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Despite decades of efforts, non-invasive sensitive detection of small malignant brain tumors still remains challenging. Here we report a dual-modality (124)I-labeled gold nanostar ((124)I-GNS) probe for sensitive brain tumor imaging with positron emission tomography (PET) and subcellular tracking with two-photon photoluminescence (TPL) and electron microscopy (EM). Experiment results showed that the developed nanoprobe has potential to reach sub-millimeter intracranial brain tumor detection using PET scan, which is superior to any currently available non-invasive imaging modality. Microscopic examination using TPL and EM further confirmed that systemically administered GNS nanoparticles permeated the brain tumor leaky vasculature and accumulated inside brain tumor cells following systemic administration. Selective brain tumor targeting by enhanced permeability and retention (EPR) effect and ultrasensitive imaging render (124)I-GNS nanoprobe promise for future brain tumor-related preclinical and translational applications.

Radionuclides conjugated to molecules that bind specifically to cancer cells are of great interest as a means to increase the specificity of radiotherapy. Currently, the methods to disseminate these targeted radiotherapeutics have been either systemic delivery or by bolus injection into the tumor or tumor resection cavity. Herein we model a potentially more efficient method of delivery, namely pressure-driven fluid flow, called convection-enhanced delivery (CED), where a device infuses the molecules in solution (or suspension) directly into the tissue of interest. In particular, we focus on the setting of primary brain cancer after debulking surgery, where the tissue margins surrounding the surgical resection cavity are infiltrated with tumor cells and the most frequent sites of tumor recurrence. We develop the combination of fluid flow, chemical kinetics, and radiation dose models needed to examine such protocols. We focus on Auger electron-emitting radionuclides (e.g. 67Ga, 77Br, 111In, 125I, 123I, 193mPt, 195mPt) whose short range makes them ideal for targeted therapy in this setting of small foci of tumor spread within normal tissue. By solving these model equations, we confirm that a CED protocol is promising in allowing sufficient absorbed dose to destroy cancer cells with minimal absorbed dose to normal cells at clinically feasible activity levels. We also show that Auger emitters are ideal for this purpose while the longer range alpha particle emitters fail to meet criteria for effective therapy (as neither would energetic beta particle emitters). The model is used with simplified assumptions on the geometry and homogeneity of brain tissue to allow semi-analytic solutions to be displayed, and with the purpose of a first examination of this new delivery protocol proposed for radionuclide therapy. However, we emphasize that it is immediately extensible to personalized therapy treatment planning as we have previously shown for conventional CED, at the price of requiring a fully numerical computerized approach.

Radionuclides such as 211At and 212Bi which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of 212Bi and 211At alpha-particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the beta-particles emitted by radionuclides such as 131I and 90Y, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with 212Bi- and 211At-labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of alpha-emitting radiopharmaceuticals is meta-[211At]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [3H]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[131I] iodobenzylguanidine. For meta-[211At] astatobenzylguanidine, the Do value was equivalent to only 6-7 211At atoms bound per cell. These results suggest that meta-[211At] astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

The objective of this investigation was to evaluate small-field-of-view, ultra-high-resolution pinhole collimation for a rotating-camera SPECT system that could be used to image small laboratory animals. Pinhole collimation offers distinct advantages over conventional parallel-hole collimation when used to image small objects. Since geometric sensitivity increases markedly for points close to the pinhole, small-diameter and high-magnification pinhole geometries may be useful for selected imaging tasks when used with large-field-of-view scintillation cameras. The use of large magnifications can minimize the loss of system resolution caused by the intrinsic resolution of the scintillation camera. A pinhole collimator has been designed and built that can be mounted on one of the scintillation cameras of a triple-head SPECT system. Three pinhole inserts with approximate aperture diameters of 0.6, 1.2 and 2.0 mm have been built and can be mounted individually on the collimator housing. When a ramp filter is used with a three-dimensional (3D) filtered backprojection (FBP) algorithm, the three apertures have in-plane SPECT spatial resolutions (FWHM) at 4 cm of 1.5, 1.9 and 2.8 mm, respectively. In-air point source sensitivities at 4 cm from the apertures are 0.9, 2.6 and 5.7 counts s(-1) microCi(-1) (24, 70 and 154 counts s(-1) MBq(-1)) for the 0.6, 1.2 and 2.0 mm apertures, respectively. In vitro image quality was evaluated with a micro-cold-rod phantom and a micro-Defrise phantom using both the 3D FBP algorithm and a 3D maximum likelihood-expectation maximization (ML-EM) algorithm. In vivo image quality was evaluated using two (315 and 325 g) rats. Ultra-high-resolution pinhole SPECT is an inexpensive and simple approach for imaging small animals that can be used with existing rotating-camera SPECT system.

The authors have investigated standard SPECT techniques (rotating gamma cameras, multi-hole collimators, and filtered backprojection reconstruction) for imaging astatine-211 distributions. Since 211At emits alpha particles, this nuclide has potential for use in radiotherapy. The capability of imaging this nuclide would allow in vivo evaluation of the distribution and stability of potential 211At-labelled radiotherapeutic agents. 211At decay yields X-rays in the 77-92 keV range in addition to 500-900 keV gamma rays. The study evaluates the feasibility of SPECT imaging using the X-ray emissions of 211At. The authors have evaluated several collimators, with the determination that the medium-energy collimators are suitable, with 7% penetration (uncollimated counts versus collimated counts). Several phantoms were imaged and attenuation coefficients were measured (narrow-beam mu =0.182 cm-1 for 77-80 keV X-rays in water).