Search

Cardiac blood pool imaging is currently performed almost exclusively with 99mTc-based compounds and SPECT/CT imaging. Using a generator-based PET radioisotope has a few advantages, including not needing nuclear reactors to produce it, obtaining better resolution in humans, and potentially reducing the radiation dose to the patient. When the shortlived radioisotope 68Ga is used, it can be applied repeatedly on the same day—for example, for the detection of bleeding. Our objective was to prepare and evaluate a long-circulating polymer functionalized with gallium for its biodistribution, toxicity, and dosimetric properties. A 500 kDa hyperbranched polyglycerol was conjugated to the chelator NOTA and radiolabeled rapidly at room temperature with 68Ga. It was then injected intravenously into a rat, and gated imaging allowed us to easily observe wall motion and cardiac contractility, confirming the suitability of this radiopharmaceutical for cardiac blood pool imaging. Internal radiation dose calculations showed that the radiation doses that patients would receive from the PET agent would be 2.5× lower than those from the 99mTc agent. A complete 14-day toxicology study in rats concluded that there were no gross pathology findings, changes in body or organ weights, or histopathological events. This radioactive-metal-functionalized polymer might be a suitable non-toxic agent to advance for clinical application. [ABSTRACT FROM AUTHOR]

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are 18F-labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20-40 %) at high specific activity (≥3 Ci/μmol) and at >98 % purity. PET imaging shows in vivo stability and tumor uptake. [ABSTRACT FROM AUTHOR]

Two carbonic anhydrase IX (CA IX) inhibitors were radiolabeled with 18F, and evaluated for imaging CA IX expression. Despite good affinity for CA IX and excellent plasma stability, uptake of both tracers in CA IX-expressing HT-29 tumor xenografts in mice was low. 18F-FEC accumulated predominately in the liver and nasal cavity, whereas a significant amount of 18F-U-104 was retained in blood. Due to minimal uptake in HT-29 tumors compared to other organs/tissues, these two tracers are not suitable for use for CA IX-targeted imaging. [ABSTRACT FROM AUTHOR]

Introduction: 2-[18F]Fluoroethoxy and 3-[18F]fluoropropoxy groups are common moieties in the structures of radiotracers used with positron emission tomography. The objectives of this study were (1) to develop an efficient one-step method for the preparation of 2-[18F]fluoroethanol (2-[18F]FEtOH) and 3-[18F]fluoropropanol (3-[18F]FPrOH); (2) to demonstrate the feasibility of using 2-[18F]FEtOH as a nucleophile for the synthesis of 2-[18F]fluoroethyl aryl esters and ethers; and (3) to determine the biodistribution profiles of 2-[18F]FEtOH and 3-[18F]FPrOH in mice. Methods: 2-[18F]FEtOH and 3-[18F]FPrOH were prepared by reacting n-Bu4N[18F]F with ethylene carbonate and 1,3-dioxan-2-one, respectively, in diethylene glycol at 165°C and purified by distillation. 2-[18F]fluoroethyl 4-fluorobenzoate and 1-(2-[18F]fluoroethoxy)-4-nitrobenzene were prepared by coupling 2-[18F]FEtOH with 4-fluorobenzoyl chloride and 1-fluoro-4-nitrobenzene, respectively. Biodistribution and PET/CT imaging studies of 2-[18F]FEtOH and 3-[18F]FPrOH were performed in normal female Balb/C mice. Results: The preparation of 2-[18F]FEtOH and 3-[18F]FPrOH took 60min, and their decay-corrected yields were 88.6±2.0% (n=9) and 65.6±10.2% (n=5), respectively. The decay-corrected yields for the preparation of 2-[18F]fluoroethyl 4-fluorobenzoate and 1-(2-[18F]fluoroethoxy)-4-nitrobenzene were 36.1±5.4% (n=3) and 27.7±10.7% (n=3), respectively. Imaging/biodistribution studies in mice using 2-[18F]FEtOH showed high initial radioactivity accumulation in all major organs followed by very slow clearance. On the contrary, by using 3-[18F]FPrOH, radioactivity accumulated in all major organs was cleared rapidly, but massive in vivo defluorination (31.3±9.57%ID/g in bone at 1h post-injection) was observed. Conclusions: Using 2-[18F]FEtOH/3-[18F]FPrOH as a nucleophile is a competitive new strategy for the synthesis of 2-[18F]fluoroethyl/3-[18F]fluoropropyl aryl esters and ethers. Our biodistribution data emphasize the importance of in vivo stability of PET tracers containing a 2-[18F]fluoroethyl or 3-[18F]fluoropropyl group due to high background and high bone uptake resulting from 2-[18F]FEtOH and 3-[18F]FPrOH, respectively. This is especially important for their aryl ester derivatives which are prone to in vivo hydrolysis. [ABSTRACT FROM AUTHOR]

Introduction: Prostate incidentalomas are prostatic lesions suspicious for cancer discovered by imaging patients without a known history of prostatic cancer (PCa) for other reasons. 18-fluoro-2- deoxy-D-glucose positron emission tomography/computed tomography (FDG PET) is used to diagnose, stage, and assess response to treatment for numerous cancers, but it is not routinely used for PCa. We aimed to determine the rate of detection of prostate incidentalomas in patients undergoing FDG PET and to evaluate the natural history of these lesions. Methods: A retrospective review was conducted of all FDG PET scans performed between 2005 and 2017 at a single institution. Patients were selected who had prostatic uptake without a history of PCa. Clinical data were collected from electronic medical records to determine how the prostate incidentalomas were further evaluated and to define the rate of malignancy. Results: A prostate incidentaloma was identified in 309 (1.0%) of 31 019 FDG PET scans performed on men. A prostate-specific antigen (PSA) test was obtained in 40.1% of patients within six months of prostate incidentaloma detection. Six patients underwent a multiparametric magnetic resonance imaging (mpMRI) of the prostate, which identified PCa in one case. Overall, PCa was diagnosed in 33 cases, representing 10.7% of the prostate incidentalomas and 0.1% of the scanned patients. PCa was intermediate- or high-risk in 27 (8.7%) of the prostate incidentalomas. Conclusions: Incidental lesions detected in the prostate by FDG PET may represent clinically significant PCa. Referral to a urologist for further evaluation should be considered if the patient is otherwise in reasonable health. [ABSTRACT FROM AUTHOR]

Die Zeit drängt. Die geringe Reaktivität wässriger Fluoridionen war lange ein Problem bei der Markierung mit 18F. In der Zuschrift auf S. 12070 ff. stellen D. M. Perrin et al. Trifluoroborat ‐ Peptid ‐ Konjugate vor, die in Wasser innerhalb von 15 Minuten durch Isotopenaustausch in 18F ‐ Marker mit hoher spezifischer Aktivität überführt werden. Auf zeitaufwändige HPLC kann dabei verzichtet werden. Mehrere bioaktive Liganden ermöglichen die PET ‐ Bildgebung von In ‐ vivo ‐ Zielen. [ABSTRACT FROM AUTHOR]

Time is the essence for 18F labeling. The poor reactivity of aqueous fluoride ions has long been a challenge in 18F labeling. In their Communication on page 11876 ff., D. M. Perrin et al. present trifluoroborate–peptide conjugates that are labeled by isotopic exchange in water within 15 minutes to provide 18F tracers with high specific activity. Time‐consuming HPLC can be avoided. Several bioactive ligands enable PET imaging of in vivo targets. [ABSTRACT FROM AUTHOR]

The bradykinin receptor B1R is overexpressed in many human cancers where it might be used as a general target for cancer imaging. In this study, we evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. Three synthetic derivatives were evaluated in vitro and in vivo for receptor binding and their ability to visualize tumors by PET. Enalaprilat and phosphoramidon were used to evaluate the impact of peptidases on tumor visualization. While we found that radiolabeled peptides based on the native kallidin sequence were ineffective at visualizing B1R-positive tumors, peptidase inhibition with phosphoramidon greatly enhanced B1R visualization in vivo. Two stabilized derivatives incorporating unnatural amino acids (68Ga-SH01078 and 68Ga-P03034) maintained receptor-binding affinities that were effective, allowing excellent tumor visualization, minimal accumulation in normal tissues, and rapid renal clearance. Tumor uptake was blocked in the presence of excess competitor, confirming that the specificity of tumor accumulation was receptor mediated. Our results offer a preclinical proof of concept for noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers. [ABSTRACT FROM AUTHOR]

Abstract: Acetylene-bearing 2-[18F]fluoropyridines [18F]FPy5yne and PEG-[18F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [18F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6–14) analogues via copper-catalyzed azide–alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing 18F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated 18F peptide. Assessment of water-soluble peptide pharmacokinetics and tumour-targeting capabilities in a mouse model of prostate cancer is currently underway. [Copyright &y& Elsevier]

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are (18)F-labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20-40%) at high specific activity (≥3 Ci/μmol) and at >98% purity. PET imaging shows in vivo stability and tumor uptake., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two carbonic anhydrase IX (CA IX) inhibitors were radiolabeled with (18)F, and evaluated for imaging CA IX expression. Despite good affinity for CA IX and excellent plasma stability, uptake of both tracers in CA IX-expressing HT-29 tumor xenografts in mice was low. (18)F-FEC accumulated predominately in the liver and nasal cavity, whereas a significant amount of (18)F-U-104 was retained in blood. Due to minimal uptake in HT-29 tumors compared to other organs/tissues, these two tracers are not suitable for use for CA IX-targeted imaging.

A clickable alkyne-modified arylborimidine is rapidly converted in 15 minutes to a highly polar (18)F-aryltrifluoroborate anion ((18)F-ArBF(3) (-)) at high specific activity. Following labeling, the alkyne-(18)F-ArBF(3) (-) was conjugated to the peptide bombesin (BBN) within 25 minutes in a second step without need for prior work-up making this one-pot-two-step method easy, user-friendly, and generally applicable. Bombesin was chosen to provide functional PET images of prostate cancer xenografts in mice of which there are few. Whereas BBN is labeled to provide some of the first in vivo tumor images based on this technique, click-labeling is recognized for its generality and broad substrate scope. Hence these results are likely to be useful for click labeling most peptides and other biomolecules.