Positron Emission Tomography Imaging of CD105 Expression with a 64Cu-Labeled Monoclonal Antibody: NOTA Is Superior to DOTA

Optimizing the in vivo stability of positron emission tomography (PET) tracers is of critical importance to cancer diagnosis. In the case of 64Cu-labeled monoclonal antibodies (mAb), in vivo behavior and biodistribution is critically dependent on the performance of the bifunctional chelator used to conjugate the mAb to the radiolabel. This study compared the in vivo characteristics of 64Cu-labeled TRC105 (a chimeric mAb that binds to both human and murine CD105), through two commonly used chelators: 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Flow cytometry analysis confirmed that chelator conjugation of TRC105 did not affect its CD105 binding affinity or specificity. PET imaging and biodistribution studies in 4T1 murine breast tumor-bearing mice revealed that 64Cu-NOTA-TRC105 exhibited better stability than 64Cu-DOTA-TRC105 in vivo, which resulted in significantly lower liver uptake without compromising the tumor targeting efficiency. In conclusion, this study confirmed that NOTA is a superior chelator to DOTA for PET imaging with 64Cu-labeled TRC105

Location coordinates of rodents and ectoparasites collection sites in Thailand (2012–2013).

<p>Surveillance activities were conducted in 4 regions and 8 provinces in Thailand. The Northern region (Chiangrai and Phayao provinces), the Northeastern region (Loei and Nong Bua Lam Phu provinces), and the Southern region (Chumphon and Surat Thani provinces).</p><p>Location coordinates of rodents and ectoparasites collection sites in Thailand (2012–2013).</p

Distribution of <i>Bartonella</i> DNA among rodent species in different regions and provinces of Thailand, 2012–2013.

<p>^a<i>Bartonella</i> DNA was detected by <i>ssr</i>A and <i>nuo</i>G genes. The positivity for each sample was recorded only when 2 assays produced the concordant results.</p><p>Distribution of <i>Bartonella</i> DNA among rodent species in different regions and provinces of Thailand, 2012–2013.</p

<i>Bartonella</i> species identified in rodents and their associated ectoparasites based on <i>glt</i>A gene sequence similarities

<p>^a<i>L</i>. <i>deliense</i>.</p><p>^b Mite species was not available since there were only 3 mites collected from this host and no slide was made for species identification.</p><p>^<b>c</b><i>Bartonella</i> DNA was equally detected in <i>Polyplax</i> and <i>Hoplopleura</i> lice.</p><p>^d<i>Polyplax</i> spp.</p><p><i>Bartonella</i> species identified in rodents and their associated ectoparasites based on <i>glt</i>A gene sequence similarities</p

Percent similarity of <i>glt</i>A sequence for <i>Bartonella</i> identification detected from rodents (R) and their associated ectoparasites; Mite (M), flea (F), tick (T), and louse (L).

<p>^a Group 1 consists of sample no. R1023, R1025, R1026, R1028, R1181, R1195, R1197, L1028, M1200, L1206, L1354, and L1355.</p><p>^b Group 2 consists of sample no. R1012, R1033, F1413, F1437, F2386, F2495, and F2532.</p><p>^c Group 3 consists of sample no. T1005, L1025, M1189, L1194, L1227, and L1596.</p><p>^d Group 4 consists of sample no. R1072, R1073, R1136, R1144, R1168, L1080, T1513, and T1521.</p><p>Percent similarity of <i>glt</i>A sequence for <i>Bartonella</i> identification detected from rodents (R) and their associated ectoparasites; Mite (M), flea (F), tick (T), and louse (L).</p

Comparison <i>of Bartonella</i> prevalence in ectoparasites collected from <i>Bartonella</i>-positive and <i>Bartonella</i>-negative rodents.

<p>^a There are 2 samples where <i>Bartonella</i> was detected in host (<i>R</i>. <i>rattus</i>), mite, and lice; 1–4 pools of ticks and fleas can be collected from one rodent.</p><p>^b<i>Bartonella</i> DNA prevalence in ectoparasites collected from positive rats (19.4%) were higher significantly (Chi-Square Tests, <i>P</i> = 0.003) comparing to ectoparasites from negative rats (8.7%).</p><p>Comparison <i>of Bartonella</i> prevalence in ectoparasites collected from <i>Bartonella</i>-positive and <i>Bartonella</i>-negative rodents.</p

The Distribution and Diversity of <i>Bartonella</i> Species in Rodents and Their Ectoparasites across Thailand

<div><p>Our study highlights the surveillance of <i>Bartonella</i> species among rodents and their associated ectoparasites (ticks, fleas, lice, and mites) in several regions across Thailand. A total of 619 rodents and 554 pooled ectoparasites (287 mite pools, 62 flea pools, 35 louse pools, and 170 tick pools) were collected from 8 provinces within 4 regions of Thailand. <i>Bandicota indica</i> (279), <i>Rattus rattus</i> (163), and <i>R</i>. <i>exulans</i> (96) were the most prevalent species of rats collected in this study. Real-time PCR assay targeting <i>Bartonella</i>-specific <i>ssr</i>A gene was used for screening and each positive sample was confirmed by PCR using <i>nuo</i>G gene. The prevalence of <i>Bartonella</i> DNA in rodent (around 17%) was recorded in all regions. The highest prevalence of <i>Bartonella</i> species was found in <i>B</i>. <i>savilei</i> and <i>R</i>. <i>rattus</i> with the rate of 35.7% (5/14) and 32.5% (53/163), respectively. High prevalence of <i>Bartonella</i>-positive rodent was also found in <i>B</i>. <i>indica</i> (15.1%, 42/279), and <i>R</i>. <i>norvegicus</i> (12.5%, 5/40). In contrast, the prevalence of <i>Bartonella</i> species in ectoparasites collected from the rats varied significantly according to types of ectoparasites. A high prevalence of <i>Bartonella</i> DNA was found in louse pools (<i>Polyplax</i> spp. and <i>Hoplopleura</i> spp., 57.1%) and flea pools (<i>Xenopsylla cheopis</i>, 25.8%), while a low prevalence was found in pools of mites (<i>Leptotrombidium</i> spp. and <i>Ascoschoengastia</i> spp., 1.7%) and ticks (<i>Haemaphysalis</i> spp., 3.5%). Prevalence of <i>Bartonella</i> DNA in ectoparasites collected from <i>Bartonella</i>-positive rodents (19.4%) was significantly higher comparing to ectoparasites from <i>Bartonella</i>-negative rodents (8.7%). The phylogenetic analysis of 41 <i>glt</i>A sequences of 16 <i>Bartonella</i> isolates from rodent blood and 25 <i>Bartonella</i>-positive ectoparasites revealed a wide range of diversity among <i>Bartonella</i> species with a majority of sequences (61.0%) belonging to <i>Bartonella elizabethae</i> complex (11 rodents, 1 mite pool, and 5 louse pools), while the remaining sequences were identical to <i>B</i>. <i>phoceensis</i> (17.1%, 1 mite pool, 5 louse pools, and 1 tick pool), <i>B</i>. <i>coopersplainensis</i> (19.5%, 5 rodents, 1 louse pool, and 2 tick pools), and one previously unidentified <i>Bartonella</i> species (2.4%, 1 louse pool).</p></div

Phylogenetic relationship between <i>glt</i>A sequences of <i>Bartonella</i> species.

<p><i>Bartonella</i> species detected from rodents and their associated ectoparasites; mite (M), flea (F),tick (T), and louse (L), along with reference sequences (GenBank accession numbers are noted after each sequence). Only bootstrap replicates of >50% are shown. The <i>Bartonella</i> species detected in this study are indicated in bold letters.</p

Prevalence of <i>Bartonella</i> DNA among wild-caught rodents and their associated ectoparasites collected from different regions and provinces in Thailand, 2012–2013.

<p>^a<i>Bartonella</i> DNA was detected by <i>ssr</i>A and <i>nuo</i>G genes. The positivity for each sample was recorded only when 2 assays produced the concordant results.</p><p>^# Two <i>B</i>. <i>indica</i> rats had 2 positive tick pools.</p><p>^£ One <i>R</i>. <i>exulans</i> had 2 positive flea pools.</p><p>Prevalence of <i>Bartonella</i> DNA among wild-caught rodents and their associated ectoparasites collected from different regions and provinces in Thailand, 2012–2013.</p

Timing of Specimen Collection for Blood Cultures from Febrile Patients with Bacteremia▿

Bloodstream infections are an important cause of morbidity and mortality. Physician orders for blood cultures often specify that blood specimens be collected at or around the time of a temperature elevation, presumably as a means of enhancing the likelihood of detecting significant bacteremia. In a multicenter study, which utilized retrospective patient chart reviews as a means of collecting data, we evaluated the timing of blood culture collection in relation to temperature elevations in 1,436 patients with bacteremia and fungemia. The likelihood of documenting bloodstream infections was not significantly enhanced by collecting blood specimens for culture at the time that patients experienced temperature spikes. A subset analysis based on patient age, gender, white blood cell count and specific cause of bacteremia generally also failed to reveal any associations