{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:03:54Z","timestamp":1790510634316,"version":"4.1.0"},"reference-count":0,"publisher":"Frontiers Media SA","issue":"1s","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharm Pharm Sci"],"abstract":"<jats:p>Purpose: Pharmacokinetic (PK) data are generally derived from blood samples withdrawn serially over a defined period after dosing. In small animals, blood sampling after dosing presents technical difficulties, particularly when short time intervals and frequent sampling are required. Positron emission tomography (PET) is a non-invasive functional imaging technique that can provide semi-quantitative temporal data for defined volume regions of interest (vROI), to support kinetic analyses in blood and other tissues. The application of preclinical small-animal PET to determine and compare PK parameters for [18F]FDG and [18F]FAZA, radiopharmaceuticals used clinically for assessing glucose metabolism and hypoxic fractions, respectively, in the same mammary EMT6 tumor-bearing mouse model, is reported here. Methods: Two study groups were used: normal BALB\/c mice under isoflurane anesthesia were intravenously injected with either [18F]FDG or [18F]FAZA. For the first group, blood-sampling by tail artery puncture was used to collect blood samples which were then analyzed with Radio-microTLC. Dynamic PET experiments were performed with the second group of mice and analyzed for blood input function and tumor uptake utilizing a modified two compartment kinetic model. Heart and inferior vena cava vROIs were sampled to obtain image-derived data. PK parameters were calculated from blood samples and image-derived data. Time-activity curves (TACs) were also generated over regions of liver, kidney and urinary bladder to depict clearance profiles for each radiotracer. Results: PK values generated by classical blood sampling and PET image-derived analysis were comparable to each other for both radiotracers. Heart vROI data were suitable for analysis of [18F]FAZA kinetics, but metabolic uptake of radioactivity mandated the use of inferior vena cava vROIs for [18F]FDG analysis. While clearance (CL) and blood half-life (t\u00bd) were similar for both [18F]FDG and [18F]FAZA for both sampling methods, volume of distribution yielded larger differences, indicative of limitations such as partial volume effects within quantitative image-derived data. [18F]FDG underwent faster blood clearance and had a shorter blood half-life than [18F]FAZA. Kinetic analysis of tumor uptake from PET image data showed higher uptake and longer tumor tissue retention of [18F]FDG, indicative of the tumor\u2019s glucose metabolism rate, versus lower tumor uptake and retention of [18F]FAZA. While [18F]FAZA possesses a somewhat greater hepatobiliary clearance , [18F]FDG clears faster through the renal system which results in faster radioactivity accumulation in the urinary bladder. Conclusions: The present study provides a working example of the applicability of functional PET imaging as a suitable tool to determine PK parameters in small animals. The comparative analysis in the current study demonstrates that it is feasible to use [18F]FDG PET and [18F]FAZA PET in the same model to analyze their blood PK parameters, and to estimate kinetic parameters for these tracers in tumor. This non-invasive imaging-based determination of tissue kinetic parameters facilitates translation from pre-clinical to clinical phases of drug development.\u00a0This article is open to POST-PUBLICATION REVIEW. Registered readers (see \u201cFor Readers\u201d) may comment by clicking on ABSTRACT on the issue\u2019s contents page.<\/jats:p>","DOI":"10.18433\/jpps29788","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T01:41:45Z","timestamp":1524015705000},"page":"32s-47s","source":"Crossref","is-referenced-by-count":12,"title":["Positron Emission Tomography (PET) and Pharmacokinetics: Classical Blood Sampling Versus Image-Derived Analysis of [18F]FAZA and [18F]FDG in a Murine Tumor Bearing Model"],"prefix":"10.3389","volume":"21","author":[{"given":"Hans-Soenke","family":"Jans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dion R","family":"Brocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Wuest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard I","family":"Wiebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,4,22]]},"container-title":["Journal of Pharmacy &amp; Pharmaceutical Sciences"],"original-title":[],"link":[{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/download\/29788\/21410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/download\/29788\/21410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T13:35:30Z","timestamp":1673616930000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/view\/29788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,22]]},"references-count":0,"journal-issue":{"issue":"1s","published-online":{"date-parts":[[2018,3,30]]}},"URL":"https:\/\/doi.org\/10.18433\/jpps29788","relation":{},"ISSN":["1482-1826","1482-1826"],"issn-type":[{"value":"1482-1826","type":"electronic"},{"value":"1482-1826","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4,22]]}}}