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Abstract: Introduction: It is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [18F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [18F]fluoride in biological samples. Methods: Low levels of [18F]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [18F]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [18F]Fluoride was also determined in plasma and urine from mice injected with [18F]-labeled thymidine analogues using Method A. Results: The detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075±0.004 vs. 0.71±0.02 nCi). With Method A, [18F]fluoride was determined in plasma for [18F]FLT, [18F]FMAU, [18F]FEAU and N 3-[18F]FPrT as 1.4±0.31% (n=4), 0.17±0.49% (n=3), 4.88±1.62% (n=3) and 12.94±0.48% (n=4), respectively. The amount of [18F]fluoride determined in the urine was 11.49±1.60% (n=4) from [18F]FLT, 5.36±2.34% (n=3) from [18F]FMAU, 13.57±1.96% (n=3) from [18F]FEAU and 11.19±1.98% (n=4) from N 3-[18F]FPrT. Conclusion: Low levels of [18F]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C18 column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [18F]-labeled radiotracer and PET. [Copyright &y& Elsevier]

Introduction: Previous studies demonstrated that the lactose-binding protein (hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins (HIP/PAP)) is upregulated >130 times in peritumoral pancreatic tissue as compared to normal pancreatic tissue. Therefore, we developed a new radiolabeled ligand of HIP/PAP, the ethyl-β-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[¹⁸F]fluoro-β-D-glucopyranoside (Et-[¹⁸F]FDL) for noninvasive imaging of pancreatic carcinoma using positron emission tomography and computerized tomography (PET/CT).Methods: The novel precursor and radiolabeling methods for synthesis of Et-[¹⁸F]FDL produced no isomers; the average decay-corrected radiochemical yield was 68%, radiochemical purity >99%, and specific activity >74 GBq/µmol. The radioligand properties of Et-[¹⁸F]FDL were evaluated using an ex vivo autoradiography and immunohistochemistry in pancreatic tissue sections obtained from mice-bearing orthotopic pancreatic tumor xenografts.Results and Discussion: Et-[¹⁸F]FDL binding to peritumoral pancreatic tissue sections strongly correlated with HIP/PAP expression (r = 0.81) and could be completely blocked by treatment with 1 mM lactose.Conclusion: These results suggest that Et-[¹⁸F]FDL is a promising agent which should be evaluated for detection of early pancreatic carcinomas by PET/CT imaging. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: [18F]-Labeled analogues of thymidine have demonstrated efficacy for PET imaging of cellular proliferation. We have synthesized two [18F]-labeled N3-substituted thymidine analogues, N3-[18F]fluoroethyl thymidine (N3-[18F]-FET) and N3-[18F]fluoropropyl thymidine (N3-[18F]-FPrT), and performed preliminary PET imaging studies in tumor-bearing mice. Methods: Thymidine was converted to its 3′,5′-O-bis-tetrahydropyranyl ether, which was then converted to the N3-ethyl and propyl-substituted mesylate precursors. Reactions of these mesylate precursors with n-Bu4N[18F] or K[18F]/kryptofix followed by acid hydrolysis and HPLC purification yielded N3-[18F]-FET and N3-[18F]-FPrT, respectively. Subcutaneous (sc) xenografts of H441 human non–small cell lung cancer were established in two groups of mice (each n=6). Micro-PET images of the tumor-bearing animals were acquired after intravenous injection of N3-[18F]-FET or N3-[18F]-FPrT (3700 KBq/animal). Results: The radiochemical yields were 2–12% (d.c.) for N3-[18F]-FET and 30–38% (d.c.) for N3-[18F]-FPrT. Radiochemical purity was >99% and calculated specific activity was >74 GBq/μmol at the end of synthesis. The accumulation of N3-[18F]-FET and N3-[18F]-FPrT in the tumor tissue at 2 h postinjection was 1.81±0.78 and 2.95±1.14 percent injected dose per gram (%ID/g), respectively; tumor/muscle ratios were 5.57±0.82 and 7.69±2.18, respectively; the unidirectional influx rates (K i) were 0.013 and 0.018 ml/g per minute, respectively. Conclusion: Two novel [18F]- N3-substituted thymidine analogues have been synthesized in good yields, high purity and high specific activity. Preliminary in vivo studies demonstrated the efficacy of these [18F]- N3-substituted thymidine analogues for PET imaging of tumors. [Copyright &y& Elsevier]