Can DCE-MRI explain the heterogeneity in radiopeptide uptake imaged by SPECT in a pancreatic neuroendocrine tumor model?

Although efficient delivery and distribution of treatment agents over the whole tumor is essential for successful tumor treatment, the distribution of most of these agents cannot be visualized. However, with single-photon emission computed tomography (SPECT), both delivery and uptake of radiolabeled peptides can be visualized in a neuroendocrine tumor model overexpressing somatostatin receptors. A heterogeneous peptide uptake is often observed in these tumors. We hypothesized that peptide distribution in the tumor is spatially related to tumor perfusion, vessel density and permeability, as imaged and quantified by DCE-MRI in a neuroendocrine tumor model. Four subcutaneous CA20948 tumor-bearing Lewis rats were injected with the somatostatin-analog 111In-DTPA-Octreotide (50 MBq). SPECT-CT and MRI scans were acquired and MRI was spatially registered to SPECT-CT. DCE-MRI was analyzed using semi-quantitative and quantitative methods. Correlation between SPECT and DCE-MRI was investigated with 1) Spearman’s rank correlation coefficient; 2) SPECT uptake values grouped into deciles with corresponding median DCE-MRI parametric values and vice versa; and 3) linear regression analysis for median parameter values in combined datasets. In all tumors, areas with low peptide uptake correlated with low perfusion/density/ /permeability for all DCE-MRI-derived parameters. Combining all datasets, highest linear regression was found between peptide uptake and semi-quantitative parameters (R2>0.7). The average correlation coefficient between SPECT and DCE-MRI-derived parameters ranged from 0.52-0.56 (p<0.05) for parameters primarily associated with exchange between blood and extracellular extravascular space. For these parameters a linear relation with peptide uptake was observed. In conclusion, the ‘exchange-related’ DCE-MRI-derived parameters seemed to predict peptide uptake better than the ‘contrast amount- related’ parameters. Consequently, fast and efficient diffusion through the vessel wall into tissue is an important factor for peptide delivery. DCE-MRI helps to elucidate the relation between vascular characteristics, peptide delivery and treatment efficacy, and may form a basis to predict targeting efficiency.Imaging Science and TechnologyApplied Science

Strongyloidiasis: Really a Zoonosis?

More than 600 million people are estimated to be infected with the nematode Strongyloides stercoralis, which is often overlooked during routine parasitological diagnostics. Some of the young worms mature to infective larvae within the host, enabling this parasite to establish long-lived, self-sustaining infections. While most of these infections are mild, they can self-enhance, resulting in complicated strongyloidisas, which if not treated in time, is normally lethal. While it is undisputed that dogs are susceptible to experimental infection with human-derived S. stercoralis, it has long been debated if Strongyloides sp. naturally found in dogs are human infective S. stercoralis or belong to a different species, S. canis. Based on recent studies, I argue that dogs naturally carry S. stercoralis, in addition to at least one other species, for which we have no indication that it infects people. I argue that for all practical purposes of S. stercoralis treatment and prevention, dogs should be seriously considered as possible sources for human S. stercoralis. However, from a rigorous scientific point of view, we must admit that currently we have no idea about the relative importance of zoonotic transmission compared with human to human transmission