Ga68-NOTA-CHSg and Tc99m-CHSg Labeled Microspheres for Lung Perfu

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 99mTc or 68Ga 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 68Ga in vivo stability. 99mTc 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 99mTc-CHSg and 68Ga-NOTA-CHSg were quickly allocated in the lungs after injection. 99mTc-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 68Ga-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 68Ga activity from the lungs to the bladder protecting the other organs.

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…Significant corrections are required in order to accurately image these isotopes especially for quantitative 3D PET where the potential for spurious coincidence contamination is much increased. Other efforts into using biodegradable Chitosan glycol MS labeled to 68 Ga have been developed in preclinical models [132], although no clinical results are yet available.…”

68Ga‐Ca‐phytate particles: A potential lung perfusion agent of synthetic origin prepared in a cold kit format

“…To abate this type of risk, researchers have pursued alternative agents within the research and development domain, aiming to achieve the shortest translation path into the clinic but without compromising on radiopharmaceutical quality and safety. Some of the experimental lung perfusion particulate agents include the following: 67 Ga‐DTPA/ETDA‐microspheres, 68 Ga‐DTPA‐microspheres, 99m Tc‐hydrolyzed ( h )‐SnF 2 “larger” colloid, 86 Y‐DOTA‐HSA‐microspheres, 68 Ga‐NOTA‐CHSg‐microspheres, and 68 Ga‐MAA or 68 Galligas for ventilation only . The 68 Ga‐based agents have gained traction more recently since the wide availability of a 68 Ge/ 68 Ga‐generator, and these have provided high‐quality diagnostic positron emission tomography (PET) images.…”