Despite technical advances in many areas of diagnostic radiology, the detection and imaging of human cancer remains poor. A meaningful impact on cancer screening, staging, and treatment is unlikely to occur until the tumor-to-background ratio improves by three to four orders of magnitude (ie, 10(3)- to 10(4)-fold), which in turn will require proportional improvements in sensitivity and contrast agent targeting. This review analyzes the physics and chemistry of cancer imaging and highlights the fundamental principles underlying the detection of malignant cells within a background of normal cells. The use of various contrast agents and radiotracers for cancer imaging is reviewed, as are the current limitations of ultrasound, x-ray imaging, magnetic resonance imaging (MRI), single-photon emission computed tomography, positron emission tomography (PET), and optical imaging. Innovative technologies are emerging that hold great promise for patients, such as positron emission mammography of the breast and spectroscopy-enhanced colonoscopy for cancer screening, hyperpolarization MRI and time-of-flight PET for staging, and ion beam-induced PET scanning and near-infrared fluorescence-guided surgery for cancer treatment. This review explores these emerging technologies and considers their potential impact on clinical care. Finally, those cancers that are currently difficult to image and quantify, such as ovarian cancer and acute leukemia, are discussed.

/pdf/new-technologies-for-human-cancer-imaging-3hvdicnoms.pdf

New Technologies for Human Cancer Imaging

Mobile single-sided NMR

Since 1999 several groups have analyzed nutritional supplements with mass spectrometric methods (GC/MS, LC/MS/MS) for contaminations and adulterations with doping substances. These investigations showed that nutritional supplements contained prohibited stimulants as ephedrines, caffeine, methylenedioxymetamphetamie and sibutramine, which were not declared on the labels. An international study performed in 2001 and 2002 on 634 nutritional supplements that were purchased in 13 different countries showed that about 15% of the nonhormonal nutritional supplements were contaminated with anabolic-androgenic steroids (mainly prohormones). Since 2002, also products intentionally faked with high amounts of 'classic' anabolic steroids such as metandienone, stanozolol, boldenone, dehydrochloromethyl-testosterone, oxandrolone etc. have been detected on the nutritional supplement market. These anabolic steroids were not declared on the labels either. The sources of these anabolic steroids are probably Chinese pharmaceutical companies, which sell bulk material of anabolic steroids. In 2005 vitamin C, multivitamin and magnesium tablets were confiscated, which contained cross-contaminations of stanozolol and metandienone. Since 2002 new 'designer' steroids such as prostanozol, methasterone, androstatrienedione etc. have been offered on the nutritional supplement market. In the near future also cross-contaminations with these steroids are expected. Recently a nutritional supplement for weight loss was found to contain the beta2-agonist clenbuterol. The application of such nutritional supplements is connected with a high risk of inadvertent doping cases and a health risk. For the detection of new 'designer' steroids in nutritional supplements, mass spectrometric strategies (GC/MS, LC/MS/MS) are presented.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jms.1452

Nutritional supplements cross-contaminated and faked with doping substances

The theory and practice of hyperpolarization in magnetic resonance using parahydrogen

Magnetic resonance (MR) is one of the most versatile and useful physical effects used for human imaging, chemical analysis, and the elucidation of molecular structures. However, its full potential is rarely used, because only a small fraction of the nuclear spin ensemble is polarized, that is, aligned with the applied static magnetic field. Hyperpolarization methods seek other means to increase the polarization and thus the MR signal. A unique source of pure spin order is the entangled singlet spin state of dihydrogen, parahydrogen (pH2 ), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows the MR signal to be enhanced by several orders of magnitude. Considerable progress has been made in the past decade in the area of pH2 -based hyperpolarization techniques for biomedical applications. It is the goal of this Review to provide a selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, preparation of the contrast agents, and applications.

Parahydrogen-Based Hyperpolarization for Biomedicine

The discovery of the designer steroid tetrahydrogestrinone (THG) in elite athletes' doping control samples in 2003 demonstrated the availability of steroid derivatives prepared solely for doping purposes. Modern mass spectrometers utilizing electrospray ionization and collisionally activated dissociation (CAD) of analytes allow the structural characterization of steroids and their derivatization sites by the elucidation of fragmentation behaviors. A total of 21 steroids comprising either a 4,9,11-triene, a 3-keto-4-ene or a 3-keto-1-ene nucleus were investigated regarding their dissociation pathways, deuterated analogues were synthesized and fragmentation routes were postulated, permitting the identification of steroidal structures and modifications. Compounds based on a 4,9,11-triene steroid with an ethyl residue at C-13 (gestrinone analogues) generate abundant fragment ions at m/z 241 and 199, whereas the substitution of the C-13 ethyl group by a methyl residue (trenbolone analogues) results in a shift of m/z 241 to 227. Substances related to testosterone with a 3-keto-4-ene structure give rise to abundant fragment ions at m/z 109 and 97 whereas steroids with a 3-keto-1-ene nucleus eliminate the A-ring including the carbons C-1–C-4, in addition to C-19 that is proposed to migrate from C-10 to C-1 under CAD conditions. Copyright © 2005 John Wiley & Sons, Ltd.

Characterization of chemically modified steroids for doping control purposes by electrospray ionization tandem mass spectrometry

Recently, Levitt and co-workers demonstrated that conserving the population of long-lasting nuclear singlet states in weak magnetic fields can lead to a preservation of nuclear spin information over times substantially longer than governed by the (high-field) spin-lattice relaxation time T1. Potential benefits of the prolonged spin information for magnetic resonance imaging and spectroscopy were pointed out, particularly when combined with the parahydrogen induced polarization (PHIP) methodology. In this contribution, we demonstrate that an increase of the effective relaxation time by a factor up to three is achieved experimentally, when molecules hyperpolarized by PHIP are kept in a weak magnetic field instead of the strong field of a typical NMR magnet. This increased lifetime of spin information makes the known PHIP phenomena more compatible with the time scales of biological processes and, thus, more attractive for future investigations.

/pdf/generating-long-lasting-1h-and-13c-hyperpolarization-in-3cuupkbmc3.pdf

Generating Long-Lasting 1H and 13C Hyperpolarization in Small Molecules with Parahydrogen-Induced Polarization

Homogeneous hydrogenations of unsaturated substrates with parahydrogen yield strong NMR signal enhancements of the transferred 1H nuclei if the symmetry of H2 is broken in the resulting hydrogenated products. This chemically induced hyperpolarization known as Parahydrogen-induced polarization (PHIP) is also transferred to other protons and heteronuclei (2H, 13C, 29Si, 31P) when the hydrogenation is initiated at low magnetic fields. Hydrogenating various fluorinated styrenes and phenylacetylenes, we show that PHIP-derived hyperpolarization is transferred to 19F not only in the Earth's magnetic field (ALTADENA condition) but also in a strong magnetic field, e.g., when carrying out the reaction in the NMR spectrometer (PASADENA condition). Upon conducting a systematic analysis of the observed PHIP transfer to 1H, 13C, and 19F in the hydrogenation products to elucidate the mechanisms that govern this parahydrogen-aided resonance transfer (PART), we conclude that high- and low-field PHIP transfer mechanisms differ in detail depending on either through-bond or through-space interactions. Substrates with high hydrogenation rates and long spin-lattice relaxation times (T1) yield the highest degree of heteronuclear hyperpolarization. Possible medical applications for hyperpolarized 19F-containing molecules as "active" contrast agents for magnetic resonance imaging (MRI) are outlined.

Transfer of parahydrogen-induced hyperpolarization to 19F.

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Characterization of chemically modified steroids for doping control purposes by electrospray ionization tandem mass spectrometry

Generating Long-Lasting 1H and 13C Hyperpolarization in Small Molecules with Parahydrogen-Induced Polarization

Transfer of parahydrogen-induced hyperpolarization to 19F.