamo un raro caso di polisplenismo con milza pelvica ectopica in una donna bianca di 67 anni. Nella pelvi di sinistra all’ecografia transvaginale è stata ritrovata una massa soffice, ben definita, omogenea e vascolarizzata. La paziente è stata quindi sottoposta a valutazione con RM e TC addominale con contrasto: sono state ottenute immagini con aspetto parenchimale simile alla milza. E’ stata eseguita una scintigrafia addominale con albumina umana colloidale radiomarcata con tecnezio sulla regione pelvica con scansioni planari e SPECT. I risultati hanno mostrato la presenza di un’area di captazione del radiofarmaco nella pelvi, mentre la milza è stata normalmente visualizzata. Questi ritrovamenti hanno confermato la presenza di una milza accessoria con una arteria originante dall’aorta ed una vena che si anastomizzava con la vena mesenterica superiore. Alla nostra conoscenza, nella letteratura, esiste solo un caso di vera milza ectopica localmente vascolarizzata nella pelvi.