Medical Imaging of Inflammations and Infections of Breast Implants.

Breast implants are widely used for reconstructive and/or cosmetic purposes. Inflammations and infections of breast implants represent important complications in clinical practice. The proper management of complications is necessary: diagnostic imaging plays a key role in detecting sites of inflammation and/or infection. The present review aims to illustrate the radiological findings of these conditions with different imaging techniques, such as mammography (MX), ultrasound (US), magnetic resonance imaging (MRI), and nuclear medicine imaging. A knowledge of these findings is essential for radiologists and nuclear medicine physicians to provide helpful information for the clinical management of these complications.

HMGB1 expression in leukocytes as a biomarker of cellular damage induced by [99mTc]Tc-HMPAO-labelling procedure: A quality control study.

PURPOSE: Autologous White Blood Cells (WBC) scintigraphy is based on a multi-step sequence of cell separation and radiolabelling. Besides in vivo imaging quality control, no molecular tool is available to evaluate WBC damage secondary to cell manipulation. High Mobility Group Box 1 (HMGB1) is a protein of the alarmins family, secreted by innate immune cells and released from the nucleus of damaged cells following different types of injury. Aim of this study was to evaluate HMGB1 levels in WBC cytosolic extracts (CE) before and after [99mTc]Tc-HMPAO labelling procedure, as a biomarker of induced WBC damage. PROCEDURES: Patients with suspect of prosthetic joint infection were prospectively enrolled. HMGB1 levels were evaluated by immunoblotting analysis in plasma (t0), and in WBC-CE before (t1) and after (t2) [99mTc]Tc-HMPAO labelling. Blood samples from healthy subjects were evaluated under the same procedure. RESULTS: Twenty consecutive patients referred for WBC scintigraphy and ten controls were enrolled. HMGB1 levels were significantly upregulated both in plasma (t0) and in circulating WBC-CE (t1) from patients compared to controls (p < 0.0001). Otherwise, WBC-CE from [99mTc]Tc-HMPAO-labelled leukocyte concentrate (t2) did not show significant changes in HMGB1 levels compared to the cold leukocyte sample (t1). CONCLUSIONS: The evaluation of HMGB1 levels in WBC-CE from each subject after radiolabelling with [99mTc]Tc-HMPAO did not show significant changes compared to the cold cellular sample. These results further prove the reliability of [99mTc]Tc-HMPAO leukocyte radiolabelling procedure in terms of cell viability and suggest that the monitoring of this alarmin may represent a specific tool to evaluate a secondary damage of WBC induced by radiolabelling procedure. In addition, significant upregulation of HMGB1 levels was found in WBC-CE and in plasma from patients with suspect of PJI - compared to healthy donors - reasonably related to their underlying inflammatory/infective condition.

Functional lung volume mapping with perfusion Single-Photon Emission Computed Tomography scan for radiotherapy planning in patients with locally advanced nonsmall cell lung cancer.

OBJECTIVES: Radical chemotherapy-radiotherapy represents the standard treatment for locally-advanced nonsmall cell lung cancer (NSCLC). Conventional radiotherapy achieves limited local tumor control, but dose escalation to the primary tumor is prevented by radiotherapy-induced toxicity. The aim of this study was to evaluate feasibility of tailored intensity-modulated radiotherapy (IMRT) planning based on lung single-photon emission computed tomography (SPECT) perfusion data and to compare functional and conventional dose-volume parameters. METHODS: A total of 21 patients were prospectively enrolled. Patients underwent IMRT treatment with 2 Gy/fraction (median total dose of 60 Gy). Lung perfusion SPECT images were acquired before radiotherapy and 3 and 6 months after radiotherapy completion. SPECT and planning computed tomography images were co-registered using MIM-MAESTRO software with 3D-PET Edge algorithm. Lung volumes were defined anatomically as total lung and functionally as total not functional lung and total functional lung. Dose-volume histograms were calculated using QUANTEC constraints [mean lung dose (MLD)<20 Gy, V20<20%]. For each patient, conventional and functional radiotherapy plans were generated and compared. RESULTS: A total of 19 of 21 patients with NSCLC were included (mean age 66 years, 11 stage IIIA, 8 stage IIIB), 12/19 patients completed the 6-months follow-up. A significant reduction of mean V20 was observed in functional radiotherapy planning compared to conventional plan (405.9 cc, P < 0.001). Mean MLD was also lower in the SPECT-based plans, but the difference was not statistically relevant (0.8 Gy, P = 0.299). G2 radiation pneumonitis was observed in two patients. CONCLUSIONS: Functional radiotherapy planning allowed to decrease functional lung irradiation compared to conventional planning. The possibility to limit radiotherapy-induced toxicity could allow us to perform an effective dose-escalation to target volume.

In Vivo Microbial Targeting of 99mTc-Labeled Human ß-Defensin-3 in a Rat Model of Infection.

OBJECTIVE: Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, Ga-citrate, labeled immunoglobulin G, F-FDG) is capable of this differentiation, producing a nonnegligible false-positive rate. Recently, our group reported on a reliable labeling procedure of the antimicrobial peptide human ß-defensin 3 (HBD-3) with Tc. The aim of this study was to evaluate in vivo Tc-HBD-3 uptake in a rat model of infection. METHODS: Recombinant HBD-3 was radiolabeled with Tc. Radiolabeling yield and specific activity of the compound were calculated. Chromatographic behavior and biological activity of Tc-HBD-3 were also assessed. An experimental model involving Staphylococcus aureus-induced infection and carrageenan-induced aseptic inflammation was performed in 5 Wistar rats. Serial planar scintigraphic acquisitions were performed from 15 to 180 minutes after Tc-HBD-3 intravenous administration. Radiotracer uptake was evaluated qualitatively and semiquantitatively as a target-to-nontarget ratio. RESULTS: Radiolabeling yield of Tc-HBD-3 was 70% with a specific activity of 6 to 8 MBq/µg. A significant and progressive Tc-HBD-3 uptake was observed in the site of S. aureus-induced infection, with a maximum average target-to-nontarget ratio of 5.7-fold higher in the infection site compared with an inflammation site observed at 140 minutes. CONCLUSIONS: In vivo imaging with Tc-HBD-3 in a rat model of S. aureus-induced infection demonstrated favorable uptake in the infection site compared with sterile inflammation and background. These promising results, together with previous ex vivo uptake and toxicity assessment, suggest the potential of Tc-HBD-3 as a novel agent for specific infection imaging.

Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: Report of technical procedural standards from an Italian Nuclear Medicine expert panel. / Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano.

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots. 2-3 subcutaneous injections should be performed (II-III±I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology.

No evidence of association between psychological distress and pain relief in patients with bone metastases from castration-resistant prostate cancer treated with 223Radium.

OBJECTIVE: Painful bone metastases cause reduced quality of life (QoL) in patients with castration-resistant prostate cancer (CRPC). Alpha-emitter 223Radium is associated with a clear survival benefit and significant bone pain palliation in CRPC patients with symptomatic bone metastases. The aim of this study was to evaluate the association between pain relief and psychological distress during the time course of therapy in patients treated with 223Radium. METHODS: A total of 63 patients with mCRPC undergoing 223Radium treatment in our Nuclear Medicine Unit, carefully instructed on the possibility of improving the pain and increasing the survival by the treatment, were retrospectively evaluated. Pain response during treatment was assessed with the Brief Pain Inventory Numeric Rating Scale. Psychological distress was evaluated through the analysis of specific items from EORTC QoL questionnaires C30 and BM22, submitted to patients at baseline and after each 223Radium cycle. RESULTS: Pain intensity showed a significant decrease after first 223Radium administration (-1.03 points, p = 0.0032), with a subsequent stability through the course of treatment (-1.30 points, p = <0.001). Psychological status did not show significant variations during 223Radium treatment, and no association was found between psychological status and pain relief in our population. CONCLUSIONS: In our experience, bone pain palliation provided by 223Radium do not correlate with an improved psychological status in patients with advanced PC. This observation emphasises the role of the psychological aspect in the evaluation of the QoL and the necessity of a multidisciplinary approach in which the emotional aspect of the patient is carefully evaluated.

Safety and Efficacy of Combined Peptide Receptor Radionuclide Therapy and Liver Selective Internal Radiation Therapy in a Patient With Metastatic Neuroendocrine Tumor.

Nuclear medicine treatments of well-differentiated neuroendocrine tumors (NETs) are gaining increasing acceptance among clinicians. Peptide receptor radionuclide therapy (PRRT) is an effective systemic treatment, providing a significant survival benefit and improving patients' quality of life. Locoregional selective internal radiation therapy (SIRT) is a safe and effective treatment for unresectable NET liver metastases, providing good local tumor control and symptomatic relief. Few reports in literature examine the sequential use of PRRT and SIRT in metastatic NET. We report the case of a metastatic NET patient treated with sequential PRRT-SIRT achieving a long disease control interval without cumulative toxicity issues.

Radium-223 in patients with metastatic castration-resistant prostate cancer: Efficacy and safety in clinical practice.

Radium-223 has improved overall survival (OS) and reduced symptomatic skeletal events (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases (ALSYMPCA trial). Our aim was to assess clinical and biochemical factors related to survival, safety and survival outcomes of Radium-223 in a clinical practice setting. We retrospectively analysed 32 mCRPC patients treated with Radium-223, assessing bone scan, pain reduction, alkaline phosphatase (ALP) and prostate-specific antigen (PSA) response (≥30% reduction). At scintigraphic assessment, 41% had partial response with a disease control rate of 91%; 56% had ALP response and 25% had PSA response; 41% had pain reduction with pain control of 72%. Scintigraphic response and stability were correlated with longer median progression-free survival (mPFS) (13 and 12 vs. 6 months; P=0.002) and mOS (16 and 12 vs. 6 months; P=0.003). ALP response was associated with longer mPFS (13 vs. 12 months; P=0.2) and mOS (16 vs. 12 months; P=0.2). PSA response was associated with longer mPFS (13 vs. 12 months; P=0.02), whereas mOS could not be computed. Pain response and stability were associated with survival benefit according to mPFS (13 and 12 vs. 9 months) and mOS (both 16 vs. 12 months) without statistical significance. Baseline ALP <220 UI/l, Eastern Cooperative Oncology Group (ECOG) performance status 0 and absence of previous chemotherapy correlated with statistically significantly longer survival outcomes. Skeletal-related events (SRE) occurred in three patients and median time to first SRE was 9.5 months, mPFS was 12 months and mOS 14 months. G3-G4 toxicities developed in 16% of patients. Our results are in line with those reported in the pivotal trial and in other retrospective studies. In conclusion, Radium-223 was associated with high scintigraphic, biochemical and pain response rates and was tolerated well by most patients. Response to Radium-223 and better baseline factors correlated to longer survival in clinical practice experience as in the clinical trial setting.

Radiopharmaceuticals Labelled with Copper Radionuclides: Clinical Results in Human Beings.

BACKGROUND: Positron emission tomography (PET) is an instrumental diagnostic modality developed around the positron-emitting radioisotopes of biologically important elements such as carbon, oxygen and nitrogen (11C, 15O, 13N). Among longer-lived PET radionuclides, 18F is by far the most commonly used radiotracer, extensively used for tumour imaging with FDG ([18F]-fluorodeoxyglucose) and also frequently investigated in the development of novel radiopharmaceuticals. Many other positron- emitting radionuclides with higher atomic numbers and longer half-lives have been investigated for both imaging and therapeutic purposes, including the halogens (124I, 120I, 76Br) and a number of metal radionuclides. The radio-copper has attracted considerable attention, because they include isotopes which, due to their emission properties, offer themselves as agents of both diagnostic imaging (60Cu, 61Cu, 62Cu, 64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu). OBJECTIVES: Although the use of this radionuclide has grown exponentially over the last decade, academic institutions have largely been responsible for its production and for the development of the vast majority of radiopharmaceutical based on these nuclides. A number of compounds labelled with Cuisotopes have been proposed, not only for imaging purposes but also for therapy. The aim of the present paper is to provide an overview on the clinical results obtained in human beings with copper radionuclides. CONCLUSION: Several preliminary studies and clinical trials evaluated the potential clinical role of copper radioisotopes for diagnostic and therapeutic purposes. 64Cu seems to be the most suitable radioisotope for future clinical applications due to its longer half-life (12.7 h) and its commercial availability. Future clinical applications of copper radioisotopes could be enhanced by the possibility of radioligand therapy with the beta-emitting 67Cu, creating a new "theranostics pair".

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.

Radio-localization of Non-Palpable Breast Lesions Under Ultrasonographic Guidance: Current Status and Future Perspectives.

BACKGROUND: Due to the spread of mammographic screening programs, a constant increase of clinically-occult breast cancer diagnosis has been registered. A correct approach to nonpalpable breast lesions requires an accurate intra-operative localization in order to achieve a complete surgical resection. The aim of this paper is to describe the state of the art of the US-guided procedures such as Radio-guided Occult Lesion Localization (ROLL) and Radio-guided Seed Localization (RSL) in comparison to the most widely adopted Wire-Guided Localization (WGL). METHODS: Links to full text papers and abstracts published in the last 25 years regarding localization of non-palpable breast lesions were researched using PubMed service of US National Library of Medicine. Using the term "non-palpable breast lesions localization", different localization techniques were considered and analyzed. Human studies, published in English, French, German, Italian, and Spanish in journals with an impact factor index, were taken into account, independently of the type of article (clinical trial, review, editorial, etc.) or radiopharmaceutical used. Since the aim was to assess the clinical value of the procedures, a higher relevance was assigned to studies with significantly high number of patients and to those comparing at least two localization techniques. The reliability of each technique was evaluated taking into account several parameters such as correlation index between two localization procedures, risk of complications, lesion margin involvement and rate re-operation. CONCLUSIONS: Since their introduction in clinical practice, several randomized clinical trials and meta-analyses showed the accuracy and reliability of radio-guided procedures performed under ultrasonographic guidance. ROLL and RSL offer a practical approach to the management of clinically-occult breast lesions.

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.

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.

A modified sentinel node and occult lesion localization (SNOLL) technique in non-palpable breast cancer: a pilot study.

BACKGROUND: The spread of mammographic screening programs has allowed an increasing amount of early breast cancer diagnosis. A modern approach to non-palpable breast lesions requires an accurate intraoperative localization, in order to achieve a complete surgical resection. In addiction, the assessment of lymph node status is mandatory as it represents a major prognostic factor in these patients. The aim of this study is to evaluate the reliability of a modified technical approach using a single nanocolloidal radiotracer to localize both sentinel node and breast occult lesion. METHODS: Twenty-five patients with a single non-palpable breast lesions and clinically negative axilla were enrolled. In the same day of surgery, patients underwent intratumoral and peritumoral administration of (99m)Tc-labeled nanocolloid tracer under sonographic guidance. A lymphoscintigraphy was performed to localize the sentinel lymph node and its cutaneous projection was marked on the skin in order to guide the surgeon to an optimal incision. During surgery an hand-held gamma-detection probe was used to select the best surgical access route and to guide localization of both occult breast lesion and sentinel lymph node. After specimen excision, the surgical field was checked with the gamma-probe to verify the absence of residual sources of significant radioactivity, thereby ensuring a radical treatment in a single surgical session and minimizing normal tissue excision. RESULTS: Both targeted breast lesion and sentinel lymph node were localized and removed at the first attempt in every patients and histopathological diagnosis of malignancy was confirmed in 25/26 samples. Non-palpable lesions were included within the surgical margins in all patients and in all samples surgical margins were free from neoplastic infiltration thus avoiding any further reintervention. Only two patients showed metastatic involvement of sentinel lymph node. CONCLUSIONS: The modified sentinel node and occult lesion localization (SNOLL) technique performed with a single injection of nanocolloidal radiotracer has shown an excellent intraoperative identification rate of both non-palpable lesion and sentinel lymph node. This procedure offers, as opposed to standard techniques, an accurate, simple and reliable approach to the management of non-palpable breast cancer.