:The most common semiquantitative method of evaluation of pulmonary lesions using 18 F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules. Methods:Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUV max for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUV max cutoff of 2.5. Results:The linear regression equations and (R 2 )s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm) are plotted in a dot diagram using an SUV max cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUV max cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1-2.0 cm); 94%, 23%, and 76%, respectively for group 3 (2.1-3.0 cm); and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUV max cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules. Conclusion:The slope of the regression line is greater for malignant than for benign nodules. Although, the SUV max cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of small pulmonary nodules (≤ 1.0 cm).

Abnormal tryptophan metabolism catalyzed by indoleamine 2,3-dioxygenase may play a prominent role in tumor immunoresistance in many tumor types, including lung tumors. The goal of this study was to evaluate the in vivo kinetics of a-11 C-methyl-L-tryptophan (AMT), a PET tracer for tryptophan metabolism, in human lung tumors. Methods: Tracer transport and metabolic rates were evaluated in 18 lesions of 10 patients using dynamic PET/CT with AMT. The kinetic values were compared between tumors and unaffected lung tissue, tested against a simplified analytic approach requiring no arterial blood sampling, and correlated with standardized uptake values (SUVs) obtained from 18 F-FDG PET/CT scans. Results: Most non-small cell lung cancers (NSCLCs) showed prolonged retention of AMT, but 3 other lesions (2 benign lesions and a rectal cancer metastasis) and unaffected lung tissue showed no such retention. Transport and metabolic rates of AMT were substantially higher in NSCLCs than in the other tumors and unaffected lung tissue. A simplified analytic approach provided an excellent estimate of transport rates but only suboptimal approximation of tryptophan metabolic rates. 18 F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates. Conclusion: Prolonged retention of AMT in NSCLCs suggests high metabolic rates of tryptophan in these tumors. AMT PET/CT may be a clinically useful molecular imaging method for personalized cancer treatment by identifying and monitoring patients who have increased tumor tryptophan metabolism and are potentially sensitive to immunopharmacotherapy with indoleamine 2,3-dioxygenase inhibitors. Trypt ophan is an essential amino acid required for biosynthesis of proteins, serotonin, and melatonin in the brain and other tissues (1). In mammals, however, most of the tryptophan derived from the diet is metabolized via the kynurenine pathway (2). Abnormal tryptophan oxidation along this pathway is an important mechanism for modulation of tumor cell proliferation and immunoresistance, mainly via the initial and rate-limiting step catalyzed by indoleamine 2,3-dioxygenase (IDO) (3,4). Induction of IDO leads to local tryptophan depletion, thus inhibiting cell growth in some malignant tumors (5,6). On the other hand, enhanced IDO activity in tumors may also exert a potent immunosuppressive effect by blocking T-lymphocyte proliferation, thus diminishing T-cell-mediated tumor rejection (3,4,7). Thus, manipulation of tryptophan metabolism via the kynurenine pathway may have important implications in tumor pharmacotherapy. However, it is not always clear whether IDO activity should be enhanced or inhibited to suppress tumor growth in specific tumors.Recent studies have consistently shown high expression of IDO in a variety of human tumors, including lung tumors (3,(8)(9)(10)(11)(12)(13)(14). Several of these studies demonstrated that high expression of IDO was associated with reduced survival (9)(10)(11)14). In vivo de...

Partial deprotonation of the bicyclic guanidine 1,4,6-triazabicyclo[3.3.0]oct-4-ene (Htbo) is achieved using (n)BuLi. Isolation of the resulting lithium salts has resulted in the structural characterization of the mixed anion complex {[Li(tbo)(VIII)(tboH)](2)}(infinity) (where -H = 1-(2-aminoethyl)-2-imidazolidinethione) and the partially deprotonated salt Li(6)(tbo)(6)(Htbo)(3), 1b. The neutral guanidine Htbo reacts cleanly with AlMe(3) and ZnMe(2) to afford the organometallic complexes [Al(tbo)Me(2)](2) [2](2), and Zn(3)(tbo)(4)Me(2) (3). Structural characterization of these compounds enables comparison between the {5:5}-bicyclic system, [tbo](-), and the previously reported {6:6}-bicyclic system, [hpp](-) (where hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine). Results indicate that delocalization within the [tbo](-) anion is restricted to the CN(2) amidinate component, with retention of electron density in the non-bonding nitrogen lone-pair. These conclusions are supported by a DFT analysis of the neutral guanidines, Htbo and hppH.

Protonation of the {6,6}-and {5,5}-bicyclic guanidines 1, 3,4,6,7,8-hexahydro-2H-pyrimido [1,2-a] pyrimidine (hppH) and 1,4,6-triazabicyclo[3.3.0]oct-4-ene (Htbo), respectively, to afford the hydrochloride salts [hppH 2 ][Cl] (1a) and [HtboH][Cl] (2) was achieved using [NEt 3 H][Cl]. Anion exchange involving 1a and NaBPh 4 generated the borate salt [hppH 2 ][BPh 4 ] (1c). Crystal structure analysis of 1a and the analogous hydrobromide salt [hppH 2 ][Br] (1b) showed two NH/X hydrogenbonds between the cation and the anion, and association of the [hppH 2 ][X] ion-pairs into dimeric units.In salt 1c the [hppH 2 ] + cation was shown to be located within a cavity defined by phenyl substituents from the [BPh 4 ] À anion, with no hydrogen bonding present. Reducing the size of the heterocyclic rings from {6,6}-to {5,5}-in the [HtboH] + salt promotes formation of extended structures due to a wider angle between the projected hydrogen-bonds to the halide anion. Results from analysis of the bond parameters within the guanidinium cations are used to explain the distribution of p-electron density throughout the bicyclic framework.