Somatostatin Receptor Imaging with [F]FET-βAG-TOCA PET/CT and [Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study.

There is a clinical need for F-labeled somatostatin analogs for the imaging of neuroendocrine tumors (NET), given the limitations of using [Ga]Ga-DOTA-peptides, particularly with regard to widespread accessibility. We have shown that [F]fluoroethyl-triazole-[Tyr]-octreotate ([F]FET-βAG-TOCA) has favorable dosimetry and biodistribution. As a step toward clinical implementation, we conducted a prospective, noninferiority study of [F]FET-βAG-TOCA PET/CT compared with [Ga]Ga-DOTA- peptide PET/CT in patients with NET.

Bench to Bedside Development of [F]Fluoromethyl-(1,2-H)choline ([F]D4-FCH).

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [F]fluoromethyl-[1,2-H]choline ([F]D4-FCH). [F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a H/D isotope effect, together with fluorine substitution.

Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [F]fluoromethyl-(1,2-H)-choline.

: The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited.

Clinical translation of F-fluoropivalate - a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers.

Background: Fatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including C-acetate, and F-FAC (2-F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed F-fluoropivalate (F-FPIA; 3-F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism.

Exploiting altered patterns of choline kinase-alpha expression on human prostate tissue to prognosticate prostate cancer.

Aims: Malignant transformation results in overexpression of choline-kinase (CHK) and altered choline metabolism, which is potentially detectable by immunohistochemistry (IHC). We investigated the utility of CHK-alpha (CHKA) IHC as a complement to current diagnostic investigation of prostate cancer by analysing expression patterns in normal (no evidence of malignancy) and malignant human prostate tissue samples.

Methods: As an initial validation, paraffin-embedded prostatectomy specimen blocks with both normal and malignant prostate tissue were analysed for CHKA protein and mRNA expression by western blot and quantitative reverse transcriptase PCR (qRT-PCR), respectively.

Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer.

Background: Brain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access.

Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers.

Unlabelled: (11)C-choline and (18)F-fluoromethylcholine ((18)F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, (18)F-fluoromethyl-[1,2-(2)H4]choline ((18)F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-D4-FCH in 8 healthy human volunteers.

18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry.

Unlabelled: Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, (18)F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), has been developed for use in PET studies.

Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy.

We studied the relation between adherence to imatinib measured with microelectronic monitoring systems and the probabilities of losing a complete cytogenetic response (CCyR) and of imatinib failure in 87 CCyR chronic myeloid leukemia patients receiving long-term therapy. We included in our analysis the most relevant prognostic factors described to date. On multivariate analysis, the adherence rate and having failed to achieve a major molecular response were the only independent predictors for loss of CCyR and discontinuation of imatinib therapy.

Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib.

Purpose: There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence.

Methods: Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.