Phase III Study of 18F-PSMA-1007 Versus 18F-Fluorocholine PET/CT for Localization of Prostate Cancer Biochemical Recurrence: A Prospective, Randomized, Crossover Multicenter Study.

The objective of this study was to compare 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT for the localization of prostate cancer (PCa) biochemical recurrence. Methods: This prospective, open-label, randomized, crossover multicenter study included PCa patients with prior definitive therapy and suspected PCa recurrence. All men underwent both 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT (102 received 18F-PSMA-1007 PET/CT first and 88 received 18F-fluorocholine PET/CT first). All images were assessed independently by 3 readers masked to all clinical information using a 3-point qualitative scale (0 = no recurrence, 1 = undetermined, and 2 = recurrence). Patients were monitored for approximately 6 mo. An independent panel with a urologist, radiologist, and nuclear physician reviewed all clinical data, including imaging and response to therapy, but were masked regarding PET/CT information; acting in consensus, they determined a patient-based and region-based composite standard of truth for PCa lesions. The "correct detection rates" for PCa lesions on a patient basis for each radiopharmaceutical were compared for the 3 readers individually and for the "average reader." Secondary objectives included determining whether PET/CT findings affected diagnostic thinking (impact of a test result on posttest vs. pretest probability of a correct diagnosis), therapeutic decision making (description and quantification of impact of diagnostic information gained with both radiopharmaceuticals on patient management), and adequacy of management changes. Results: A total of 190 patients were included. The primary endpoint was met. The overall correct detection rates were 0.82 for 18F-PSMA-1007 and 0.65 for 18F-fluorocholine (P < 0.0001) when undetermined findings were considered positive for malignancy and 0.77 and 0.57, respectively (P < 0.0001), when undetermined findings were considered negative for malignancy. A change in diagnostic thinking due to PET/CT was reported in 149 patients; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 93 of these patients. In 122 patients, PET/CT led to an adequate diagnosis that benefited the patient; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 88 of these patients. Conclusion: 18F-PSMA-1007 PET/CT is superior to 18F-fluorocholine PET/CT for the localization of PCa recurrence. Decision making was more beneficial when based on 18F-PSMA-1007 PET/CT results.

EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA).

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.

Survey by the French Medicine Agency (ANSM) of the imaging protocol, detection rate, and safety of 68Ga-PSMA-11 PET/CT in the biochemical recurrence of prostate cancer in case of negative or equivocal 18F-fluorocholine PET/CT: 1084 examinations.

INTRODUCTION: Despite growing evidence of a superior diagnostic performance of 68Ga-PSMA-11 over 18F-fluorocholine (FCH) PET/CT, the number of PET/CT centres able to label on site with gallium-68 is still currently limited. Therefore, patients with biochemical recurrence (BCR) of prostate cancer frequently undergo FCH as the 1st-line PET/CT. Actually, the positivity rate (PR) of a second-line PSMA-11 PET/CT in case of negative FCH PET/CT has only been reported in few short series, in a total of 185 patients. Our aims were to check (1) whether the excellent PR reported with PSMA-11 is also obtained in BCR patients whose recent FCH PET/CT was negative or equivocal; (2) in which biochemical and clinical context a high PSMA-11 PET/CT PR may be expected in those patients, in particular revealing an oligometastatic pattern; (3) whether among the various imaging protocols for PSMA-11 PET/CT used in France, one yields a significantly highest PR; (4) the tolerance of PSMA-11. PATIENTS AND METHODS: Six centres performed 68Ga-PSMA-11 PET/CTs during the first 3 years of its use in France. Prior to each PET/CT, the patient's data were submitted prospectively for authorisation to ANSM, the French Medicine Agency. The on-site readings of 1084 PSMA-11 PET/CTs in BCR patients whose recent FCH PET/CTs resulted negative or equivocal were pooled and analysed. RESULTS: (1) The overall PR was 68%; for a median serum PSA level (sPSA) of 1.7 ng/mL, an oligometastatic pattern (1-3 foci) was observed in 31% of the cases overall; (2) PR was significantly related to sPSA (from 41% if < 0.2 ng/mL to 81% if ≥ 2 ng/mL), to patients' age, to initial therapy (64% if prostatectomy vs. 85% without prostatectomy due to frequent foci in the prostate fossa), to whether FCH PET/CT was negative or equivocal (PR = 62% vs. 82%), and to previous BCR (PR = 63% for 1st BCR vs. 72% in case of previous BCR); (3) no significant difference in PR was found according to the imaging protocol: injected activity, administration of a contrast agent and/or of furosemide, dose length product, one single or multiple time points of image acquisition; (4) no adverse event was reported after PSMA-11 injection, even associated with a contrast agent and/or furosemide. CONCLUSION: Compared with the performance of PSMA-11 PET/CT in BCR reported independently of FCH PET/CT in 6 large published series (n > 200), the selection based on FCH PET/CT resulted in no difference of PSMA-11 PR for sPSA < 1 ng/mL but in a slightly lower PR for sPSA ≥ 1 ng/mL, probably because FCH performs rather well at this sPSA and very occult BCR was over-represented in our cohort. An oligometastatic pattern paving the way to targeted therapy was observed in one fourth to one third of the cases, according to the clinico-biochemical context of the BCR. Systematic dual or triple acquisition time points or administration of a contrast agent and/or furosemide did not bring a significant added value for PSMA-11 PET/CT positivity and should be decided on individual bases.

Lymphoscintigraphy for Sentinel Node Mapping in Head and Neck Cancer.

The aim of this comprehensive review is to describe and analyze the role of the sentinel node mapping in head and neck cancers. For this purpose, head and neck neoplasms have been categorized in cutaneous malignancies and neoplasms of the upper aerodigestive tract. A concise description of lymphatic drainage will be the "prelude" for each section, as well as the description of the injection techniques, when specific. Concisely, the attention has been focused on detection rate of the sentinel node by lymphoscintigraphy for each cancer, and for those patients in which the sentinel lymph node has been identified, true-positives rates, false-negative rates, and overall accuracy has been pointed out. Overall, in cutaneous neoplasms of the head and neck, the detection rate is higher than 90%, however the false-negative rate is still an issue, in particular in melanoma, inducing the need for newer developments. In fact, new tracers and techniques are already available, while prospective multicenter trials exploring the outcome impact are needed in the near future. For the upper aerodigestive tract and in particular oral cavity and oropharynx, sentinel lymph node identification by lymphoscintigraphy allows avoiding unnecessary neck dissection and/or node irradiation. Even in this case, the main limit remains the risk of false-negative rates. While, for patients affected by laryngeal and hypopharyngeal cancers the data seem very limited and, although the feasibility has been demonstrated, performances of this lymphoscintigraphy still need to be confirmed by multicenter studies.

Selective internal radiation therapy of hepatic tumors: Morphologic and functional imaging for voxel-based computer-aided dosimetry.

INTRODUCTION: Selective Internal Radiation Therapy (SIRT) is used for the treatment of hepatic tumors. The aim of this retrospective study was to compare two dosimetric approaches based on 99mTc-MAA SPECT/CT and 90Y PET/CT, using Simplicit90Y™ versus the supplier suggested method of activity calculation. MATERIAL AND METHODS: A total of 19 patients underwent 21 SIRT after baseline angiography and 99mTc-MAA SPECT/CT, followed by 90Y PET/CT. Overlap between 99mTc-MAA and 90Y-microspheres was quantified with different thresholds isocontours. The perfused volume and tumor absorbed dose were estimated using Simplicit90Y™ based on SPECT/CT and PET/CT, then compared with the supplier suggested method. These data were related to overall survival to evaluate their prognostic impact. RESULTS: The overlap between PET/CT and SPECT/CT was dependent on thresholds, decreasing with an increasing threshold. The overlap between the 99mTc-MAA and 90Y-microspheres biodistributions versus the tumor distribution on morphological imaging was suboptimal, in particular for small tumor volume. The tumor absorbed dose estimated after 90Y PET/CT was not different from tumor absorbed dose estimated after SPECT/CT. The Perfused lobe absorbed dose was significantly lower while the volume of the perfused lobe was significantly higher when estimated by Simplicit90Y™ compared to the supplier suggested conventional approach. A statistical parameter based on overlap between tumor and 90Y-microspheres distribution as well as tumoral dosimetry was significantly related to the overall survival. CONCLUSION: Post-treatment imaging remains paramount to estimate the irradiation dosimetry, due to an imperfect overlap. The perfused volume could be estimated from functional imaging, given its impact on dosimetry. Finally, survival seems related to tumoral overlap and dosimetry.

Sentinel Node Mapping in Gynecologic Cancers: A Comprehensive Review.

Gynecologic cancers are one of the most important causes of women death worldwide. The sentinel lymph node concept was introduced by Cabanas in 1977 for the penile cancer. This technique was proven safe and feasible in selected cancers such as breast cancer, melanoma, or some gynecologic cancers. Sentinel lymph node mapping is increasingly used in early stages of cervical or vulvar cancer in particular due to the safety, high detection rate, and sensitivity of the technique. In this review, we will discuss in depth the most recent evidence of nuclear medicine and other techniques used to determine the status of the sentinel lymph node in women affected by gynecologic neoplasms. Although significant efforts have been already done in order to address several issues, there are still determined questions without a clear answer, in particular for endometrial, ovarian, and vaginal neoplasms.

Isolated Muscular Sarcoidosis Revealed by Hypercalcemia and 18F-FDG PET/CT.

A 43-year-old woman, with previous history of renal lithiasis, was admitted on an emergency for severe hypercalcemia fortuitously discovered in a context of rapidly progressive kidney failure. An F-FDG PET/CT performed to rule out underlying malignancy revealed an intense diffuse and isolated muscular FDG uptake with fascia infiltration on the CT finding. A muscular biopsy was performed and demonstrated a non-necrosing granuloma with multinucleated giant cells consistent with muscular sarcoidosis. A corticotherapy was started with a rapid normalization of serum calcium level. The follow-up F-FDG PET/CT 4 months later showed a complete response of the sarcoidosis myositis.

FDG PET/CT of Gardnerella vaginalis Infection.

We report the case of a 23-year-old woman with a history of cystic fibrosis and bilung transplantation, who presented clinically cervical swollen lymph nodes with alteration of her general state. F-FDG PET/CT was performed because of lymphoma suspicion and showed cervical and pelvic hypermetabolic lymphadenopathies, with linear vaginal hypermetabolism. There was an increase of lactate dehydrogenase, and Epstein-Barr virus detection was negative. A right cervical lymph node biopsy was performed, with no lymphoma involvement. Complementary microbiological investigations showed positive results for Gardnerella vaginalis. F-FDG PET/CT lymphatic node hypermetabolism is not specific to lymphoma, particularly in immunocompromised patients.

18F-fluorodeoxyglucose positron emission tomography is useful for the diagnosis of intraocular sarcoidosis in patients with a normal CT scan.

AIM: To assess the usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and the predictive factors for the diagnosis of sarcoidosis in patients with uveitis who have normal thoracic tomography. METHODS: We retrospectively reviewed 67 consecutive patients with uveitis of unknown aetiology or a suspected sarcoidosis. All patients with normal thoracic tomography underwent an 18F-FDG PET/CT, which was blindly reinterpreted. We then assessed the proportion of positive 18F-FDG PET/CT and the impact on the final aetiology, using Abad's criteria for the diagnosis of intraocular sarcoidosis. RESULTS: 19 of the 67 patients (28.4%) had mediastinal hypermetabolic foci on their 18F-FDG PET/CT consistent with sarcoidosis. It identified a biopsy site in two cases, which were consistent with sarcoidosis. At the end of the study, six patients (10%) had a proven sarcoidosis, six patients (9%) were considered as having a presumed sarcoidosis and 18 patients (26.9%) as having indeterminate sarcoidosis. 18F-FDG PET/CT enabled the diagnosis of presumed sarcoidosis in these six patients. An older age at diagnosis (p=0.004) and the presence of synechiae (p=0.02) were significantly related to an abnormal 18F-FDG PET/CT, with a trend for an elevated ACE (p=0.0993). We established a nomogram to estimate the probability of having positive findings on the 18F-FDG PET/CT according to different predictive factors. CONCLUSION: 18F-FDG PET/CT enabled the diagnosis of intraocular sarcoidosis even in patients with a normal CT scan. Older age at diagnosis, presence of synechiae and elevated ACE are associated with positive findings on 18F-FDG PET/CT consistent with sarcoidosis.

Feasibility and Evaluation of Automated Methods for Radiolabeling of Radiopharmaceutical Kits with Gallium-68.

OBJECTIVES: Recent gallium-68 labeled peptides are of increasing interest in PET imaging in nuclear medicine. Somakit TOC® is a radiopharmaceutical kit registered in the European Union for the preparation of [68Ga]Ga-DOTA-TOC used for the diagnosis of neuroendocrine tumors. Development of a labeling process using a synthesizer is particularly interesting for the quality and reproducibility of the final product although only manual processes are described in the Summary of Product (SmPC) of the registered product. The aim of the present study was therefore to evaluate the feasibility and value of using an automated synthesizer for the preparation of [68Ga]Ga-DOTA-TOC according to the SmPC of the Somakit TOC®. METHODS: Three methods of preparation were compared; each followed the SmPC of the Somakit TOC®. Over time, overheads, and overexposure were evaluated for each method. RESULTS: Mean±SD preparation time was 26.2±0.3 minutes for the manual method, 28±0.5 minutes for the semi-automated, and 40.3±0.2 minutes for the automated method. Overcost of the semi-automated method is 0.25€ per preparation for consumables and from 0.58€ to 0.92€ for personnel costs according to the operator (respectively, technician or pharmacist). For the automated method, overcost is 70€ for consumables and from 4.06€ to 6.44€ for personnel. For the manual method, extremity exposure was 0.425mSv for the right finger, and 0.350mSv for the left finger; for both the semi-automated and automated method extremity exposure were below the limit of quantification. CONCLUSION: The present study reports for the first time both the feasibility of using a [68Ga]- radiopharmaceutical kit with a synthesizer and the limits for the development of a fully automated process.

Usual and unusual pitfalls of 18F-FDG-PET/CT in lymphoma after treatment: a pictorial review.

Fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is now a standard of care in initial staging and treatment evaluation of lymphomas. It is also used in the interim evaluation in diffuse large B cell lymphoma and Hodgkin lymphoma. However, several pitfalls may occur during or after treatment, because of the nonspecificity of F-FDG for lymphoma disease and treatment as immunotherapy, thus possibly induces misinterpretation and wrong treatment decision. The aim of this pictorial review is to provide an illustrated tutorial of the most frequent pitfalls found on F-FDG-PET/CT during or after treatment.

The role of 18F-FDG-PET/ceCT in peritoneal mesothelioma.

PURPOSE: The aim of this study was to assess glucose metabolism of multicystic peritoneal mesothelioma and epithelioid peritoneal mesothelioma by fluorine-18 fluorodeoxyglucose (F-FDG)-PET/contrast-enhanced computed tomography (ceCT) and to assess its prognostic impact. MATERIALS AND METHODS: Twenty-three (14 women) patients, without previous treatment, underwent F-FDG-PET/ceCT before peritoneal mesothelioma cytoreductive surgery and intraperitoneal chemotherapy. F-FDG-PET/ceCT was interpreted prospectively as positive or negative. Maximum standardized uptake value (SUVmax) of each lesion was measured retrospectively on the basis of postsurgery data. At laparotomy, disease extension was estimated with the Peritoneal Cancer Index. The median follow-up was 27 months (95% confidence interval: 12.9-37.8); progression-free survival (PFS) was recorded. RESULTS: Nine patients were affected by multicystic and 14 were affected by epithelioid peritoneal mesothelioma. PET showed mild focal uptake in one case of multicystic peritoneal mesothelioma, whereas in eight patients, no abnormal uptake was observed. PET was positive in 12/14 patients with epithelioid peritoneal mesothelioma. Sensitivity, specificity and accuracy were respectively 86, 89 and 87%; the qualitative assessment was statistically different (P=0.0020, χ). Multicystic peritoneal mesothelioma histology was significantly associated with lower SUVmaxlesion (P=0.0061), SUVmaxlesion/liver (P=0.0025), Peritoneal Cancer Index, younger age, and it was observed only in women.Recurrence was observed on nine patients affected by epithelioid peritoneal mesothelioma, whereas no recurrences were observed among multicystic peritoneal mesothelioma patients. SUVmaxlesion (P=0.0278) and age (P=0.0241) were significantly associated with PFS in patients with epithelioid peritoneal mesothelioma. CONCLUSION: F-FDG-PET/ceCT showed significant differences between multicystic and epithelioid peritoneal mesothelioma, whereas SUVmaxlesion was associated with PFS in the latter. Although multicentre prospective studies are necessary, F-FDG-PET/ceCT appears to be a promising tool in patients affected by peritoneal mesothelioma.

Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

OBJECTIVE: The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. RESULTS: Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p < 0.001). ROC curve showed significantly large AUC for both the parameters (p < 0.05). Parotid UP and submandibular EF, assessed by univariated and multivariate logistic regression, showed a significant and independent correlation with pSS diagnosis (p value <0.05). No correlation was found between SGdS semi-quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. CONCLUSION: SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. CLINICAL RELEVANCE: SGdS should be the first-line imaging technique in patients with suspected pSS.

Diffuse Subcutaneous Fat Involvement in a Marginal Zone Lymphoma.

Marginal zone lymphoma (MZL) is usually considered not avid for FDG. We report a case of a 57-year-old man with an MZL suspected for transformation. FDG-PET/CT showed a diffuse atypical involvement of subcutaneous fat, without sign suggestive for a transformation. No cutaneous involvement was clinically evident. A random subcutaneous biopsy was performed and showed the presence of MZL.

18F-FDG-PET/CT of peritoneal tumors: a pictorial essay.

Cancer imaging on the peritoneum is quite difficult on PET/CT because of the particular anatomical features of this membrane. The abdominal cavity can be the seat of very different primary or secondary tumoral lesions, with heterogeneous aggressiveness and variable fluorine-18 fluorodeoxyglucose uptake and patterns. We aimed to depict a spectrum of appearances with abnormal fluorine-18 fluorodeoxyglucose uptakes localized on the peritoneum in frequent conditions such as peritoneal carcinomatosis and in rarer disease such as desmoplastic round cell tumor.

Diffusion-weighted MRI and 18F-FDG-PET/CT imaging: competition or synergy as diagnostic methods to manage sarcoma of the uterus? A systematic review of the literature.

AIM: To evaluate the diagnostic performance of fluorine-18-fluorodeoxyglucose PET/computed tomography (F-FDG-PET/CT) and MRI with diffusion-weighted images (DWI) in uterine sarcomas (US). PATIENTS AND METHODS: A systematic review was performed on Medline, ISI web of knowledge, and Scopus databases for studies reporting the diagnostic performance of F-FDG-PET/CT and DWI-MRI in US published up to 15 February 2016. Exclusion criteria were articles with fewer than five cases of US, without DWI-MRI, and previous series of patients from the same researcher team. RESULTS: Seven studies were selected for DWI-MRI and 11 for F-FDG-PET/CT. DWI-MRI was used only to characterize uterine tumors, and showed a good sensitivity but a low specificity. The apparent diffusion coefficient value seems to be the most discriminant between benign and malignant lesion. No data were available on staging and restaging.F-FDG-PET/CT improved patients' management when used for characterization, staging, and restaging because of its quite good accuracy. To date, few data exist on the prognostic role of F-FDG-PET/CT. Well-designed multicenter prospective trials are needed to establish definitively the exact role of imaging in the management of US. CONCLUSION: Both DWI-MRI and F-FDG-PET/CT have their own advantages, and should be performed in a 'one stop shop' scan in the near future by PET/MRI engines.

Cat-Scratch Disease: A Pitfall for Lymphoma Evaluation by FDG-PET/CT.

FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.

Role of fluorine-18 fluorodeoxyglucose PET/CT in head and neck oncology: the point of view of the radiation oncologist.

Squamous cell carcinoma is the most common malignant tumour of the head and neck. The initial TNM staging, the evaluation of the tumour response during treatment, and the long-term surveillance are crucial moments in the approach to head and neck squamous cell carcinoma (HNSCC). Thus, at each of these moments, the choice of the best diagnostic tool providing the more precise and larger information is crucial. Positron emission tomography with fluorine-18 fludeoxyglucose integrated with CT (18F-FDG-PET/CT) rapidly gained clinical acceptance, and it has become an important imaging tool in routine clinical oncology. However, controversial data are currently available, for example, on the role of 18F-FDG-PET/CT imaging during radiotherapy planning, the prognostic value or its real clinical impact on treatment decisions. In this article, the role of 18F-FDG-PET/CT imaging in HNSCC during pre-treatment staging, radiotherapy planning, treatment response assessment, prognosis and follow-up is reviewed focusing on current evidence and controversial issues. A proposal on how to integrate 18F-FDG-PET/CT in daily clinical practice is also described.