scholarly journals Competitive Blocking of Salivary Gland [18F]DCFPyL Uptake via Localized, Retrograde Ductal Injection of Non-radioactive DCFPyL: A Preclinical Study

2021 ◽  
Author(s):  
Jyoti Roy ◽  
Blake M Warner ◽  
Falguni Basuli ◽  
Xiang Zhang ◽  
Changyu Zheng ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Dose Range ◽  
Systemic Circulation ◽  
Preclinical Study ◽  
Dose Finding ◽  
Tumor Uptake ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Novel Approach ◽  
Dose Levels

Abstract BACKGROUNDPSMA-targeted radionuclide therapy (TRT) is a promising treatment for prostate cancer (PCa) but dose-limiting xerostomia can severely limit its clinical adaptation, especially when using alpha-emitting radionuclides. With [18F]DCFPyL as a surrogate for PSMA-TRT, we report a novel method to selectively reduce salivary gland (SG) uptake of systemically administered [18F]DCFPyL by immediate prior infusion of non-radioactive standard of [18F]DCFPyL (DCFPyL) directly into the SG via retrograde cannulation. METHODSA dose-finding cohort using athymic nude mice demonstrated proof-of-principle that SG uptake can be selectively blocked by DCFPyL administered either locally via cannulation (CAN group) or systemically (SYS group). The experiments were repeated in a validation cohort of 22RV1 tumor-bearing mice. Submandibular glands (SMG) of CAN mice were locally blocked with either saline or DCFPyL (dose range: 0.01x to 1000x molar equivalent of the radioactive [18F]DCFPyL dose). The radioactive dose of [18F]DCFPyL was administered systemically 10 minutes later and the mice euthanized after 1 hour for biodistribution studies. Toxicity studies were done at up to 1000x dose. RESULTSIn the dose-finding cohort, the SYS group showed a dose-dependent 12-40% decrease in both the SMG T:B and the kidney (tumor surrogate). Mild blocking was observed at 0.01x, with maximal blocking reached at 1x with no additional blocking up to 1000x. In the CAN group, blocking at the 0.1x and 1x dose levels resulted in a similar 42-53% decrease, but without the corresponding decrease in kidney uptake as seen in the SYS group. Some evidence of “leakage” of DCFPyL from the salivary gland into the systemic circulation was observed. However, experiments in 22RV1 tumor-bearing mice at the 0.1x and 1x dose levels confirm that, at the appropriate blocking dose, SG uptake of [18F]DCFPyL can be selectively reduced without affecting tumor uptake and with no toxicity.CONCLUSIONOur results suggest that direct retrograde instillation of DCFPyL into the SG could predictably and selectively decrease salivary uptake of systemically administered [18F]DCFPyL without altering tumor uptake, if given at the appropriate dose. This novel approach is easily translatable to clinical practice and has the potential to mitigate xerostomia, without compromising the therapeutic efficacy of the PSMA-TRT.

scholarly journals Competitive blocking of salivary gland [18F]DCFPyL uptake via localized, retrograde ductal injection of non-radioactive DCFPyL: a preclinical study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jyoti Roy ◽  
Blake M. Warner ◽  
Falguni Basuli ◽  
Xiang Zhang ◽  
Changyu Zheng ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Dose Range ◽  
Systemic Circulation ◽  
Preclinical Study ◽  
Dose Finding ◽  
Tumor Uptake ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Novel Approach ◽  
Dose Levels

Abstract Background PSMA-targeted radionuclide therapy (TRT) is a promising treatment for prostate cancer (PCa), but dose-limiting xerostomia can severely limit its clinical adaptation, especially when using alpha-emitting radionuclides. With [18F]DCFPyL as a surrogate for PSMA-TRT, we report a novel method to selectively reduce salivary gland (SG) uptake of systemically administered [18F]DCFPyL by immediate prior infusion of non-radioactive standard of [18F]DCFPyL (DCFPyL) directly into the SG via retrograde cannulation. Methods A dose-finding cohort using athymic nude mice demonstrated proof of principle that SG uptake can be selectively blocked by DCFPyL administered either locally via cannulation (CAN group) or systemically (SYS group). The experiments were repeated in a validation cohort of 22RV1 tumor-bearing mice. Submandibular glands (SMG) of CAN mice were locally blocked with either saline or DCFPyL (dose range: 0.01× to 1000× molar equivalent of the radioactive [18F]DCFPyL dose). The radioactive dose of [18F]DCFPyL was administered systemically 10 min later and the mice euthanized after 1 h for biodistribution studies. Toxicity studies were done at up to 1000× dose. Results In the dose-finding cohort, the SYS group showed a dose-dependent 12–40% decrease in both the SMG T/B and the kidney (tumor surrogate). Mild blocking was observed at 0.01× , with maximal blocking reached at 1× with no additional blocking up to 1000× . In the CAN group, blocking at the 0.1× and 1× dose levels resulted in a similar 42–53% decrease, but without the corresponding decrease in kidney uptake as seen in the SYS group. Some evidence of “leakage” of DCFPyL from the salivary gland into the systemic circulation was observed. However, experiments in 22RV1 tumor-bearing mice at the 0.1× and 1× dose levels confirm that, at the appropriate blocking dose, SG uptake of [18F]DCFPyL can be selectively reduced without affecting tumor uptake and with no toxicity. Conclusion Our results suggest that direct retrograde instillation of DCFPyL into the SG could predictably and selectively decrease salivary uptake of systemically administered [18F]DCFPyL without altering tumor uptake, if given at the appropriate dose. This novel approach is easily translatable to clinical practice and has the potential to mitigate xerostomia, without compromising the therapeutic efficacy of the PSMA-TRT.

scholarly journals Synthesis and evaluation of radiolabeled, folic acid-PEG conjugated, amino silane coated magnetic nanoparticles in tumor bearing Balb/C mice

Nukleonika ◽  
2015 ◽  
Vol 60 (3) ◽  
pp. 497-502 ◽  
Author(s):  
Javad Razjouyan ◽  
Hamidreza Zolata ◽  
Omid Khayat ◽  
Fereidoun Nowshiravan ◽  
Nami Shadanpour ◽  
...  
Keyword(s):  
Folic Acid ◽  
Folate Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Tumor Uptake ◽  
Mri Imaging ◽  
Tumor Bearing ◽  
Biodistribution Studies

Abstract To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI) imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modified superparamagnetic iron oxide nanoparticles (SPIONs) were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato) iron (III) to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl) triethoxysilane (APTES), and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG) through amine group of (3-aminopropyl) triethoxysilane. Finally, the particles were labeled with 64Cu (t1/2 = 12.7 h) using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester) DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR) overexpressing KB (established from a HeLa cell contamination) and mouse fibroblast cell (MFB) lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modification increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB). Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specific uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.

scholarly journals Unified approach for extrapolation and bridging of adult information in early-phase dose-finding paediatric studies

2016 ◽  
Vol 27 (6) ◽  
pp. 1860-1877 ◽  
Author(s):  
Caroline Petit ◽  
Adeline Samson ◽  
Satoshi Morita ◽  
Moreno Ursino ◽  
Jérémie Guedj ◽  
...  
Keyword(s):  
Early Phase ◽  
Dose Range ◽  
Dose Finding ◽  
Pharmacokinetic Data ◽  
Dose Selection ◽  
Number Of Patients ◽  
Distribution Parameters ◽  
Dose Levels ◽  
Medical Process ◽  
Unified Method

The number of trials conducted and the number of patients per trial are typically small in paediatric clinical studies. This is due to ethical constraints and the complexity of the medical process for treating children. While incorporating prior knowledge from adults may be extremely valuable, this must be done carefully. In this paper, we propose a unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults. The dose-range is calculated under three extrapolation options, linear, allometry and maturation adjustment, using adult pharmacokinetic data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose–toxicity and dose–efficacy relationships are obtained using early-phase adult toxicity and efficacy data at several dose levels. Priors are integrated into the dose-finding process through Bayesian model selection or adaptive priors. This calibrates the model to adjust for misspecification, if the adult and pediatric data are very different. We performed a simulation study which indicates that incorporating prior adult information in this way may improve dose selection in children.

Copper-64 labeled sulfophthalocyanines for positron emission tomography (PET) imaging in tumor-bearing rats

2008 ◽  
Vol 12 (01) ◽  
pp. 49-53 ◽  
Author(s):  
Anton Soucy-Faulkner ◽  
Jacques A. Rousseau ◽  
Réjean Langlois ◽  
Véronique Berard ◽  
Roger Lecomte ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Photodynamic Therapy ◽  
Emission Tomography ◽  
Tumor Uptake ◽  
Tissue Samples ◽  
Metal Free ◽  
Tumor Bearing ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Tumor Selectivity

Sulfonated metallophthalocyanines ( PcS ) are second generation photosensitizers for photodynamic therapy (PDT) of cancer. Metal-free H 2 PcS are readily labeled with 64 Cu ++ to yield a mixture of sulfonated [64 Cu ] CuPcS suitable for biodistribution studies in tumor-bearing rats by positron emission tomography (PET). Most of the 64 Cu activity was sequestrated within the kidneys (20%ID/g) and liver (12%ID/g) while tumor uptake values remained low (0.2%ID/g). Dissection and counting of individual tissue samples after the 24 h scan confirmed the uptake values derived from the PET images. The procedure can be applied to series of novel PcS to evaluate structure-tumor selectivity relationships as a parameter to select potential agents for photodynamic therapy.

scholarly journals Biological behavior of a new 68Ga-labelled glucose derivative as a potential agent for tumor imaging

2021 ◽  
Vol 2058 (1) ◽  
pp. 012037
Author(s):  
V K Tishchenko ◽  
V M Petriev ◽  
K A Kuzenkova ◽  
I N Zavestovskaya ◽  
P V Shegai ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
Biological Behavior ◽  
Tumor Uptake ◽  
Aseptic Inflammation ◽  
Promising Alternative ◽  
Tumor Bearing ◽  
Pet Tracer ◽  
Biodistribution Studies ◽  
Positron Emitter ◽  
Glucose Derivative

Abstract Glucose analogs and derivatives labeled with positron emitter 68Ga are considered to be a promising alternative to widely used radiotracer 18F-FDG for tumor PET imaging. In this study a biodistribution of a new glucose derivative labeled with 68Ga (68Ga-NODA-thioglucose) was investigated. All biodistribution studies were carried out in Balb/c mice with experimental model of tumor or aseptic inflammation. The tumor uptake of 68Ga-NODA-TG decreased throughout the study from 3.00±0.08 % ID/g to 1.06±0.04 %ID/g. The peak amount of 68Ga-NODA-TG in muscle with inflammation reached 4.33±0.12 % ID/g, decreasing to 0.23±0.08 % ID/g. In other organs and tissues the biodistribution of 68Ga-NODA-TG was similar in tumor-bearing mice and mice with aseptic inflammation. In conclusion, the obtained results suggest that 68Ga-NODA-TG has the potential for clinical application as a PET tracer.

A Novel Approach for the Treatment of Sialolithiasis that Preserves Salivary Duct Anatomy

2021 ◽  
pp. 000348942110189
Author(s):  
Gani Atilla Şengör ◽  
Ahmet Mert Bilgili
Keyword(s):  
Salivary Gland ◽  
Success Rate ◽  
Cost Effective ◽  
Complete Removal ◽  
Level Of Evidence ◽  
Invasive Approach ◽  
Pneumatic Lithotripsy ◽  
Novel Approach ◽  
Surgical Methods ◽  
Salivary Gland Stones

Objective: The sialendoscopy era in the treatment of salivary gland stones has reduced the use of classical surgical methods. However, the miniature ducts and tools may cause difficulties in removing large sialoliths. Therefore, invasive combined oral surgeries or gland resection may be considered. We searched for the most suitable method in order to stay in line with the minimally invasive approach that preserves the ductus anatomy, and that can reduce the surgical fears of patients. Materials and Methods: The study included 84 cases (23 parotid and 61 submandibular) in whom stones were fragmented by pneumatic lithotripsy and removed between January 2015 and January 2020. The parotid cases comprised 7 females and 16 males, and the submandibular cases comprised 25 females and 36 males. Intraductal lithotripsy was performed using pneumatic lithotripter. This study has fourth level of evidence. Results: Based on total number of cases (n = 84), success rate was 67/84 (79.7%) immediately after sialendoscopy, and overall success rate was 77/84 (91.6%). Based on number of stones treated (n = 111), our immediate success rate was 94/111 (84.6%), and overall success rate was 104/111 (93.7%). The success criteria were complete removal of the stone and fragments in a single sialendoscopy procedure and resolution of symptoms. Conclusions: We successfully treated salivary gland stones, including L3b stones, in our patient cohort with sialendoscopy combined with pneumatic lithotripsy. The lithotripsy method that we have adapted seems to be more useful and cost-effective compared to its alternatives. We were also able to preserve the ductus anatomy and relieve patients’ concerns. Level of Evidence: Level IV

scholarly journals Design of PSMA ligands with modifications at the inhibitor part: an approach to reduce the salivary gland uptake of radiolabeled PSMA inhibitors?

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Veronika Barbara Felber ◽  
Manuel Amando Valentin ◽  
Hans-Jürgen Wester
Keyword(s):  
Salivary Gland ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
In Vivo Studies ◽  
Tumor Xenograft ◽  
Tumor Uptake ◽  
Lncap Cells ◽  
High Affinity

Abstract Aim To investigate whether modifications of prostate-specific membrane antigen (PSMA)-targeted radiolabeled urea-based inhibitors could reduce salivary gland uptake and thus improve tumor-to-salivary gland ratios, several analogs of a high affinity PSMA ligand were synthesized and evaluated in in vitro and in vivo studies. Methods Binding motifs were synthesized ‘on-resin’ or, when not practicable, in solution. Peptide chain elongations were performed according to optimized standard protocols via solid-phase peptide synthesis. In vitro experiments were performed using PSMA+ LNCaP cells. In vivo studies as well as μSPECT/CT scans were conducted with male LNCaP tumor xenograft-bearing CB17-SCID mice. Results PSMA ligands with A) modifications within the central Zn2+-binding unit, B) proinhibitor motifs and C) substituents & bioisosteres of the P1′-γ-carboxylic acid were synthesized and evaluated. Modifications within the central Zn2+-binding unit of PSMA-10 (Glu-urea-Glu) provided three compounds. Thereof, only natLu-carbamate I (natLu-3) exhibited high affinity (IC50 = 7.1 ± 0.7 nM), but low tumor uptake (5.31 ± 0.94% ID/g, 1 h p.i. and 1.20 ± 0.55% ID/g, 24 h p.i.). All proinhibitor motif-based ligands (three in total) exhibited low binding affinities (> 1 μM), no notable internalization and very low tumor uptake (< 0.50% ID/g). In addition, four compounds with P1′-ɣ-carboxylate substituents were developed and evaluated. Thereof, only tetrazole derivative natLu-11 revealed high affinity (IC50 = 16.4 ± 3.8 nM), but also this inhibitor showed low tumor uptake (3.40 ± 0.63% ID/g, 1 h p.i. and 0.68 ± 0.16% ID/g, 24 h p.i.). Salivary gland uptake in mice remained at an equally low level for all compounds (between 0.02 ± 0.00% ID/g and 0.09 ± 0.03% ID/g), wherefore apparent tumor-to-submandibular gland and tumor-to-parotid gland ratios for the modified peptides were distinctly lower (factor 8–45) than for [177Lu]Lu-PSMA-10 at 24 h p.i. Conclusions The investigated compounds could not compete with the in vivo characteristics of the EuE-based PSMA inhibitor [177Lu]Lu-PSMA-10. Although two derivatives (3 and 11) were found to exhibit high affinities towards LNCaP cells, tumor uptake at 24 h p.i. was considerably low, while uptake in salivary glands remained unaffected. Optimization of the established animal model should be envisaged to enable a clear identification of PSMA-targeting radioligands with improved tumor-to-salivary gland ratios in future studies.

Phase I Dose-Finding Study of Weekly Single-Agent Patupilone in Patients With Advanced Solid Tumors

2005 ◽  
Vol 23 (36) ◽  
pp. 9120-9129 ◽  
Author(s):  
Eric H. Rubin ◽  
John Rothermel ◽  
Fisseha Tesfaye ◽  
Tianling Chen ◽  
Martine Hubert ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Half Life ◽  
Drug Exposure ◽  
Dose Range ◽  
Single Agent ◽  
Dose Finding ◽  
Advanced Solid Tumors ◽  
Blood Concentrations ◽  
Terminal Half Life

Purpose To evaluate the safety and maximum-tolerated dose (MTD) of weekly patupilone, a natural epothilone B, in patients with advanced solid tumors. Patients and Methods Patients were treated with patupilone (0.3 to 3.6 mg/m2) for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities (DLTs), MTD, and pharmacokinetics were determined for each schedule of administration. Results Ninety-one patients were enrolled. The most common tumor types included ovarian, breast, and colon cancers. Doses of patupilone less than 2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off schedule were tolerated well. At higher doses, DLTs were observed using both dosing schedules, with diarrhea the most common DLT. The MTD for both treatment schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations declined in a multiphasic manner with a terminal half-life of 4 days. Drug clearance was nonrenal and was not related to body-surface area. Over the dose range evaluated, systemic drug exposure was approximately dose proportional. Three patients achieved a partial response, and 31 patients had stable disease. Two patients experiencing a partial response had received prior taxane therapy. Conclusion Patupilone is well tolerated when administered at a dose of 2.5 mg/m2, using either a 6 weeks on/3 weeks off or a 3 weeks on/1 week off schedule. In contrast with murine studies, patupilone has a relatively prolonged terminal half-life in humans. The partial responses in patients previously treated with taxanes is consistent with promising preclinical results.

Phase I study of spirogermanium given daily.

1983 ◽  
Vol 1 (5) ◽  
pp. 331-336 ◽  
Author(s):  
S S Legha ◽  
J A Ajani ◽  
G P Bodey
Keyword(s):  
Continuous Infusion ◽  
Tumor Regression ◽  
Dose Range ◽  
Maximum Tolerated Dose ◽  
Optimum Dose ◽  
Second Phase ◽  
Clinical Effects ◽  
Third Phase ◽  
Dose Levels ◽  
Dose Limiting Toxicity

Spirogermanium, an azaspirane compound, has recently had limited clinical trials using a schedule of intravenous injection one to three times every week. The observation of clinical antitumor activity and lack of myelosuppression prompted us to investigate further the clinical effects of spirogermanium administered on various schedules. A total of 52 patients with advanced metastatic tumors refractory to standard therapy were treated with spirogermanium. Three different schedules of drug administration were evaluated. Initially, a short daily IV infusion for 5 days every week was evaluated, starting with a dose of 30 mg/m2/day. A total of 22 patients received 69 courses with a dose range of 30-120 mg/m2/day for 5 days every week. The maximum tolerated dose was 100 mg/m2/day IV over 1 hr and 120 mg/m2 over 2-3 hr. In the second phase of the study, 12 patients received 41 courses of spirogermanium as a 24-hr continuous infusion for 5 days/wk at a dose of 150-375 mg/m2/day. The maximum tolerated dose was 200 mg/m2/day for 5 days. In the third phase of the study, 18 patients received spirogermanium as a continuous infusion daily for a median of 30 days (range 6-77 days) in a dose range of 100-200 mg/m2/day. The maximum tolerated dose was 150 mg/m2/day. Of the 44 assessable patients, 3 demonstrated a partial response and 3 had minor tumor regression; all responses occurred in lymphoma patients. The dose-limiting toxicity of spirogermanium was neurologic; other side effects consisted of mild anorexia, nausea and vomiting, and possible lung toxicity. There was no clear evidence of cumulative toxicity despite daily administration of spirogermanium. Our data suggest that spirogermanium can be administered daily by several different schedules, and the optimum dose depends on the infusion time and the duration of therapy. The delivery of drug by continuous infusion permitted administration of twofold higher dose levels compared to the standard IV schedules used in previous studies.

scholarly journals 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

2018 ◽  
Vol 21 (1s) ◽  
pp. 32s-47s ◽  
Author(s):  
Hans-Soenke Jans ◽  
Xiao-Hong Yang ◽  
Dion R Brocks ◽  
Piyush Kumar ◽  
Melinda Wuest ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Blood Sampling ◽  
Tumor Uptake ◽  
Blood Samples ◽  
Non Invasive ◽  
Tumor Bearing ◽  
Positron Emission ◽  
18F Fdg ◽  
Derived Data

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 (t½) 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’s 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. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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