A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience.

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.

Computerized tomography texture analysis of pheochromocytoma: relationship with hormonal and histopathological data.

OBJECTIVES: Pheochromocytomas are rare tumors which can present with heterogeneous secretion profiles, clinical manifestations, and radiologic appearance. Under a histopathological point of view, they can be characterized as more or less aggressive with the Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) score. The aim of this study is to analyze the texture analysis characteristics of pheochromocytoma and identify whether the texture analysis can yield information aiding in the diagnosis and the characterization of those tumors. METHODS: Radiological, biochemical, and histopathological data regarding 30 consecutive patients with histologically confirmed pheochromocytoma were analyzed. Images obtained in the unenhanced, late arterial, venous, and delayed phases were used for the texture analysis. RESULTS: Urinary epinephrine and metanephrine levels showed a significant correlation (R2 = 0.946; R2 = 699) in the multivariate linear model with texture features, as well as Ki-67 (R2 = 0.397), PASS score (R2 = 0.182), GAPP score (R2 = 0.705), and cellularity showed a significant correlation (R2 = 0.389). The cluster analysis based on radiomic features resulted in 2 clusters, with significative differences in terms of systolic and diastolic blood pressure values at the time of diagnosis (p = 0.025), GAPP score (4 vs 6, p = 0.05), histological pattern (1-2, p = 0.039), and comedonecrosis (0% vs 50%, p = 0.013). CONCLUSION: In conclusion, our study provides the proof of concept for the use of texture analysis on contrast-enhanced CT images as a noninvasive, quantitative tool for helping in the characterization of the clinical, biochemical, and histopathological features of pheochromocytoma.

Radiologically defined lipid-poor adrenal adenomas: histopathological characteristics.

BACKGROUND: Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA. METHODS: Patients with LPA (n = 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (n = 17), Weiss score and Lin-Weiss-Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated. RESULTS: Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (n = 6) and those with adrenal incidentalomas associated with primary aldosteronism (n = 2), autonomous cortisol secretion (n = 14), or non-functioning (n = 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2 vs 17.3 ± 8.4 mm, P < 0.001), higher CT unenhanced density (29.1 ± 11.0 vs 23.1 ± 9.0 HU, P = 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4 vs 4.4 ± 2.3 SUV, P = 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin-Weiss-Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors. CONCLUSIONS: Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.

Carbon ions therapy as single treatment in chordoma of the sacrum. Histologic and metabolic outcome studies.

OBJECTIVE: Even though carbon ions treatment (CIRT) of sacral chordoma (SC) substantially reduces tumor mass, tumor remnants are observed in most patients. Differentiating tumor remnants from necrosis is challenging, expensive in terms of imaging and time-consuming. So far, there has not been a systematic histological and metabolic analysis of post-CIRT lesions. We designed a prospective study aiming to histologically a metabolically differentiate between viable tumor and foci of necrosis and of fibrosclerosis after CIRT and correlate these findings to clinical outcome in patients with SC. PATIENTS AND METHODS: Between January 2013 and December 2016 18 patients, 12 males and 6 females, with histological confirmation of sacral chordoma, underwent CIRT. The total dose was 70.4 GyE, with a daily fraction of 4.4 GyE, for 4 weeks. MRI was performed every three months after treatment. FDG PET-CT scan and CT-guided needle biopsy were performed 6-12 months after CIRT. The incidence of complications (intraoperative and postoperative), local control (LC), overall survival (OS) and progression-free survival (PFS), changes in neurological status, clinical outcomes and toxicity were considered. RESULTS: All histological analysis but 2 reported signs of necrosis and of fibrosclerosis after CIRT. One of these 2 patients turned into a dedifferentiated chordoma. Radiological partial response (PR) was observed in 10 patients (56.3%) and stable disease (SD) in 5 patients (28.3). Two patients (11%) had a local relapse. The overall survival rate was 100% at 24 months. FDG PET CT after CIRT showed uptake decreasing compared with the baseline exam in all but one patient. CONCLUSIONS: The histological presence of necrosis and of fibrosclerosis after CIRT at the histological analysis supports the previous clinical evidence on the efficacy of CIRT. Volumetric stability of the residual mass should be considered as a success of treatment. In cases of a volumetric increase of the mass, a CT needle biopsy should always be performed. In our series, during the follow-up, the FDG-PET was able to promptly detect an increased uptake in the case which later was histologically defined as dedifferentiated chordoma.

Low dose radiation 18F-fluoride PET/CT in the assessment of Unilateral Condylar Hyperplasia of the mandible: preliminary results of a single centre experience.

BACKGROUND: Unilateral condylar hyperplasia (UCH) of the mandible, or Hypercondylia, is a pathological condition that determines an abnormal growth of the affected condyle.Bone SPECT with Tc99m-diphosphonates is a successful tool in the diagnosis of UCH. EANM guidelines also suggest the use of 18F-NaF PET/CT, though it leads to a higher radiation exposure. AIM: As UCH patients are young, we aimed to develop a low dose 18F-Fluoride PET/CT protocol and compare it to a standard injected activity scan, to assess if the image quality remains unchanged. MATERIALS AND METHODS: We prospectively enrolled 20 patients (7 males, 13 females, mean age 23.2) with UCH, who underwent 18F-NaF PET/CT to assess the hypercondylia. We administered a low activity of 18F-NaF (2.9 MBq/kg) in 15 patients and a standard activity (5.3 MBq/kg) in 5 patients. Activity range was chosen according to 2015 EANM guidelines.To determine if the scans with low radiotracer activity were "diagnostic" such as those with standard activity, two expert nuclear medicine physicians, unaware of the administered activity, independently reviewed the scans and expressed a final qualitative judgment in terms of "diagnostic"/"non-diagnostic" scan. Furthermore, we compared the effective dose of a low injected activity PET/CT to the standard one and to a Bone SPECT performed with standard injected activity of Tc99m-diphosphonates. RESULTS: Reviewers classified 19 of 20 scans as "diagnostic". Only one of them was classified as "non diagnostic" due to condylar arthrosis that disturbed the correct evaluation of condylar radiotracer uptake. The effective dose of a 18F-Fluoride PET/CT, in patient of 70 kg, is about 3.5 mSv in scans performed with 2.9 MBq/kg [0.017 mSv/MBq × 2.9 MBq/kg × 70 kg] and about 6.3 mSv in ones performed with 5.3 MBq/kg [0.017 mSv/MBq × 5.3 MBq/kg × 70 kg]. The effective dose of 99mTc-MDP bone SPECT is about 3.2 mSv [0.0043 mSv/MBq × 740 MBq of 99mTc-MDP]. DISCUSSION: 18F-NaF PET/CT performed with a low radiotracer activity allows a good assessment of UCH similar to that performed with an ordinary activity. The effective radiation dose of a low-injected activity PET/CT is significantly lower than an ordinary-injected activity and is not significantly higher than the most used Bone SPECT. Moreover PET/CT is performed in 1.5 h while Bone SPECT requires at least 3.5 h. CONCLUSIONS: The 18F-Fluoride PET/CT procedure could be performed with 2.9 MBq/Kg (minimum 185 MBq, recommended at least 200 MBq) of 18F-NaF to minimize the effective radiation dose received, maintaining the quality of the scan. Further studies including a larger number of patients and clinical follow-up are needed to confirm our preliminary findings.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. MATERIALS AND METHODS: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Interpretation of 11C-choline PET/CT for the diagnosis of local relapse in radically treated prostate cancer.

PURPOSE: 11C-choline PET/CT is a widely-used tool for the diagnostic of prostate cancer (PCa). In literature, a great variability of local relapse (LR) detection rate is reported. The aim of this study is to provide positivity criteria for 11C-choline PET/CT detection of LR in patients who had surgery for PCa and presented prostate specific antigen (PSA) failure. METHODS: Sixty patients radically treated for PCa and presenting PSA failure were retrospectively analysed. Two Nuclear Medicine Physicians revised the 11C-choline PET/CT scans and defined by consensus if even mild focal uptake was present in the prostate bed (PB) and bladder-urethral junction (BUJ) along midline, regardless the previous report results.The results were subsequently correlated with a clinical and radiological follow up (FU) of 1 to 2 year and with TNM staging, Gleason score (GS), PSA level at relapse, radiotherapy (RT) and hormone therapy (HT) after surgery. RESULTS: There was focal uptake in 22/60 patients; 11 of them were true positive and 11 false positive. The PSA level showed a tight connection with the true positivity/negativity of Choline scan. Most of true positive cases (10/11 patients) presented a PSA ≥ 1 ng/ml, while approximately half of the false positive cases (5/11 patients) presented PSA below 1 ng/ml. The other variables were not correlated to Choline detection rate for LR. CONCLUSIONS: This study shows that an even mild focal uptake of Choline in the PB and BUJ along midline must be considered suspicious for LR in patients radically treated for PCa, especially if they are presenting with PSA level > 1 ng/ml.

18F-FDG PET/CT scan confirmed by pathology findings in a singular case of squamous cell carcinoma of the epiglottis.

BACKGROUND: Only about 1% of all head and neck lateral or paramedian cancers described in the scientific literature shows, in staging, contralateral cervical adenopathy without ipsilateral pathological involvement of lymph nodes. CASE PRESENTATION: This case is one of them, in which 18F-FDG PET/CT scan is confirmed by pathology findings, and has correctly identified all metastatic disease foci. CONCLUSIONS: To date, PET/CT is not recommended in head and neck cancer staging. However, the use of PET/CT in head and neck cancer staging can define possible metastatic disease foci, clarify c.e. CT suspicious findings and, in some cases, change the TNM stage, with a strong prognostic and therapeutic impact.

18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease.

Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.

Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]tracers, [11C]/[18F]-HTP).

Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate.

Imaging biomarkers in prostate cancer: role of PET/CT and MRI.

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed.

Diagnostic imaging work-up for disease relapse after radical treatment for prostate cancer: how to differentiate local from systemic disease? The urologist point of view.

About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10-20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer (18)F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20-25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases.

The dilemma of localizing disease relapse after radical treatment for prostate cancer: which is the value of the actual imaging techniques?

Only few patients with PSA relapse after radical treatment will show clinically detectable disease. Although the natural history of recurrent prostate cancer is often one of the slowly progressing diseases, in some men it can be rapid and may need a salvage treatment. In general, time to PSA relapse, PSA velocity and PSA doubling time are useful in patient assesment. In patients with PCa disease relapse after primary therapy, salvage treatment for a local recurrence should only be offered to patients with little risk of already having metastases. In these patients a systemic imaging negative for metastases is mandatory, a positive biopsy is not always necessary before radiotherapy, but is mandatory before salvage prostatectomy. In patients with a high risk of distant metastases and suitable for systemic salvage therapy, a positive lesion must be obviously visualized with one of the currently available imaging techniques. Transrectal ultrasound has low accuracy in the detection of the recurrence. Multiparametric Magnetic Resonance Imaging may have a role in the early phase of PSA relapse. Conventional imaging, such as bone scan and CT, are not suggested in the initial phase of BCR. Today, it has been reported that PET/CT allows changing the therapeutic strategy (from palliative to curative treatment and vice-versa) in about 20% of cases. In recent years, the new radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. The aim of the present paper is to evaluate the management of patients with BCR after radical treatment of PCa from the urologist point of view.

Living organ donation, a therapeutic possibility, is still poorly used in Italy: a national analysis.

Validity of living donor kidney transplantation is universally accepted. In contrast, after enthusiastic adoption in the 1990s, living donor liver transplantation has decreased in recent years. The aim of the present study was to evaluate retrospectively the current use of this form of donation in Italy by comparing liver and kidney cadaveric and living donations from 2002 to 2010. The number of liver transplantations from living donors has decreased from 34 in 2002 (3.9% of total) to 13 in 2010 (1.3% of total). In contrast, kidney transplantation from living donors increased from 126 (7.9% of total) to 186 (11% of total). We observed that living donations for kidney transplantation are still underused, especially with unrelated donors. Living donor liver transplantation has decreased in recent years; this procedure should be reserved to centers with particular expertise. It would be appropriate to implement programs to increase the attention of health professionals and the general population and to integrate living donations into programs of deceased organ donation.

Contrast enhanced MRI and ¹8F-FDG PET-CT in the assessment of multiple myeloma: a comparison of results in different phases of the disease.

OBJECTIVES: The aim of our study was to compare the accuracy of contrast enhanced MRI and FDG PET-CT in the staging, treatment evaluation and follow-up of multiple myeloma. METHODS: We retrospectively reviewed 210 PET-CT and 210 MRI studies of patients affected by multiple myeloma. MRI was always performed within 15 days of PET-CT. All the images have been evaluated by two expert oncologic radiologists. RESULTS: Patient population included 81 females and 110 males (age 61.9 ± 9.9 years-old). Sixty-two patients have been evaluated at diagnosis, 58 at the end of therapies and 90 during follow-up. In 12/62 patients (19.4%) at diagnosis, differences between MRI and PET-CT findings determined changes in the staging: PET-CT was responsible for 11 down-staging (17.7%) and MRI only for one (1.6%). In 27/40 patients (67.5%) with good or complete clinical response to therapies the normalization of findings was faster for PET-CT than MRI. Ten out of 90 patients (10/90 - 11.1%) in follow-up protocol presented clinical recurrence of the disease: MRI detected active lesions in 8 of them (80.0%) and PET-CT in 5 patients (50.0%, all detected by MRI too). CONCLUSIONS: MRI achieved better results than PET-CT in the staging and in patients with multiple myeloma recurrence. PET-CT, showed prompt change of imaging findings, faster than MRI, in patients with positive response to therapy.

Biopsy for suspected spondylodiscitis.

BACKGROUND: Vertebral biopsy is fundamental in determining whether a spinal lesion is of infectious or neoplastic etiology. Accurate diagnosis is critical for proper medical and/or surgical treatment and consequently for the prognosis of the patient. CT-guided percutaneous spinal biopsy (CTSB) may minimize the risk of contamination and complications. AIM: To demonstrate the importance and efficacy of CTSB and subsequent microbiologic/histological examination in the diagnosis of spinal lesions, particularly for those of an infectious nature. MATERIALS AND METHODS: Two series of spinal infection patients. Prospective series of 69 patients (2009-2011), 24 of whom underwent CTSB. Retrospective series of 130 patients (1999-2008), 65 of whom underwent CTSB. All patients had microbiologic and histological testing of biopsy samples, when possible. RESULTS: For the 2009-2011 patient series, histological examination yielded a diagnosis in 81.8% of cases, microbiologic culture and PCR for Mycobacterium tuberculosis in 45.8%. For the 1999-2008 series, histological examination yielded a diagnosis in 69% of cases, culture in 38.5%. Spinal lesions in 4 patients with previous histories of malignancy were assumed to be metastatic and treated with radiation at outside institutions. After biopsy, all were revealed to be spondylodiscitis. CONCLUSIONS: Percutaneous CT-guided needle biopsy is the mainstay of diagnosis for spine lesions of unknown etiology, thus guiding appropriate treatment. Histological diagnosis, when possible, is critical before initiation of therapy and may be helpful in cases where cultures are negative. In the case of a spinal lesion of unknown origin, even in the setting of a previous malignancy, metastasis should not be assumed; infection and new primary lesions should always be considered as part of the differential diagnosis.

Usefulness of 124I PET/CT imaging to predict absorbed doses in patients affected by metastatic thyroid cancer and treated with 131I.

AIM: The aim of this work was the evaluation of the usefulness of 124I PET/CT sequential scans to predict absorbed doses to metastatic thyroid cancer in patients undergoing 131I therapy. METHODS: From July 2011 until April 2012 8 patients affected by metastatic thyroid cancer were enrolled. Each patient underwent 4 PET/CT scans at 4, 24, 48, 72 h after the administration of about 74 MBq of 124I. Blood samples and whole body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT images were used to evaluate tumour doses with MIRD formalism and spheres model. The average administered 131I therapeutic activity was 6475 MBq (range: 3700-9250 MBq). RESULTS: 124I PET/CT images showed, with a very good resolution, all 131I avid lesions detected by post therapy whole body scans. The average dose rates for blood, red marrow and lesions were respectively: 6.58E-02 ± 1.64E-02 mGy/MBq, 5.73E-02 ± 1.57E-02 mGy/MBq, 2.22E+01 ± 1.62E+01 mGy/MBq. Three out of eight patients did not show any uptake of 124I in all PET/CT scans, despite high level of TSH and CT detectable lesions. Post-therapy 131I whole body scan confirmed the absence of focal iodine uptake. CONCLUSION: Negative 124I PET/CT images probably could be used as predictive of real absence of iodine avidity, avoiding all toxicity from useless 131I therapy. A higher number of patients is necessary to validate these preliminary results and a project is ongoing to compare MIRD results to voxel dosimetry based on Monte Carlo simulation.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

18[F]FDG small animal PET study of sorafenib efficacy in lymphoma preclinical models.

AIM: Kinase inhibitors have been proposed as novel therapeutic agents in different forms of solid tumours. The Food and Drug Administration (FDA) approved the use of Sorafenib, an oral multikinase inhibitor, for advanced renal carcinoma and unresectable hepatocellular carcinoma. On-going studies are investigating the efficacy of Sorafenib in other solid tumours such as melanoma and non-small cells lung carcinoma and pre-clinical models showed the efficacy of treatment with Sorafenib in murine models of renal cells carcinoma, breast cancer, colon carcinoma and melanoma. To our knowledge, Sorafenib has never been employed in human lymphoma. The aim of the present study was to assess the efficacy of Sorafenib in murine models of human anaplastic large cells lymphoma (ALCL) and Hodgkin lymphoma (HD). METHODS: Sorafenib cytotoxicity was assessed in vitro and growth inhibition (IC50) was calculated. Cells were assayed for Caspase-3 to measure apoptosis. Human ALCL and HD xenografts in NOD/SCID mice were monitored by small animal positron emission tomography (PET) and computed tomography (CT) over time. Tumour bearing animals were randomly selected to receive treatment with Sorafenib or no treatment. Pathology was available in all cases. RESULTS: Sorafenib efficacy on cells proliferation and apoptosis (IC50: HD=0.0343 mg/L; ALCL=0.319 mg/L) was confirmed in vitro. Caspase-3 production showed a dose-dependent trend reaching significantly higher values for 0.046 mg/L and 0.465 mg/L drug concentrations in both cell lines. In vivo experiments showed a progressive increase of tumour lesions metabolism and dimensions regardless treatment. CONCLUSION: Sorafenib showed a good cytotoxic effect in vitro especially on human HD cell line, but these findings were not confirmed in vivo. The strong discrepancy between in vitro and in vivo results suggests that further studies are needed to better acknowledge the biodistribution and metabolism of Sorafenib in NOD/SCID mice. Factors influencing drug availability at tumour site or differences in the downstream pathways may be responsible for the scarse effect of treatment.

Non FDG PET.

2- [(18)F]-fluoro-2-deoxy-D-glucose (FDG) is the radiopharmaceutical most frequently used for clinical positron emission tomography (PET). However, FDG cannot be used for many oncological, cardiological, or neurological conditions, either because the abnormal tissue does not concentrate it, or because the tissues under investigation demonstrate high physiological glucose uptake. Consequently, alternative PET tracers have been produced and introduced into clinical practice. The most important compounds in routine practice are (11)C-choline and (18)F-choline, mainly for the evaluation of prostate cancer; (1)C-methionine for brain tumours; (118)F-DOPA ((18)F-deoxiphenilalanine) for neuroendocrine tumours and movement disorders; (68)Ga-DOTANOC (tetraazacyclododecanetetraacetic acid-[1-Nal3]-octreotide) and other somatostatin analogues for neuroendocrine tumours; 11C-acetate for prostate cancer and hepatic masses and 18F-FLT (3-deoxy-3-fluorothymidine) for a number of malignant tumours. Another impetus for the development of new tracers is to enable the investigation of biological processes in tumours other than glucose metabolism. This is especially important in the field of response assessment, where there are new agents that are targeted more specifically at angiogenesis, hypoxia, apoptosis and other processes.