Yeast colonizing the intestine of rainbow trout (Salmo gairdneri) and turbot (Scophtalmus maximus)

Yeast were isolated from the intestine of farmed rainbow trout (Salmo gairdneri), turbot (Scophtalmus maximus), and free-living flat-fish (Pleuronectes platessa and P. flesus). The average number of viable yeasts recovered from farmed rainbow trout was 3.0 × 10³ and 0.5 × 10² cells per gram homogenized intestine for white and red-pigmented yeasts, respectively. The dominant species were Debaryomyces hansenii, Saccharomyces cerevisiae, Rhodotorula rubra, and R. glutinis. In 5 of 10 free-lving marine fish, > 100 viable yeast cells per gram intestinal mucus were recovered. Red-pigmented yeasts dominated and composed >90% of the isolates. Colonization experiments were performed by inoculating rainbow trout and turbot with fish-specific, isolated yeast strains and by examining the microbial intestinal colonization at intervals. Inoculation of experimental fish with pure cultures of R. glutinis and D. hansenii HF1 yielded colonization at a level several orders of magnitude higher than before the inoculation. Up to 3.8 × 10⁴, 3.1 × 10⁶, and 2.3 × 10⁹ viable yeast cells per gram intestine or feces were recovered in three separate colonization experiments. The high level of colonizing yeasts persisted for several weeks. The concentrations of yeasts in the tank water never exceeded 10³ viable cells per milliliter. No traces of fish sickness as a result of high yeast colonization were recorded during any of the colonization experiments. For periods of the experiments, the concentration of aerobic bacteria in the fish intestine was lower than the intestinal yeast concentration. Scanning electron microscopy studies demonstrated a close association of the yeasts with the intestinal mucosa. The mucosal colonization was further demonstrated by separating intestinal content, mucus, and tissue. All compartments were colonized by >10³ viable yeast cells per gram. No bacteria were detected on the micrographs, indicating that their affinity for the intestinal mucosa was less than that of the yeasts. Correspondence to: Thomas Andtid     

The role of l-arginine-nitric oxide pathway in bacterial translocation

This study investigated the nitric oxide (NO) role as a mediator of arginine on bacterial translocation (BT) and gut damage in mice after intestinal obstruction (IO). The effects of pretreatment with arginine with or without NO inhibition on the systemic and local immunological response were also assessed. Mice were categorized into four groups. Group ARG received chow containing 2 % arginine, while group ARG + l-NAME received the same diet plus l-NAME (N-nitro-l-arginine methyl ester) by gavage. The IO and Sham groups were fed standard chow. After 7 days, animals were gavaged with radiolabeled Escherichia coli, anesthetized and subjected to IO, except the Sham group. Animals were euthanized after 18 h, and BT was evaluated in the mesenteric lymph nodes, blood, liver, spleen and lungs. In another experiment, the intestinal injury was assessed regarding intestinal permeability and ileum histological analyses. Intestinal secretory immunoglobulin A (sIgA) levels, serum IFN-γ and IL-10 cytokines were assessed. Arginine reduced BT, but NO inhibition enhanced BT compared with the ARG group (p < 0.05). Intestinal permeability in the ARG and ARG + l-NAME groups was similar but decreased when compared with the IO group (p < 0.05). Histological preservation was observed. Arginine treatment increased IL-10 and sIgA levels when compared with the Sham and IO groups (p < 0.05). The cytokines and sIgA concentrations were similar in the ARG + l-NAME and Sham groups. Arginine appeared to reduce BT and its effects on the modulation of cytokines and secretory IgA in mice after IO are mediated by NO production.     

A developmental analysis of differences in the uptake of [123I]isopropyliodoamphetamine versus99mTc-pertechnetate by the choroid plexus and brain

The uptake of intravascular [¹²³I]isopropyliodoamphetamine (IMP) and^99mTc-pertechnetate into choroid plexus (CP) and brain (frontal cortex) was studied by an indicator fractionation method applied to immature, ketamine-anesthetized Sprague-Dawley rats (1.5, 2, and 3 wk). Assessment of the rate and extent of uptake of these indicators provides functional information (eg blood flow; transport) about various regions of the developing CNS. IMP uptake by lateral ventricle CP was 1.15 ml/g/min in 1.5-wk-old infant rats and gradually increased to 3.9 ml/g/min by adulthod (7–8 wk) (P<0.05); over the same postnatal period,^99mTc uptake went from 2.82 to 3.18 ml/g/min. IMP uptake by cortex was 0.39 and 0.99 ml/g/min in infants and adults, respectively (P<0.05); however,^99mTc uptake by cortex was only 0.07±0.01 ml/g/min at all ages, reflecting early development of blood-brain barrier (BBB) to pertechnetate. Overall, our findings indicated a progressive increase with age in the rate of uptake of IMP by CP and brain; and that^99mTc penetration into CP was relatively constant and substantially greater than into cortex at all developmental stages. Thus the nature of uptake of IMP, relative to^99mTc, was markedy different at the blood-cerebrospinal fluid barrier (i.e., CP) vs. the blood-brain barrier.     

Selection and Characterization of the Choline Transport Mutation Suppressor from Torpedo Electric Lobe,CTL1

The presumptive choline transporter, CTL1, was initially identified through functional complementation of a triple yeast mutant (ctr ise URA3) with deficiencies in both choline transport and choline neosynthesis under selective conditions that cause perturbations in membrane synthesis and growth. After transformation of these yeasts with a heterologous yeast expression library made from Torpedo electric lobe cDNAs, several colonies showed increased growth but only one clone increased the accumulation of external choline. The corresponding full-length cDNA was isolated and encodes a protein with 10 transmembrane domains. Northern analysis of Torpedo mRNA indicates that CTL1 is expressed at high levels in the spinal cord and brain. In Xenopus oocytes, Torpedo CTL1 expression was associated with the appearance of sodium independent high-affinity choline uptake. We propose that CTL1 plays a role in providing choline for membrane synthesis in the nervous system.     

Cellular and humoral immune responses to Candida albicans in subcutaneously infected mice

Pure mycelial and yeast cultures of Candida albicans were produced in a low sulphate medium. Groups of mice were injected subcutaneously with increasing doses of viable or heat-killed mycelial or yeast cells and the kinetics of delayed-type hypersensitivity (DTH), anti-mycelial and anti-yeast antibodies were studied. Both the dose and the morphological phase of C. albicans showed an influence on the development of the DTH, but the viability is the factor which showed the highest influence on this reaction, since on the one hand mice infected with viable yeast or mycelial cells developed higher DTH levels than mice injected with heat killed cells, and on the other hand this factor seems to play an important role in the kinetics of DTH response. The enzyme-linked immunosorbent assay has been adapted to detect antibodies to yeast and mycelial phase cytoplasmic antigens of C. albicans. In contrast with the DTH reactions, neither dose, morphological phase nor viability played an important role on the antibody titer developed. However, the use of mycelial cytoplasmic antigens seems to be better than the yeasts to detect anti -Candida antibodies over the last days studied.     

Comparative evaluation of 99mTc-labeled aminothiols as possible brain perfusion imaging agents

Several new ^99mTc aminodithiols were prepared and evaluated comparatively in experimental animals. The ligands were diamine, triamine or tetramine dithiols. Substituents were either attached on one of the nitrogens or introduced in between the two nitrogens of diamino dithiol (DADT) backbone. ^99mTc-derivatives prepared by coupling DADT to secondary amines via ethylene group showed in mice high initial brain uptake and significant retention in brain tissue. These preparations were mixtures of more than one ^99mTc-complex differing in brain uptake and clearance from the brain. The highest brain retention (brain to blood ratio 2.53, 15 min p.i.) was achieved with the ^99mTc-complex prepared by coupling DADT with ethylene pyrrolidine. Lengthening the chain between the nitrogens of DADT moiety by introducing methyl or amino alkyl groups resulted in ^99mTc-complexes with poor brain accumulation.     

Ultrastructural study ofCryptococcus neoformans by quick-freezing and deep-etching method

The three-dimensional ultrastructure ofCryptococcus neoformans was studied by quick-freezing and deep-etching (QF-DE) method.C. neoformans, strain CDC551, was cultured on agar. The viable yeast cells (10⁷ cells) were inoculated into each mouse from the tail vein. Three weeks after the inoculation, the brains of the mice were perfused with fixatives, quickly frozen, freeze-fractured, deeply etched and rotary shadowed with platinum and carbon. In addition, the viable cells ofC. neoformans on agar were picked up and quickly frozen, and replica membranes were prepared as described above. The ultrastructure ofC. neoformans was three-dimensionally demonstrated by the QF-DE method. The capsule was composed of fine meshworks of microfibrils (10–13 nm in diameter), which were directly attached to the cell walls. The capsule of the in vivo yeasts (yeast cells in the brain lesion) was thicker than that of the in vitro yeasts (yeast cells on agar culture). At the outer part of the cell wall, a particle-accumulating layer was observed. This layer in vivo was thicker than that in vitro. Occasionally, the yeast cells were ingested by phagocytes in the mouse brain. Although the cytoplasm of such yeast cells was destroyed, the capsular meshworks were well preserved. The ultrastructure of the capsule was the same both in cultured and phagocytized yeasts in the cystic lesions of the brains. This lack of morphological changes of the capsular meshworks suggests that they are resistant to the digestion by phagocytes. This stability of capsular structures may provide one of the important pathogenic factors in cystic lesions byC. neoformans.     

Effect of alterations in erythropoiesis on distribution of 99mTc sulfur colloid in the rat

The distribution of ^99mTc sulfur colloid and ⁵⁹Fe was assessed in rats following long or short term stimulation or suppression of erythropoiesis. Acute stimulation of erythropoiesis did not alter ^99mTc sulfur colloid distribution, whereas, long term stimulation resulted in increased marrow colloid uptake. Suppression of erythropoiesis by hypoxia-induced plethora or hypertransfusion did not alter the marrow uptake of ^99mTc sulfur colloid. ^99mTc sulfur colloid blood clearance was not altered by any of the experimental conditions utilized. These observations suggest that marrow RE activity as assessed by ^99mTc sulfur colloid uptake increases with erythropoietic stimulation and varies with the duration and intensity of the stimulus.     

Antibody-dependent difference in biodistribution of monoclonal antibodies in animal models and humans

 The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and humans, and to elucidate the applicability of animal models. ^99mTc-labeled murine mAb – against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150) – and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925 MBq, 1 mg). The biodistribution of two of the three mAb (not ^99mTc-BW431/26) differed clearly in mice and patients. ^99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination showed increased uptake in the liver with rapid blood clearance (mean α half-life = 31.1 min) compared with ^99mTc-BW431/26 (28.4 h). ^99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in tumors. Clinical examination showed rapid blood clearance (mean α half-life = 6.4 min) and increased uptake in the liver. High-performance liquid chromatographic analysis of ^99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb and interacting substances. Received: 9 April 1997 / Accepted 3 March 1998     

Synthesis,characterization and biodistribution of tris(β-diketonato)technetium(III) complexes

New tris(β-diketonato) complexes of trivalent ⁹⁹Tc/^99mTc with the ligands hexane-2,4-dione, heptane-2,4-dione, heptane-3,5-dione, and octane-3,5-dione were synthesized by reduction of pertechnetate with dithionite in the presence of excess β-diketone. The complexes were purified by HPLC, identified by elemental analysis and FAB mass spectrometry, and characterized by vis./u.v./i.r. spectrophotometry. The hexane-2,4-dionato complex crystallizes in the monoclinic space group P2₁/c, isostructurally with pentane-2,4-dionatotechnetium(III). Biodistribution measurements in mice showed the neutral and lipophilic ^99mTc-diketonato complexes to penetrate the blood-brain barrier. However, increasing lipophilicity decreased the brain uptake except for the heptane-2,4-dionato complex, which displayed the highest uptake of 0.82% injected dose/g.     

Phagocytic Cells in the Peripheral Blood of the Dogfish Scyliorhinus canicula L. II. In Vivo Studies

In vivo phagocytosis by peripheral blood leucocytes of the dogfish Scyliorhinus canicula L. was examined by monitoring the fate of a variety of injected materials, both particulate and soluble, in normal and immunised fish. Carbon, yeasts and bacteria were phagocytosed by monocytes, thrombocytes and type 1 granulocytes (neutrophils). Quantitative in vivo antigen clearance studies employed five species of bacteria, yeast and KLH. After an initial significant decrease of these antigens in the circulation, low numbers of viable bacteria and yeasts and low concentrations of KLH persisted for long periods after injection. Previous exposure to several of these antigens had little or no effect.     

99mTc- and Re-labeled 6-dialkylamino-2-naphthylethylidene derivatives as imaging probes for β-amyloid plaques

Based on the conjugate strategy, two neutral ^99mTc labeled 2-(1-(6-(dialkylamino)naphthalen-2-yl)ethylidene)malononitrile (DDNP) and 1-(6-(dialkylamino)naphthalen-2-yl)ethanone (ENE) derivatives, and their corresponding rhenium complexes were synthesized. In vitro fluorescent staining indicated that the corresponding rhenium derivatives selectively stained the β-amyloid (Aβ) plaques in the brain sections of AD model mice with low background. Compared with FDDNP and FENE, the affinities of the corresponding rhenium derivatives to Aβ aggregates decreased about 10-14-fold. In vivo biodistribution experiments in normal mice showed that ^99mTc-MAMA-ENE displayed medium initial brain uptake (0.65 %ID/g at 2 min) with a reasonable washout from the brain (0.19 %ID/g at 2 h) while ^99mTc-MAMA-DDNP showed a low brain uptake (0.28 %ID/g at 2 min). Further optimize these ^99mTc-labeled tracers in order to improve their binding affinities to Aβ plaques and diffusion through the blood brain barrier may generate useful imaging agents for SPECT.     

Biological distribution of 99mTc-labeled YIGSR and IKVAV laminin peptides in rodents: 99mTc-IKVAV peptide localizes to the lung

Two laminin-derived peptides containing either YIGSR or IKVAV (single amino acid code) sequences were radiolabeled with ^99mTc and their biological distribution evaluated in rodents. Both ^99mTC-peptides cleared rapidly from the circulation though the kidney, and to a lesser extent, through the liver. ^99mTC-YIGSR peptide did not accumulate in any organ examined in normal, tumored, and emphysemic mice. The ^99mTc-IKVAV peptide localized within 10 min to the lung of normal animals, resulting in lung-to-blood ratios of approximately 23:1. The ^99mTc-IKVAV peptide localized to lung after submicron filtration and after intraperitoneal injection, suggesting that particulates do not play a major role in localization. Pre-incubation of ^99mTc-IKVAV peptide in whole blood decreased lung localization, suggesting that margination of radiolabeled blood cells does not play a major role in the lung localization. When ^99mTc-IKVAV was injected into mice with tumored lungs (melanoma), the lung uptake was markedly increased (up to 20% injected dose higher than control lungs) at all time points examined (10, 30, and 120 min). When ^99mTc-IKVAV was injected into mice with genetic emphysema, the lung uptake was markedly decreased at all time points. The localization of the ^99mTc-IKVAV-containing peptide to the lung is consistent with a receptor-based mechanism.     

Digestion of Histoplasma capsulatum yeasts by human macrophages.

The strategies used by Histoplasma capsulatum yeasts to survive and multiply within human macrophages (M phi) are unknown. To better understand these strategies we studied the intracellular fate of viable vs heat-killed (HK) yeasts in human monocyte-derived M phi. Initial studies demonstrated that phagolysosome fusion was present in M phi ingesting either viable or HK yeasts. Viable yeasts multiplied within M phi phagolysosomes, whereas M phi completely digested intracellular FITC-labeled HK yeasts within 24 h after ingestion. This observation was confirmed by electron microscopy. M phi that had ingested colloidal gold-labeled HK yeasts contained gold particles but no visible yeasts at 24 h. Digestion of HK yeasts was evident as early as 4 h after phagocytosis, and was complete by 24 h. M phi digestion of HK yeasts was blocked completely when M phi were cultured for 24 h in the presence of chloroquine. In M phi simultaneously ingesting both viable and HK yeasts, viable yeasts multiplied, but HK yeasts were digested within the same cell. M phi that had ingested viable yeasts digested them completely when M phi were cultured for 24 h in the presence of cycloheximide or amphotericin B. Coculture of infected M phi with nystatin or ketoconazole resulted in inhibition of growth, but the yeasts were not digested. These data indicate that: 1), HK Hc yeasts are easily digested by preformed M phi lysosomal hydrolases; 2), viable Hc yeasts survive and multiply within M phi phagolysosomes, but the yeasts do not secrete a factor(s) that affects the ability of other phagolysosomes within the same M phi to digest killed yeasts; and 3), inhibition of yeast protein synthesis or cell wall biosynthesis is sufficient to render viable yeasts susceptible to digestion by human M phi.     

Multiple mechanisms may contribute to the adherence ofCandida yeasts to living cells

The adherence ofCandida yeasts to monolayers of human intestinal epithelium was studied in order to determine the specific and nonspecific mechanisms that might contribute to yeast adherence. Multiple factors were shown to significantly affect the adherence of yeasts to intestinal cells. It was demonstrated that hydrophobic yeasts adhered two times greater than normal yeasts, and positively charged yeasts adhered ten times greater than normal yeasts to monolayers of intestinal epithelium. The binding of yeasts to the intestinal cells was saturable and was most effectively blocked by mucin, which caused an 83% reduction in adherence, whereas the addition ofd-glucose caused a 41% reduction in adherence. Aggregation or coadherence of yeasts occurred as the yeast inocula were increased.Candida appears to possess the ability to adhere to living tissue by several mechanisms, such as adhesin-receptor interactions, nonspecific hydrophobic and ionic bonding, and aggregation or coadherence. This is the first demonstration of multiple forces that may act simultaneously in the process of adherence of yeasts to living cells.     

99mTc-tricarbonyl labeled agents for cell labeling: Development,biodistribution in normal mice and preliminary in vitro evaluation

We have developed four ^99mTc(CO)₃-labeled lipophilic tracers as potential radiolabeling agents for cells based on a hexadecyl tail. ^99mTc(CO)₃-hexadecylamino-N,N′-diacetic acid (negatively charged), ^99mTc(CO)₃-hexadecylamino-N-α-picolyl-N′-acetic acid (uncharged), ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine (positively charged), ^99mTc(CO)₃-N-hexadecylaminoethyl-N′-aminoethylamine (positively charged) were prepared in a radiolabeling yield: >90%. Preliminary cell uptake studies were performed in mixed blood cells with or without plasma and were compared with ^99mTc-d,l-HMPAO and [¹⁸F]FDG. In plasma-free blood cells, maximum uptake (78%) was obtained for ^99mTc(CO)₃-N-hexadecylaminoethyl-N′-aminoethylamine after 60 min incubation (compared to 55% and 23% for ^99mTc-d,l-HMPAO and [¹⁸F]FDG, respectively) while in plasma-rich medium, ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine was best bound (54%, similar to the binding of ^99mTc-d,l-HMPAO). Biodistribution in normal mice showed mainly hepatobiliary clearance of the agents and initial high lung uptake. The radiolabeled compounds showed good blood clearance with maximally 7.9% injected dose per gram at 60 min post injection. While the least lipophilic agent (^99mTc(CO)₃-N,N′-dipicolylhexadecylamine, log P = 1.3) showed the best cell uptake, there appears to be no direct correlation between lipophilicity and tracer uptake in mixed blood cells. In view of its comparable cell uptake to well known cell labeling agent ^99mTc-d,l-HMPAO, ^99mTc(CO)₃-N,N′-dipicolylhexadecylamine merits further evaluation as a potential cell labeling agent.     

Preparation,radiolabeling and biodistribution of a new class of bisaminothiol (BAT) ligands as possible imaging agents

In developing new ligands as potential brain and heart perfusion imaging agents two ligands based upon N₂S₂ donor atoms with the biphenyl backbone were synthesized. Biphenyl-2,2′-bis(N-1-amino-2-methyl-propane-2-thiol) (BP-BAT-TM) and biphenyl-2,2′-bis(N-1-amino-2-ethyl-butane-2-thiol) (BP-BAT-TE) form stable, neutral and lipid soluble complexes with [^99mTc]pertechnetate in the presence of tin(II) tartarate as a reducing agent. The [^99mTc]BP-BAT-TM complex penetrates the blood-brain barrier following i.v. injection into rats. Washout from the brain is fast, indicating no retention. The biodistribution of [^99mTc]BP-BAT-TE in rats showed an intitial heart uptake (0.8% /organ, at 2 min) and a slow washout (0.74% at 15 min). No brain uptake was found (0.05%). Significant uptake and retention in liver was observed. An imaging study of [^99mTc]BP-BAT-TE in a monkey showed no brain uptake and a clear indication of liver uptake and gall bladder clearance. These results indicate that this ligand system may be suitable as the basic core structure for the development of new imaging agents. Further studies with structural variations in the biphenyl backbone are warranted to develop new ^99mTc imaging agents for clinical applications.     

Changes in the intracellular concentrations of the adenosine phosphates and nicotinamide adenine dinucleotides ofSaccharomyces cerevisiae during batch fermentation

Significant changes in the intracellular concentrations of adenosine phosphates and nicotinamide adenine dinucleotides were observed during fermentation of grape must by three different strains ofSaccharomyces cerevisiae: S. cerevisiae var.cerevisiae, a typical fermentative yeast strain and two flor-veil-forming strains,S. cerevisiae var.bayanus andS. cerevisiae var.capensis. The intracellular concentration of ATP was always higher inS. cerevisiae var.cerevisiae than in the flor-veil-forming strains. NAD⁺ and NADP⁺ concentrations decreased at faster rates in the flor-veil-forming yeasts than in the other yeast but NADH concentration was the same in all yeasts for the first 10 days of fermentation. NADPH concentration was always lower inS. cerevisiae var.cerevisiae than in the other yeasts and this yeast also showed higher rates of growth and fermentation during the early stages of the fermentation and the presence of non-viable cells at the end of fermentation. In contrast, the flor-veil-forming strains maintained growth and fermentation capabilities for a relatively long time and viable cells were present throughout the entire fermentation process (31 days).The authors are with the Department of Microbiology, Faculty of Sciences, University of Cordoba, Avda. San Alberto Magno s/n, 14004-Córdoba, Spain     

Radiolabeling of lipid-based nanoparticles for diagnostics and therapeutic applications: a comparison using different radiometals

Radiolabeling of nanoparticles (NPs) has been performed for a variety of reasons, such as for studying pharmacokinetics, for imaging, or for therapy. Here, we describe the in vitro and in vivo evaluation of DTPA-derivatized lipid-based NP (DTPA-NP) radiolabeled with different radiometals, including ¹¹¹In and ^99mTc, for single-photon emission computed tomography (SPECT), ⁶⁸Ga for positron emission tomography (PET), and ¹⁷⁷Lu for therapeutic applications. PEGylated DTPA-NP with varying DTPA amounts, different composition, and size were radiolabeled with ¹¹¹In, ¹⁷⁷Lu, and ⁶⁸Ga, using various buffers. ^99mTc-labeling was performed directly and by using the carbonyl aquaion, [^99mTc(H₂O)₃(CO)₃]⁺. Stability was tested and biodistribution evaluated. High labeling yields (>90%) were achieved for all radionuclides and different liposomal formulations. Specific activities (SAs) were highest for ¹¹¹In (>4 MBq/μg liposome), followed by ⁶⁸Ga and ¹⁷⁷Lu; for ^99mTc, high labeling yields and SA were only achieved by using [^99mTc(H₂O)₃(CO)₃]⁺. Stability toward DTPA/histidine and in serum was high (>80 % RCP, 24 hours postpreparation).). Biodistribution in Lewis rats revealed no significant differences between NP in terms of DTPA loading and particle composition; however, different uptake patterns were found between the radionuclides used. We observed lower retention in blood (<3.3 %ID/g) and lower liver uptake (< 2.7 %ID/g) for ^99mTc- and ⁶⁸Ga, compared to ¹¹¹In-NP (blood, <4 %ID/g; liver, <3.6 %ID/g). Imaging potential was shown by both PET magnetic resonance imaging fusion imaging and SPECT imaging. Overall, our study shows that PEGylated DTPA-NP are suitable for radiolabeling studies with a variety of radiometals, thereby achieving high SA suitable for targeting applications.