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.

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.

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.

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.

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.

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.

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.

[The document of chemical risk assessment: experiences in small companies]. / Il documento di valutazione del rischio chimico: esperienze nelle piccole imprese.

Were examined 60 documents of chemical risk assessment of companies from 19 municipalities in the provinces of Siena and Grosseto. The review of evaluations was conducted initially by checking the internal coherence of the documents. What emerged was subsequently analyzed together with the staff who performed the inspection. Although in 12 companies has been declared the presence of carcinogens, in only 5 the evaluation of exposure have been done using measures, others have used models or other techniques. Overall assessment showed that only 8 out of 60 (13.3%) were wrote correctly.

Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer.

The epidermal growth factor receptor (EGFr) is one of the most studied molecules as a target for cancer therapy. Over these last few years, several studies attempting to identify predictive biomarkers of treatment response, such as the receptor status or other molecules related to the downstream signalling pathway, have been conducted. However, from a clinical point of view, the information obtained from ex vivo analyses still has various limitations that may be overcome by the combination with molecular imaging technologies which may provide a noninvasive, global, in vivo evaluation of the molecular tumour background. The aim of this review is to report the preclinical results of all positron emission tomography (PET) tracers synthesized until now for in vivo detection of EGFr in cancer. Two classes of PET compounds have been developed: labelled small molecules such as tyrosine kinase inhibitors and labelled monoclonal antibodies. The in vitro and in vivo results of these PET tracers are very different depending on the chemical properties, positron emission radionuclide, or animal models. As a consequence, various critical questions are still open, and the implications of a translation in the clinical setting for EGFr imaging in cancer patients is discussed.

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.

Conventional and novel PET tracers for imaging in oncology in the era of molecular therapy.

In the last ten years, the development of several novel targeted drugs and the refinement of state of the art technologies such as the genomics and proteomics and their introduction to clinical practice have revolutionized the management of patients affected by cancer. However, everyday practice points out several clinical questions: the difficulty of response assessment to new drugs especially using standard RECIST criteria that do not provide information on biological, vascular or metabolic variations; the inadequate selection of patients who are likely to benefit from a targeted therapy excluding those with breast cancer and gastrointestinal stromal tumours; the need to know the global biological background of diseases especially in metastatic setting using repeatable non-invasive procedures. Molecular imaging could provide information on in vivo distribution of biological markers in response to targeted therapy and could improve the selection of patients before therapies. The aim of this review is to analyze the current role of conventional and innovative positron emission tomography (PET) radiotracers in clinical practice and to explore the promising perspectives of molecular imaging in cancer research.

Molecular imaging and targeted therapies in oncology: new concepts in treatment response assessment. a collection of cases.

The widespread use of several new non-cytotoxic drugs and the significant improvements in functional imaging highlights a number of difficulties in monitoring, interpreting and predicting treatment response in clinical practice. Certain guidelines for disease assessment after therapy are already available: the traditional Response Evaluation Criteria in Solid Tumours guidelines based on tumour size variations using conventional imaging technologies, the recent combined method developed by Choi and colleagues in gastrointestinal stromal tumour treated with tyrosine kinase inhibitors based on tumour density variations using computed tomography (CT), and the European Organization for Research and Treatment of Cancer criteria based on tumour glucose metabolism variations using fluorodeoxyglucose (FDG) positron emission tomography (PET). At the moment combined PET/CT response criteria are still not available. A number of new PET compounds other than FDG are also currently being developed to visualize specific cellular and molecular tumour pathways but their role in assessment and prediction of cancer treatment response has not yet been thoroughly investigated in a large series. However, in clinical practice many oncologists treat cancer patients with targeted therapies or chemotherapy and evaluate the response using conventional or functional imaging without appropriate and standardized guidelines. The aim of this study was to present a selection of clinical cases that illustrate the usefulness of new PET tracers and efficacy evaluation of new drugs. In the era of molecular imaging and molecular therapies, these cases highlight the urgency to develop new criteria for treatment assessment and the exigency of correctly interpreting the biological information obtained from new technologies, and introduce new concepts that require further investigation in clinical trials.

68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors.

OBJECTIVES: The aim of this work was the evaluation of biodistribution and radiation dosimetry of (68)Ga-DOTANOC in patients affected by neuroendocrine tumors. MATERIALS AND METHODS: We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of (68)Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40-50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software. RESULTS: A physiological uptake of (68)Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys (9.0E-02+/-3.2E-02mSv/MBq). The mean effective dose equivalent (EDE) was 2.5E-02+/-4.6E-03 mSv/MBq. DISCUSSION AND CONCLUSIONS: The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and (68)Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that (68)Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds.

18F-FDG small animal PET for early detection of human anaplastic large cells lymphoma xenograft in immunocompromised mice.

The purpose of the present study was to assess if small animal PET is useful for serially monitoring the development of a human anaplastic large cell lymphoma (ALCL) murine xenograft and for the early selection of tumour bearing animals. The human ALCL Karpas 299 cell line was subcutaneously injected in 6-week-old NOD/SCID (non-obese diabetic/NCrCrl- Prkdc) mice (10(7) cells/mouce in 150 pil FBS) at the right flank level. Small animal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was serially performed (intravenous injected dose: 20 MBq in < 0.15 ml, uptake time: 60 min, image acquisition: 1 bed position of 15 min): early PET at 2 days after cell inoculation in 4/8 mice and at 4 days in the remainig 4/8, later PET scans were performed in all the animals at 7, 14, 21 and 28 days after inoculation. The images were evaluated visually and the tumour to background ratio (TBR) was used for semiquantitative analysis. Pathology sections were obtained in all cases. PET detected the presence of the tumour as early as seven days after inoculation in 4/8 mice and at 14 days in 2/8. Of the two remaining mice, one died after the first PET scan (thus preventing any evaluation of detection time) while the other showed a microscopic neoplastic infiltration at tracheal level at autopsy. Mean TBR progressively increased in all positive cases, particularly in the first 3 weeks, reaching a plateau afterwards. PET was positive in 6/8 (75%) animals, detecting the presence of viable tumour cells earlier than macroscopic evaluation, thus may be used for the early identification of tumour bearing animals.

Clinical applications of 68Ga-DOTANOC in neuroendocrine tumours.

Neuroendocrine tumours (NET) are relatively rare neoplasms affecting principally the gastroenteropancreatic tract, but with potential ubiquitary location, as the neural crest cells, origin of this group of tumours, are dispersed in various organs and tissues. After the discovery of somatostatin receptors (SSTR) over-expression in this group of neoplasms, NET management has significantly improved. This is witnessed by the development of new tracers in positron emission tomography (PET) imaging of NETs belonging to the family of radio-labelled somatostatin analogues, that significantly improved the accuracy of diagnosis and, more recently, opened the way to the innovative targeted radionuclide therapies. First introduced in clinical application in 2005, 68Ga-DOTANOC (one of the most used radio-labelled somatostatin analog for PET imaging) has revealed promising results in preliminary studies for the main clinical indications: staging NET; suspected NET of unknown primary; follow-up, restaging and, finally, for pre- and post-treatment evaluation of receptor radionuclide therapies. Due to its technically simple production, favourable biodistribution, biokinetics, dosimetry and high affinity for SSTR and thanks to the possibility of hybrid scans PET/computed tomography (CT) with better spatial resolution and localisation of the lesions, 68Ga-DOTANOC can advance as the new gold standard for imaging in neuroendocrine tumours.

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.

Gallium-68 PET: a new frontier in receptor cancer imaging.

Neuroendocrine tumours (NET) are rare tumours that occur most commonly in the GI tract. Various labelled somatostatin analogues are used to image NET expressing somatostatin receptors (SSTR). In traditional nuclear medicine, most peptides used in imaging NET have been labelled with indium-111, the commonest being indium-111-octreotide (111In-octreotide). Unfortunately, the unfavourable physical qualities of In-111 make it unsuitable for detecting small tumour deposits. The recent introduction of gallium-68-1,4, 7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (gallium-68-DOTA) compounds for positron emission tomography (PET) imaging has significantly improved the quality of imaging NET through improved resolution of PET and higher affinity of the new generation of peptides to SSTR. In the present paper, we discuss the clinical and research applications of PET radio-tracers for evaluating NET, in particular gallium-68-DOTA compounds. The recent introduction of PET imaging with gallium-68 has major bearings in current and future clinical practice. Its labelling with DOTA compounds has cleared the way for somatostatin receptor imaging with a viable PET agent, with all its inherent imaging advantages compared to single photon imaging. The pre-clinical and clinical applications of this technique has been successful in a variety of tumours, particularly NET and its labelling with other ligands and molecules will improve the management of other tumours and the assessment of infection.

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.