Laurence Morandeau

Amyloid imaging results, from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging

The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimers Disease Neuroimaging Initiative (ADNI), performed (11)C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimers disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-epsilon4 carriers vs 21% in noncarriers) and increased with age, most strongly in epsilon4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in epsilon4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Abeta) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.

Detection of hypoxia with 18F-fluoromisonidazole (18F-FMISO) PET/CT in suspected or proven pancreatic cancer.

Purpose of the Report Pancreatic carcinoma is known to demonstrate molecular features of hypoxia. The aim of this prospective pilot study is to analyze the hypoxia agent fluoromisonidazole (FMISO) using PET/CT in pancreatic carcinoma and to compare FMISO activity with glucose metabolism reflected by FDG. Patients and Methods Ten patients with pancreatic carcinoma underwent FMISO and FDG PET scans. FMISO and FDG PET/CT scans were analyzed by 2 PET physicians. Regions of interest drawn on the FDG images were transposed to the FMISO images after study coregistration. The FDG SUVmax was used to quantify metabolic activity and FMISO SUVmax and tumor-to-background (muscle) ratio to quantify hypoxia. Results Seven patients were diagnosed with pancreatic adenocarcinoma. The remaining patients had a neuroendocrine tumor, poorly differentiated/sarcomatoid carcinoma, and mucinous neoplasm. Visual analysis demonstrated increased FMISO activity in 2 pancreatic adenocarcinomas. All patients, however, had increased FDG activity at the tumor site. Mean FDG SUVmax was 6 (range: 3.8 to 9.5) compared to 2.3 for FMISO (range: 1 to 3.4). The 2 positive studies on visual analysis of FMISO did not correspond to the largest tumors, the studies with the highest FMISO or FDG SUVmax. There was no significant correlation between FMISO and FDG SUVmax values. Conclusions The hypoxia imaging agent, FMISO, demonstrates minimal activity in pancreatic tumors. If FMISO PET/CT is to be included in clinical trial protocols of hypoxia in pancreatic cancer, it would require correlation with other imaging modalities to localize the tumor and allow semiquantitative analysis.

High-Activity Radio-Iodine Labeling of Conventional and Stealth Liposomes

A new method to label preformed liposomes with high activities of radiohalogenated compounds has been developed. It uses activated esters of simple synthetic molecules that may be readily halogenated, such as Bolton-Hunter reagent (BH), and arginine-containing liposomes. BH, in the form of an activated ester, crosses the liposome membrane to react with arginine inside the liposomes, as demonstrated by thin-layer chromatography and by the fact that saline-containing liposomes, or hydrolyzed BH or the water soluble sulfo-BH afforded only marginal encapsulation yields. Under optimized conditions, between 37 and 55°C, 62 ± 4% (mean ± SD) of radiolabeled BH were consistently encapsulated in the liposomes within 30 min. In molar amounts, this corresponds to a mean of 56 nmol of BH per μmol of lipids. Based on achievable specific activity, up to 2.8 GBq of iodine-131 could be entrapped per μmol of lipids. Leakage of radioactivity was very low, with less than 5% of the encapsulated activity released within 6 days at 4°C in phosphate-buffered saline and less than 50% within 24h in human serum at 37°C. The labeling stability, and the fact that both conventional and PEGylated liposomes can be readily labeled with high doses of radioactivity, will make this technique useful for in vivo targeting applications, such as tumor detection (using iodine-123 or iodine-124) or therapy (with iodine-131 or astatine-211).

Melanoma affinity in mice and immunosuppressed sheep of [125I]N-(4-dipropylaminobutyl)-4-iodobenzamide, a new targeting agent

The increasing incidence of melanoma and the lack of effective therapy have prompted the development of new vectors, more specific to the pigmented tumor, for early detection and treatment. Targeted agents have to exhibit a rapid, high tumor uptake, long tumor retention and rapid clearance from nontarget organs. This joint work presents results obtained with a new melanoma targeting agent, [(125)I]-N-(4-dipropylaminobutyl)-4-iodobenzamide or [(125)I]BZ18. After labeling with a high specific activity, the biodistribution of the compound was investigated in two animal models, the mouse and the sheep. Melanotic tumor retention was observed lasting several days. We visualized the internalization of the agent inside the melanosomes by secondary ion mass spectroscopy imaging, we measured the affinity constants of [(125)I]BZ18 on a synthetic melanin model and we demonstrated a radiotoxic effect of this labeled agent on B16F0 melanoma cell culture due to its cellular internalization. From this work, [(125)I]BZ18 appeared a promising melanoma targeting agent in the nuclear medicine field.

Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT

OBJECTIVES Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM. MATERIALS AND METHODS Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses. RESULTS Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9-19.1), median FMISO SUVmax was 2.5 (range 1.4-3.7) and median FMISO TBR was 1.8 (1.1-2.5). There was a positive correlation between intensity of metabolic activity and hypoxia (r=0.72, p=0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity (r=0.77, p<0.001). CONCLUSION This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment.

Excitation functions of natZn(p,x) nuclear reactions with proton beam energy below 18 MeV

We measured the excitation functions of (nat)Zn (p,x) reactions up to 17.6MeV, using the stacked-foils activation technique. High-purity natural zinc (and copper) foils were irradiated with proton beams generated by an 18MeV isochronous cyclotron. Activated foils were measured using high-purity Ge gamma spectroscopy to quantify the radionuclides (61)Cu, (66)Ga, (67)Ga, and (65)Zn produced from the reactions. Thick-target integral yields were also deduced from the measured excitation functions of the produced radioisotopes. These results were compared with the published literature and were found to be in good agreement with most reports, particularly those most recently compiled.

Fluoromethylcholine PET in recurrent multifocal hepatoma

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has variable efficacy in evaluating hepatocellular carcinoma. We present a case of a new oncologic imaging tracer fluoromethylcholine (FCH), which has visualized recurrent multifocal hepatoma in a patient with a poor FDG avid hepatic tumour. The lesions demonstrated on FCH PET correlated well with the findings on CT hepatic angiography.

Novel molecular imaging in lung and pleural diseases.

Molecular imaging provides an opportunity to study biological processes in vivo. Specific molecular ‘probes’ are labelled with radioactive tracers, and imaging is carried out using either PET or gamma‐cameras. The imaging is quantitative, and therefore the activity of a specific biological process (e.g. metabolism or proliferation) can be numerically assessed, which may be important for prognosis or therapy monitoring. The use of molecular imaging may lead to the development of a ‘molecular profile’ of a disease, therefore facilitating individualization of therapy and rational treatment approaches. This review article summarizes the most commonly used molecular imaging agents and their role in lung and pleural diseases. This is a rapidly developing field as new targets and imaging probes are being developed and as their clinical roles are being established.

A pilot study of the utility of choline PET-CT in prostate cancer biochemical relapse following radical prostatectomy.

To evaluate the detection rate of positive choline PET–CT and its clinical role in assisting with management decisions and the correlation between positive choline PET–CT and clinical/pathological parameters in prostate cancer patients with biochemical relapse following radical prostatectomy.

68Ga-somatostatin analogue PET-CT: Analysis of costs and benefits in a public hospital setting

Between 2009 and 2012, 68Ga‐somatostatin analogue PET‐CT progressively replaced 111In‐octreotide scintigraphy for imaging neuroendocrine tumours in WA public hospitals due to published literature demonstrating improved diagnostic accuracy and increased availability. Despite significantly improved sensitivity and specificity, 68Ga‐somatostatin analogue PET is currently unfunded in Australia. This study sought to undertake cost analysis of the two modalities in a public hospital setting and to compare them with regard to patient factors such as imaging time and radiation dose.