Preclinical PET Imaging and Toxicity Study of a Ga-Functionalized Polymeric Cardiac Blood Pool Agent.

Cardiac blood pool imaging is currently performed almost exclusively with Tc-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 Ga is used, it can be applied repeatedly on the same day-for example, for the detection of bleeding.

The Value of PET-CT in Ovarian Epithelial Carcinoma: A Population-Based Study in British Columbia, Canada.

Introduction: In epithelial ovarian cancer (EOC), consensus regarding optimal use of PET/CT is lacking. Limited evidence suggests its accuracy in preoperative staging, investigating recurrence and predicting optimal secondary debulking. This study evaluated indications for PET/CT, impact of PET/CT results on EOC management, and its added value over conventional imaging.

Incidentalomas of the prostate detected by 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography.

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.

One-step (18)F labeling of biomolecules using organotrifluoroborates.

Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous (18)F fluoride ((18)F(-)) and used for positron emission tomography (PET) imaging. Among the β(+)-emitting radionuclides, fluorine-18 ((18)F) is the isotope of choice for PET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be (18)F-labeled in one step in aqueous conditions via (18)F-(19)F isotope exchange.

(18)F-AmBF3-MJ9: a novel radiofluorinated bombesin derivative for prostate cancer imaging.

A novel radiofluorinated derivative of bombesin, (18)F-AmBF3-MJ9, was synthesized and evaluated for its potential to image prostate cancer by targeting the gastrin releasing peptide receptor (GRPR). AmBF3-MJ9 was prepared from an ammoniomethyl-trifluoroborate (AmBF3) conjugated alkyne 2 and azidoacetyl-MJ9 via a copper-catalyzed click reaction, and had good binding affinity for GRPR (Ki=0.5±0.

In vivo radioimaging of bradykinin receptor b1, a widely overexpressed molecule in human cancer.

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.

An organotrifluoroborate for broadly applicable one-step 18F-labeling.

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.

Preclinical evaluation of a high-affinity 18F-trifluoroborate octreotate derivative for somatostatin receptor imaging.

Unlabelled: Recent studies have highlighted the high sensitivity of PET imaging with (68)Ga-labeled octreotide derivatives for the detection and staging of neuroendocrine tumors. A somatostatin receptor ligand that is easily radiolabeled with (18)F-fluoride could improve the availability of PET imaging of neuroendocrine tumors. We report an alkyltrifluoroborate-octreotate conjugate that is radiolabeled in a 1-step (18)F exchange reaction in high yield and with high specific activity.

f-[18F]fluoroethanol and 3-[18F]fluoropropanol: facile preparation, biodistribution in mice, and their application as nucleophiles in the synthesis of [18F]fluoroalkyl aryl ester and ether PET tracers.

Introduction: 2-[(18)F]Fluoroethoxy and 3-[(18)F]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-[(18)F]fluoroethanol (2-[(18)F]FEtOH) and 3-[(18)F]fluoropropanol (3-[(18)F]FPrOH); (2) to demonstrate the feasibility of using 2-[(18)F]FEtOH as a nucleophile for the synthesis of 2-[(18)F]fluoroethyl aryl esters and ethers; and (3) to determine the biodistribution profiles of 2-[(18)F]FEtOH and 3-[(18)F]FPrOH in mice.

Methods: 2-[(18)F]FEtOH and 3-[(18)F]FPrOH were prepared by reacting n-Bu4N[(18)F]F with ethylene carbonate and 1,3-dioxan-2-one, respectively, in diethylene glycol at 165°C and purified by distillation.

2-Fluoropyridine prosthetic compounds for the 18F labeling of bombesin analogues.

Acetylene-bearing 2-[(18)F]fluoropyridines [(18)F]FPy5yne and PEG-[(18)F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [(18)F]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 (18)F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated (18)F peptide.

Synthesis and evaluation of 18F-labeled carbonic anhydrase IX inhibitors for imaging with positron emission tomography.

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.

(18)F-click labeling of a bombesin antagonist with an alkyne-(18)F-ArBF(3) (-): in vivo PET imaging of tumors expressing the GRP-receptor.

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.

Proximal fluid proteome profiling of mouse colon tumors reveals biomarkers for early diagnosis of human colorectal cancer.

Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC.

Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins.