Objectives-18 F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose from 18 F-HX4 using whole body PET/CT scans in monkeys and humans.Methods-Successive whole body PET/CT scans were performed following the injection of 18 F-HX4 to four healthy humans (422 ± 142 MBq) and to three rhesus monkeys (189 ± 3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software.Results-The bladder, liver and kidneys show the highest percentage of the injected radioactivity for humans and monkeys. For humans about 45% of the activity is eliminated by bladder voiding in 3.6 hours, and for monkeys 60% is in the bladder content after 3.0 hours. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415 ± 18 μGy/MBq (monkeys) and 299±38 μGy/MBq (humans), in the 4.8 hour bladder voiding interval model. The average value of effective dose (ED) for the adult male was estimated at 42 ± 4.2 μSv/ MBq from monkey data and 27 ± 2 μSv/MBq from human data.
Activated macrophages play a significant role in initiation and progression of inflammatory diseases and may serve as the basis for the development of targeted diagnostic methods for imaging sites of inflammation. Folate receptor beta (FR-β) is differentially expressed on activated macrophages associated with inflammatory disease states yet is absent in either quiescent or resting macrophages. Because folate binds with high affinity to FR-β, development of folate directed imaging agents has proceeded rapidly in the past decade. However, reports of PET based imaging agents for use in inflammatory conditions remain limited. To investigate whether FR-β expressing macrophages could be exploited for PET based inflammatory imaging, two separate folate-targeted PET imaging agents were developed, 4-[(18)F]-fluorophenylfolate and [(68)Ga]-DOTA-folate, and their ability to target activated macrophages were examined in a rodent inflammatory paw model. We further compared inflamed tissue uptake with 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]-FDG). microPET analysis demonstrated that both folate-targeted PET tracers had higher uptake in the inflamed paw compared to the control paw. When these radiotracers were compared to [(18)F]-FDG, both folate PET tracers had a higher signal-to-noise ratio (SNR) than [(18)F]-FDG, suggesting that folate tracers may be superior to [(18)F]-FDG in detecting diseases with an inflammatory component. Moreover, both folate-PET imaging agents also bind to FR-α which is overexpressed on multiple human cancers. Therefore, these folate derived PET tracers may also find use for localizing and staging FR(+) cancers, monitoring response to therapy, and for selecting patients for tandem folate-targeted therapies.
In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female.
Annexin A5 has been used for the detection of apoptotic cells, due to its ability to bind to phosphatidylserine (PS). Four different labeled Annexin A5 adducts were evaluated in rhesus monkey, with radiolabeling achieved via 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Of these adducts differing conjugation methods were employed which resulted in nonspecific radiolabeling (AxA5-I), or site-specific radiolabeling (AxA5-II). A nonbinding variant of Annexin A5 was also evaluated (AxA5-IINBV), conjugation here was site specific. The fourth adduct examined had both specific and nonspecific conjugation techniques employed (AxA5-IImDOTA). Blood clearance for each adduct was comparable, while appreciable uptake was observed in kidney, liver, and spleen. Significant differences in uptake of AxA5-I and AxA5-II were observed, as well as between AxA5-II and AxA5-IINBV. No difference between AxA5-II and AxA5-IImDOTA was observed, suggesting that conjugating DOTA nonspecifically did not affect the in vivo biodistribution of Annexin A5.
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