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Arginine-glycine-aspartic acid (RGD)-containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for α5 β1 integrin receptor have been developed with promising results. Sixty-one antagonists were screened, and tert-butyl (S)-3-(2-((3R,5S)-1-(3-(1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)propanoyl)-5-((pyridin-2-ylamino)methyl)pyrrolidin-3-yloxy)acetamido)-2-(2,4,6-trimethylbenzamido)propanoate (FPMt) was selected for the development of a PET tracer to image the expression of α5 β1 integrin receptors. An alkynyl precursor (PMt) was initially synthesized in six steps, and its radiolabeling was performed according to the azide-alkyne copper(II)-catalyzed Huisgen's cycloaddition by using 1-azido-2-[(18)F]fluoroethane ([(18)F]12). Different reaction conditions between PMt and [(18)F]12 were investigated, but all of them afforded [(18)F]FPMt in 15 min with similar radiochemical yields (80-83%, decay corrected). Overall, the final radiopharmaceutical ([(18)F]FPMt) was obtained after a synthesis time of 60-70 min in 42-44% decay-corrected radiochemical yield.

ω-Conotoxin GVIA is a potent, irreversible antagonist of N-type voltage gated Ca2+ channels. A radiofluorinated analogue of GVIA could be useful in assessing regional synaptic density of the brain, in vivo, using positron emission tomography. N-hydroxy succinimidyl 4-[18F]fluorobenzoate was employed to site-specifically label GVIA, preserving native binding affinity. The tracer was characterized with MALDI-TOF mass spectrometry and colorimetric protein assay. Radiochemical decay-corrected yield of the lysine-24 labeled analogue of [18F]GVIA was 5%. Specific activity of this species was determined to be 1.2 × 105 Ci/mmol. Encapsulation of the tracer in sulfatide containing liposomes, a potential method for enhancing blood–brain penetrance, was accomplished with 40% efficiency. Copyright © 2006 John Wiley & Sons, Ltd.

Inhibitors of tyrosine kinase enzymatic activity represent a promising new class of antineoplastic agents. Although clinical studies performed over the last decade give more insight on the potential therapeutic applications of such drugs, identification of the individual patients who might benefit from them remains a major challenge. We have developed a synthetic strategy for the production of a wide variety of radiolabeled 6,7-disubstituted 4-anilinoquinazolines suitable for noninvasive imaging of tyrosine kinase receptors to predict therapy effectiveness. Three new F-18 labeled radiopharmaceuticals based on the therapeutic agents Tarceva, Iressa, and ZD6474 were synthesized. Decay-corrected yields varied between 25 and 40% for a total synthesis time of 120 min, thus providing F-18 labeled tyrosine kinase inhibitors in quantities and times practical for use as PET radiopharmaceuticals. Copyright © 2005 John Wiley & Sons, Ltd.

Anthracyclines are among the most widely used antineoplastic agents in current clinical practice. Nevertheless, chemoresistance, which results in failure to eradicate the tumor, is often observed after administration of anthracyclines, and no assay system has yet been found to accurately predict tumor resistance to those antitumor agents. We sought to prepare an F-18 labeled derivative of idarubicin, a 4-demethoxy-daunorubicin analogue, to use in helping to assess physiologic resistance to anthracyclines in vivo. Two different synthetic pathways, which required the preparation of the key intermediate [18F]fluorobenzoic acid ([18F]FBA), are advanced to label idarubicin with F-18 on its primary amine. The first approach yielded the desired [18F]fluorobenzoate idarubicin derivative in two steps from [18F]FBA, while the second strategy consisted of a direct acylation of idarubicin by treatment with [18F]FBA in presence of diethyl cyanophosphonate. Although the first method led to fewer byproducts, it required more time to obtain the HPLC-purified radiopharmaceutical (100 min vs 90 min) and resulted in lower radiochemical yields (8–25% vs 25–39% decay corrected from starting fluoride). Copyright © 2005 John Wiley & Sons, Ltd.

We have prepared the 2- and 4-fluoro derivatives of 16α-[18F]fluoroestradiol (FES) (4a, b) and 11β-OMe-FES (4c, d). Electrophilic substitution of estrone or 11β-OMe-estrone with N-fluoropyridinium salt gave the 2-and 4-F derivatives 1, which were converted to the triols 2 and subsequently to the reactive 16β, 17β-cyclic sulfates 3. Stereoselective opening of the cyclic sulfates via nucleophilic fluorination with Me4NF or [18F]F- and removal of the protecting ether and sulfate groups via rapid acid hydrolysis gave 4a-d or [16α-18F]-(4a-d).