Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer

Background: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. Methods: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. Results: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. Conclusions: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. Trial registration: ClinicalTrials.gov NCT0058827

Pore-water geochemistry of two contrasting brine-charged seep sites in the northern Gulf of Mexico continental slope

National Science Foundation; Shelf Slope Experimental Taphonomy Initiative (SSETI)Two brine-charged sites (GB425 and GC233) at the northern Gulf of Mexico (GOM) continental slope were studied for their pore-water advective flow rates and stable carbon isotope geochemistry. Using chloride as a conservative tracer, a pore-water diffusion-advection model suggests that advection dominates pore-water flow in the upper 17 cm sediments at both sites. Moreover, modeled results indicate that there is a downward pore-water flow in GB425 and an upward one in GC233, presumably caused by nearby brine-seep activities. Profiles of pore-water solutes (dissolved inorganic carbon, or DIC, sulfate, and ammonium) can be largely explained by conservative mixing between bottom water and underlying brines, which contain dissolved species that are produced at or below a subsurface reaction front, where sulfate reduction coupled with organic carbon oxidation occurs. Stable carbon isotope data indicate that organic carbon being remineralized has a similar delta(13)C value (-40 to -60%.) as that of thermogenic and biogenic methane found in this area. However, without further evidence, the exact carbon source and reaction pathway remain unclear. (c) 2009 Elsevier B.V. All rights reserved

Geochemical environments of continental shelf-upper slope sediments in the northern Gulf of Mexico

National Science Foundation; National Undersea Research ProgramGeochemical environments were characterized for 14 sites along the northern Gulf of Mexico continental shelf and upper slope, in an effort to examine the relationship between sediment geochemistry and carbonate shell taphonomy in a long-term study Shelf and Slope Experimental Taphonomy Initiative (SSETI). Three groups of environments of preservation (seep, near-seep, and shelf-and-slope) were identified based on their geochemical characteristics (i.e., oxygen uptake rate and penetration depth, pore-water saturation states, and carbonate dissolution fluxes). Diffusive oxygen uptake rate increased in the order of shelf-and-slope, near-seep, and seep, although carbonate dissolution flux did not show significant correlation with O(2) flux, presumably due to non-diffusive behavior at some sites. Using pore-water saturation indices with respect to aragonite and calcite and sedimentation rates, we defined a semi-quantitative parameter, carbonate dissolution index (CDI), to predict carbonate preservation potential during the taphonomic processes. Our limited database suggests that both the seep and the shelf-and-slope sediments may have higher carbonate preservation potential than the near-seep sediments. (C) 2011 Elsevier B.V. All rights reserved

Different Strategies for Reducing Intestinal Background Radioactivity Associated with Imaging HSV1- tk

One limitation of HSV1- tk reporter positron emission tomography (PET) with nucleoside analogues is the high background radioactivity in the intestine. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to the high radioactivity levels in the bowel, and therefore explored different strategies to increase fecal elimination of radiotracer. Intestinal radioactivity was assessed by in vivo microPET imaging and ex vivo tissue sampling following intravenous injection of 18 F-FEAU, 124 I-FIAU, or 18 F-FHBG in a germ-free mouse strain. We also explored the use of an osmotic laxative agent and/or a 100% enzymatically hydrolyzed liquid diet. No significant differences in intestinal radioactivity were observed between germ-free and normal mice. 18 F-FHBG-derived intestinal radioactivity levels were higher than those of 18 F-FEAU and 124 I-FIAU; the intestine to blood ratio was more than 20-fold higher for 18 F-FHBG than for 18 F-FEAU and 124 I-FIAU. The combination of Peptamen and Nulytely lowered intestinal radioactivity levels and increased (2.2-fold) the HSV1- tk transduced xenograft to intestine ratio for 18 F-FEAU. Intestinal bacteria in germ-free mice do not contribute to the high intestinal levels of radioactivity following injection of radionucleoside analogues. The combination of Peptamen and Nulytely increased radiotracer elimination by increasing bowel motility without inducing dehydration

Molecular Imaging Reveals Skeletal Engraftment Sites of Transplanted Bone Marrow Cells

Molecular imaging holds great promise for the in vivo study of cell therapy. Our hypothesis was that multimodality molecular imaging can identify the initial skeletal engraftment sites post-bone marrow cell transplantation. Utilizing a standard mouse model of bone marrow (BM) transplantation, we introduced a combined bioluminescence (BLI) and positron emission tomography (PET) imaging reporter gene into mouse bone marrow cells. Bioluminescence imaging was used for monitoring serially the early in vivo BM cell engraftment/expansion every 24 h. Significant cell engraftment/expansion was noted by greatly increased bioluminescence about 1 week posttransplant. Then PET was applied to acquire three-dimensional images of the whole-body in vivo biodistribution of the transplanted cells. To localize cells in the skeleton, PET was followed by computed tomography (CT). Co-registration of PET and CT mapped the sites of BM engraftment. Multiple, discrete BM cell engraftment sites were observed. Taken together, this multimodality approach may be useful for further in vivo characterization of various therapeutic cell types

Pharmacokinetic Assessment of the Uptake of 16 beta-F-18-Fluoro-5 alpha-Dihydrotestosterone (FDHT) in Prostate Tumors as Measured by PET

The aim of this study was to develop a clinically applicable non-invasive method to quantify changes in androgen receptor (AR) levels based on F-18-16 beta-fluoro-5 alpha-dihydrotestosterone (F-18-FDHT) PET in prostate cancer patients undergoing therapy. Methods: Thirteen patients underwent dynamic F-18-FDHT PET over a selected tumor. Concurrent venous blood samples were acquired for blood metabolite analysis. A second cohort of 25 patients injected with F-18-FDHT underwent dynamic PET of the heart. These data were used to generate a population-based input function, essential for pharmacokinetic modeling. Linear compartmental pharmacokinetic models of increasing complexity were tested on the tumor tissue data. Four suitable models were applied and compared using the Bayesian information criterion (BIC). Model 1 consisted of an instantaneously equilibrating space, followed by a unidirectional trap. Models 2a and 2b contained a reversible space between the instantaneously equilibrating space and the trap, into which metabolites were excluded (2a) or allowed (2b). Model 3 built on model 2b with the addition of a second reversible space preceding the unidirectional trap and from which metabolites were excluded. Results: the half-life of the F-18-FDHT in blood was between 6 and 7 min. As a consequence, the uptake of F-18-FDHT in prostate cancer lesions reached a plateau within 20 min as the blood-borne activity was consumed. Radiolabeled metabolites were shown not to bind to ARs in in vitro studies with CWR22 cells. Model 1 produced reasonable and robust fits for all datasets and was judged best by the BIC for 16 of 26 tumor scans. Models 2a, 2b, and 3 were judged best in 7, 2, and 1 cases, respectively. Conclusion: Our study explores the clinical potential of using F-18-FDHT PET to estimate free AR concentration. This process involved the estimation of a net uptake parameter such as the k(trap) of model 1 that could serve as a surrogate measure of AR expression in met-astatic prostate cancer. Our initial studies suggest that a simple body mass-normalized standardized uptake value correlates reasonably well to model-based k(trap) estimates, which we surmise may be proportional to AR expression. Validation studies to test this hypothesis are underway.Memorial Sloan-Kettering CenterMem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USAMem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USASt Lukes Roosevelt Hosp, Dept Radiol, New York, NY 10025 USAMem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USAUniversidade Federal de São Paulo, Dept Radiol, São Paulo, BrazilStanford Univ, Dept Radiol & Bioengn, Bio X Program, Stanford, CA 94305 USAUniversidade Federal de São Paulo, Dept Radiol, São Paulo, BrazilMemorial Sloan-Kettering Center: P50-CA92629Memorial Sloan-Kettering Center: P50 CA086438Memorial Sloan-Kettering Center: K23: CA102544Web of Scienc