A technique to quantify very low activities in regions of interest with a collimatorless detector.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111 Bq (3 nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy.

AIM: To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. MATERIALS AND METHODS: The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. RESULTS: Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). CONCLUSIONS: In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.

Dicarboxylic acids as pH sensors for hyperpolarized 13C magnetic resonance spectroscopic imaging.

Imaging tumoral pH may help to characterize aggressiveness, metastasis, and therapeutic response. We report the development of hyperpolarized [2-13C,D10]diethylmalonic acid, which exhibits a large pH-dependent 13C chemical shift over the physiological range. We demonstrate that co-polarization with [1-13C,D9]tert-butanol accurately measures pH via13C NMR and magnetic resonance spectroscopic imaging in phantoms.

[(11)C]Ascorbic and [(11)C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography.

Here we report the radiosynthesis of an endogenous redox pair, [(11)C]ascorbic acid ([(11)C]VitC) and [(11)C]dehydroascorbic acid ([(11)C]DHA), the reduced and oxidized forms of vitamin C, and their application to ROS sensing. These results provide the basis for in vivo detection of ROS using positron emission tomography (PET).

Dynamic nuclear polarization of biocompatible (13)C-enriched carbonates for in vivo pH imaging.

A hyperpolarization technique using carbonate precursors of biocompatible molecules was found to yield high concentrations of hyperpolarized (13)C bicarbonate in solution. This approach enabled large signal gains for low-toxicity hyperpolarized (13)C pH imaging in a phantom and in vivo in a murine model of prostate cancer.

Synthesis and beta-lactamase reactivity of alpha-substituted phenaceturates.

Beta-lactams with 6alpha (penicillins) or 7alpha (cephalosporins) substituents are often beta-lactamase inhibitors. This paper assesses the effect of such substituents on acyclic beta-lactamase substrates. Thus, a series of m-carboxyphenyl phenaceturates, substituted at the glycyl alpha-carbon by -OMe, -CH(2)OH, -CO(2)(-), and -CH(2)NH(3)(+), have been prepared, and tested for their reactivity against serine beta-lactamases. The latter two are novel substituents in beta-lactamase substrates. The methoxy and hydroxymethyl compounds were found to be poor to moderately good substrates, depending on the enzyme. The aminomethyl compound gave rise to a transiently stable (t(1/2)=4.6s) complex on its reaction with a class C beta-lactamase. The reactivity of the compounds against three low molecular weight DD-peptidases was also tested. Again, the methoxy and hydroxymethyl compounds proved to be quite good substrates with no sign of inhibitory complexes. The DD-peptidases reacted with one enantiomer (the compounds were prepared as racemates), presumably the D compound. The class C beta-lactamase reacted with both D and L enantiomers although it preferred the latter. The structural bases of these stereo-preferences were explored by reference to the crystal structure of the enzyme by molecular modeling studies. The aminomethyl compound was unreactive with the DD-peptidases, whereas the carboxy compound did not react with any of the above-mentioned enzymes. The inhibitory effects of the -OMe and -CH(2)OH substituents in beta-lactams apparently require a combination of the substituent and the pendant leaving group of the beta-lactam at the acyl-enzyme stage.