Assessment of the Incremental Diagnostic Value of Florbetapir F 18 Imaging in Patients With Cognitive Impairment: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study.

IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.

18F-Fluorocholine PET/CT Finding of a Vertebral Hemangioma.

The uptake of F-fluorocholine (FCH), a radiopharmaceutical used to study patients with prostate cancer, follow both the phosphorylcholine and acetylcholine synthesis. FCH uptake is not specific of neoplastic cells because phospholipids are a structural constituent of the membrane of all cells. Thus, PET/CT with FCH show several areas of physiologic uptake. The skeleton concentrates only mild amounts of FCH, thus a diffuse faint uptake of the radiopharmaceutical is present at a PET/CT study. Herein we present the case of a patient in which PET/CT evidenced a sharply defined vertebral "cold" area of reduced FCH uptake corresponding to a vertebral hemangioma.

Positron Emission Tomography for the Response Evaluation following Treatment with Chemotherapy in Patients Affected by Colorectal Liver Metastases: A Selected Review.

The aim of the present paper is to review the scientific literature concerning the usefulness of (18)F-FDG PET/CT in the evaluation of response to chemotherapy in patients affected by liver metastases from colorectal cancer. Material and Methods. Studies were identified by searching PubMed electronic databases. Both prospective and retrospective studies were included. Information regarding the figure of merit of PET for the evaluation of therapy response was extracted and analyzed. Results. Existing data suggests that (18)F-FDG PET/CT may have an outstanding role in evaluating the response. The sensitivity of PET in detecting therapy response seems to be greater than conventional imaging (CT and MRI). PET/CT response is strictly related to better overall survival and progression-free survival. Conclusions. PET/CT is more than a promising technique to assess the response to chemotherapy in colorectal and liver metastases. However, to be fully validated, this examination needs further studies by recruiting more patients.

ImmunoPET in Neoplasms of Gastrointestinal Tract, Liver and Pancreas in the XXIst Century: Bridging the Gap Between Diagnosis and Therapy.

Monoclonal antibodies (mAbs) are produced by clones of a unique parent cell which has monovalent affinity and can bind to the same epitope. The chronological breakthrough in mAbs clinical utilization was in 1975, when it becomes possible to produce mAbs to known antigens and immortalize the cell lines. However, the clinical usefulness of mAbs was hampered for many years, basically because of their immunogenicity due to the murine origin. This situation lasted until 1988 when a technique to humanize mAbs was defined. Nuclear Medicine researchers were very quick to gathered the opportunity provided by the development of mAbs. The first papers reporting the preclinical use of radiolabelled mAbs date the early 80's soon followed by the first pivotal use in humans. However, mAbs did not gain a wide clinical use for several reasons connected to the chemistry and biochemistry of radiolabelled mAbs the emergence of clinical 18F-FDG PET. However, the "magic bullet" concept has resisted in the cultural background of Nuclear Medicine physicians for almost twenty years, and has regained importance with the development of engineered mAbs. Herein we present a selected review of preclinical and clinical studies of PET/CT with mAbs in gastrointestinal malignancies.

Unusual widespread metastatic subcutaneous lesions in a patient with ileal carcinoid evidenced by 68Ga-DOTATOC PET/CT.

68Ga-DOTATOC PET/CT has been widely validated in diagnosis and follow-up of carcinoid. A 47-year-old woman with ileal carcinoid underwent a 68Ga-DOTATOC PET/CT for restaging purposes. Images showed extensive liver involvement and also a widespread metastatic subcutaneous metastases in the right chest wall and in the right laterocervical region. The presence of multiple soft-tissue metastases, as described in our case and imaged with 68Ga-DOTATOC, represents a very rare clinical entity.

Extraosseous myocardial uptake incidentally detected during bone scan: report of three cases and a systematic literature review of extraosseous uptake.

Bone scintigraphy is widely considered as an important technique able to investigate various pathological conditions of the skeletal system. Many unexpected extraosseous uptakes have been reported in literature. We present here three cases of unexpected 99mTc-oxidronate (HDP) myocardial extraosseous uptakes in patients undergoing bone scan for staging purposes. In particular, we present the first reported case ofa myocardial uptake in a patient with IgM-related amyloidosis. Subsequently, we perform a review of the existing literature about extraosseous uptakes.

Unsuspected Active Sarcoidosis Diagnosed by 18F-FDG PET/CT During the Search for a Primary Tumour in a Patient with Bone Lesions.

Sarcoidosis is a systemic chronic inflammatory disease of unknown aetiology, characterised by granulomatous lesions with heterogeneous clinical manifestations affecting multiple organs and tissues. Although the respiratory system is most commonly affected, the disease may also present with bone lesions. We report the case of a 31-year-old woman who presented with low back pain and no history of cancer and who was found to have suspicious lesions involving the entire spine on magnetic resonance imaging (MRI). The patient underwent 18F-fluorodeoxyglucose (FDG) PET/CT to search for a primary tumour and for staging purposes. 18F-FDG PET/CT revealed a pattern of hypermetabolic activity in widespread skeletal lesions and in a single left cervical lymph node. The primary tumour was not found, thus suggesting a haematologic disorder. Subsequent biopsies of a cervical lymph node and of bone tissue from L4 revealed active sarcoidosis with no evidence of cancer. This underlines the importance of considering all alternatives when hypermetabolic lesions are found on 18F-FDG PET/CT. Furthermore, 18F-FDG PET can be very useful to indicate accessible sites for guiding fine-needle aspiration cytology (FNAC).

Role of ¹¹C-choline positron emission tomography/computed tomography in evaluating patients affected by prostate cancer with suspected relapse due to prostate-specific antigen elevation.

PURPOSE: The aim of this study was to evaluate the accuracy of (11)C-choline positron emission tomography/computed tomography (PET/CT) in restaging patients affected by prostate cancer and suspected relapse due to prostate-specific antigen (PSA) increase. We also aimed to determine a PSA cutoff that is most suited to the study in terms of best compromise between sensitivity and specificity. Secondary endpoints were a comparison between (11)C-choline PET/CT and histological results, clinical findings, and radiological imaging (CT and magnetic resonance imaging). MATERIALS AND METHODS: We retrospectively evaluated 210 patients (median ± SD age 70 ± 7 years) affected by prostate cancer who underwent (11)C-choline PET/CT. RESULTS: (11)C-choline PET/CT imaging was positive in 116 (55.2%) patients and negative in 94 (44.8%). Receiver operating characteristic (ROC) analysis showed that the highest accuracy (sensitivity 76.8%, specificity 92.5%) for the whole population was achieved when the PSA level of 1.26 ng/ml level was used as the cutoff value for interpreting the results (P = 0.0001 and the area under the ROC curve AUC 0.897). For patients treated with surgery or surgery plus radiotherapy the cutoff was 0.81 ng/ml (sensitivity 73.2%, specificity 86.1%). For patients treated with radiotherapy alone, the cutoff was 2.0 ng/ml (sensitivity 81.8%, specificity 92.9%). CONCLUSION: Our results indicate that (11)C-choline PET/CT is a useful diagnostic tool in patients affected by prostate cancer and a relapsed PSA level. The highest accuracy for all patients is obtained with a PSA cutoff level of 1.26 ng/ml, above which the imaging study is performed (0.81 ng/ml for patients treated with surgery or surgery plus radiotherapy and 2.0 ng/ml for patients treated with radiotherapy alone).

F18-FDG-PET/CT in a patient affected by Lynch syndrome.

Lynch syndrome (LS) is the most common hereditary syndrome that predisposes patients to colorectal cancer, and it accounts for 2-5% of the total burden of colorectal cancer. We report a case of a 61-year-old female affected by Lynch syndrome who underwent multiple adenocarcinoma resections, studied by F18-FDG-PET/CT for 5 years. This case report suggests a potential role of F18-FDG-PET/CT in the evaluation of patients affected by Lynch syndrome.

A patient with medullary thyroid carcinoma and right ventricular cardiac metastasis treated by (90)Y-Dotatoc.

Medullary thyroid carcinoma (MTC) is rare derived from C cells of the thyroid gland and represents approximately 5% of all thyroid carcinomas. We report a case of a 74 years old male with MTC, diagnosed in 2002 and treated with total thyroidectomy and lymphadenectomy. A metastatic lesion was diagnosed on the right ventricle by indium-111-octreoscan, fluorine-18-fluorodeoxyglucose-positron emission tomography/computerized tomography, echocardiography, magnetic resonance imaging, high resolution computed tomography and was confirmed by histopathology. We present the results of treatment of this patient with yttrium-90-DOTA-tyr(3)-octreotide.

Cetuximab in the treatment of metastatic mucoepidermoid carcinoma of the salivary glands: a case report and review of literature.

INTRODUCTION: Patients with metastatic mucoepidermoid carcinoma of salivary glands have a poor outcome. The epidermal growth factor receptor protein is overexpressed in approximately 70% of mucoepidermoid carcinoma patients and may represent a therapeutic target. However, whether treatment with anti-epidermal growth factor receptor agents is effective is unclear and clinical trials are difficult due to the rarity of the disease. Here we assessed the activity of cetuximab in mucoepidermoid carcinoma on a molecular basis. CASE PRESENTATION: We present the case of a 40-year old Caucasian man with a mucoepidermoid carcinoma of the major salivary glands who developed distant bone and visceral metastases despite platinum-based chemotherapy. Epidermal growth factor receptor was overexpressed and fluorescence in situ hybridization analysis demonstrated a chromosome 7 polysomy. The patient was treated with the monoclonal antibody cetuximab in combination with cisplatin. After 11 doses of cetuximab, the patient developed brain metastases but evidence of response was documented at all extracranial metastatic sites. CONCLUSION: This case report indicates that cetuximab can be active in mucoepidermoid carcinoma and may restore sensitivity to cisplatin in platinum-treated patients. Cetuximab does not cross the blood brain barrier and may select a metastatic clone to home the central nervous system while responding at other sites.

Possible additional value of 18FDG-PET in managing pancreas intraductal papillary mucinous neoplasms: preliminary results.

Although some clinical and radiological features may predict malignancy presence in intraductal papillary mucinous pancreas neoplasms, preoperative diagnosis remains difficult. In this study we present 7 patients with Intraductal Papillary Mucinous Neoplasm (IPMN) studied both with 18FDG-PET and magnetic resonance cholangiopancreatography (MRCP). A focal hypermetabolism was documented in 2 patients (the standardized uptake value in the neoplastic foci was 6.7 and 9), while absence of FDG uptake in the neoplasm area was recorded in the remaining 5 cases. Mean follow-up was 27 months (range 21-34). The final judgement was benign IPMN in 5 cases and malignant IPMN in 2. PET scan always correctly predicted the presence or absence of malignancy, while MRCP failed to detect malignancy in 3/7 cases. In conclusion, this preliminary experience suggests that 18FDG-PET may prove useful for malignancy detection in IPMN, improving differential diagnosis with benign intraductal papillary growth by functional data.

Value of gated SPECT in the analysis of regional wall motion of the interventricular septum after coronary artery bypass grafting.

PURPOSE: The aim of this study was the evaluation of septal wall motion, perfusion and wall thickening after CABG in two groups of consecutive patients, one with grafted left anterior coronary artery and no history of myocardial infarction, and the other with previous anteroseptal myocardial infarction and impaired septal motion before surgery. The issue addressed was the ability of gated SPECT to differentiate between true paradoxical septal motion, characterised by paradoxical wall motion, depressed ejection fraction (EF), poor viability and compromised wall thickening, and pseudo-paradoxical motion, characterised by abnormal wall motion and regional EF but preserved perfusion and wall thickening. METHODS: One hundred and thirty-two patients with previous anterior myocardial infarction, 82 patients with left anterior descending coronary disease and no history of myocardial infarction and 27 normal subjects underwent rest gated SPECT after 99mTc-sestamibi injection, according to the standard QGS protocol. Quantitative regional EF, regional perfusion, regional wall motion and regional wall thickening were determined using a 20-segment model. RESULTS: Despite the presence of similar regional wall motion impairment in patients with and patients without septal infarction, in terms of regional EF (2.5%+/-3% vs 1.9%+/-4.9% p=NS) and inward septal motion (3+/-4.9 mm vs 2.3+/-6.1 mm p=NS), significant differences were observed in both perfusion (74.7%+/-6.2% vs 63.3%+/-13%, p>0.0001) and regional wall thickening (17.2%+/-7.4% vs 12.6%+/-7.2%, p>0.0001). CONCLUSION: Gated SPECT with perfusion tracers can reliably differentiate pseudo-paradoxical from true paradoxical septal motion in patients with previous CABG, and it may be the method of choice for evaluating left ventricular performance in this patient population.

Nodal staging in localized melanoma. The experience of the Brescia Melanoma Unit.

BACKGROUND AND OBJECTIVES: We report our experience with patients affected by cutaneous melanoma undergoing sentinel node (SN) biopsy. METHODS: From November 1997 to October 2000 we performed 128 selective lymphadenectomies (SN biopsy) on 127 patients with cutaneous melanoma with Breslow thickness>1 mm or regression or ulceration. Age, sex, tumour location ad histology were recorded. RESULTS: Two hundred and thirty eight SNs were identified by lymphoscintigraphy in 167 lymphatic stations, 236 of them were identified intraoperatively using a gamma probe and patent blue V injection. Twenty-one patients had SNs with melanoma metastases (15.8%), 12 patients in the groin, eight patients in the axilla and one patient in the neck. After therapeutic lymphadenectomy eight more lymph nodes with metastases of melanoma were found in the specimens of three patients. After a follow-up ranging from 10 to 56 months the results are that 111 patients are free of disease. Ten patients died. Three patients have visceral metastases and are alive. One patient has developed two more melanomas. One patient was lost to follow-up. CONCLUSIONS: Our data confirm the clinical reliability of the SN technique in melanoma; for optimisation of the therapeutic strategy, this technique might be considered the standard method of nodal staging in the evaluation of melanoma patients.