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-NOTA-CHSg and -CHSg Labeled Microspheres for Lung Perfusion and Liver Radiomicrospheres Therapy Planning

DOI: 10.1155/2013/279872

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Abstract:

Fast biodegradable (12?h < half-life < 48?h) radioactive labeled microspheres are needed for PET and SPECT lung perfusion and radiomicrosphere therapy planning. An emulsion method was used to create 30.1 ±4.8?μm size range microspheres with biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled with or as an alternative to MAA in perfusion PET and SPECT studies. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed to increase ??in vivo stability. was labeled directly to the CHSg microspheres. Labeling yield and in vitro radiochemical stability were evaluated. In vitro CHSg microsphere degradation half-life was ~24 hours in porcine blood. Labeled microspheres were injected into Sprague Dawley rats and biodistribution was determined after 2 and 4 hours. Both -CHSg and -NOTA-CHSg were quickly allocated in the lungs after injection. -CHSg showed 91.6 ± 6.5% and 83.2 ± 4.1% of the decay corrected injected activity remaining in the lungs after 2 and 4 hours, respectively. For the obtained -NOTA-CHSg microspheres, lung allocation was very high with 98.9 ± 0.2% and 95.6 ± 0.9% after 2 and 4 hours, respectively. The addition of p-SCN-Bn-NOTA acts as a radioprotectant eliminating the released activity from the lungs to the bladder protecting the other organs. 1. Introduction Since 1974, the use of -MAA (macroaggregated albumin) has been established as the gold standard for lung perfusion studies [1]. The availability of a MAA lyophilized kit [1] and the 99Mo/ radio-isotopic generator [2] facilitated the use of -MAA as a lung perfusion agent. The orientation of macroaggregates (which are seldom spherical) in the blood flow stream is important for determining “effective size,” making it difficult to predict their in vivo behavior. Aggregates rupturing into smaller pieces add another factor making the size distribution variable and unreliable [3]. The ideal (theoretical) perfusion particle should be spherical (size not to be dependent on particle orientation) with a practical size distribution of 30 ± 10?μm [3]. Polymeric spherical microparticles with narrow size distributions have been previously obtained [4]. The use of polymerical microspheres will also eliminate the risk of disease transmission due to human derived materials (such as MAA). Another important application of -MAA is in the radiomicrosphere therapy (RMT) planning [5]. Nonspherical macroaggregates (MAA, 10–90?μm) are used to predict the distribution behavior of the perfectly spherical therapy particles used for RMT which are commercially available

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