A Radiolabeled Self-assembled Nanoparticle Probe for Diagnosis of Lung-Metastatic Melanoma.

Melanoma is a highly malignant skin cancer that frequently metastasizes to the lung, bone, and brain at an early phase. Therefore, noninvasive detection of metastasized melanoma could be beneficial to determine suitable therapeutic strategies. We previously reported a biocompatible ternary anionic complex composed of plasmid DNA (pDNA), polyethyleneimine (PEI), and γ-polyglutamic acid (γ-PGA) based on an electrostatic interaction, which was highly taken up by melanoma cells (B16-F10), even if it was negatively charged. Here, we developed a radiolabeled γ-PGA complex by using indium-111 (111In)-labeled polyamidoamine dendrimer (4th generation; G4) instead of pDNA and iodine-125 (125I)-labeled PEI instead of native PEI, and evaluated its effectiveness as a melanoma-targeted imaging probe. This ternary complex was synthesized at a theoretical charge ratio; carboxyl groups of 111In-diethylenetriaminepentaacetic acid (DTPA)-G4 : amino groups of 125I-PEI : carboxyl groups of γ-PGA was 1 : 8 : 16, and the size and zeta potential were approximately 29 nm and -33 mV, respectively. This complex was taken up by B16-F10 cells with time. Furthermore, a biodistribution study, using normal mice, demonstrated its accumulation in the liver, spleen, and lung, where macrophage cells are abundant. Almost the same level of radioactivity derived from both 111In and 125I was observed in these organs at an early phase after probe injection. Compared with the normal mice, significantly higher lung-to-blood ratios of radioactivity were observed in the B16-F10-lung metastatic cancer model. In conclusion, the radiolabeled γ-PGA complex would hold potentialities for nuclear medical imaging of lung metastatic melanoma.

Power Function Retention of Radionuclides in a Wound.

NCRP Report 156 describes soluble radionuclide retention kinetics in a wound, segregated into four retention categories: weak (W), moderate (M), strong (S), and avid (A). An alternate single-parameter model, the negative power function, t, is presented in this paper to describe the time behavior of radionuclide retention. With this mathematical description, γ is a single parameter that can be used to assign the wound retention category rapidly. Using the power function description of wound retention, the various wound categories present as straight lines on log scales with different slopes corresponding to the various retention categories. Regression analysis of average retention values in NCRP 156 shows γ = 0.735 ± 0.132, 0.514 ± 0.015, 0.242 ± 0.016, and 0.053 ± 0.023 for the weak, moderate, strong, and avid categories, respectively. A case study is presented (REAC/TS Registry case 1284) where a power function is shown to fit retention data in a Pu/Am hand wound up to 2,000 d (5.4 y) post-accident.

Significance of nuclear medicine scan in comparison with diethylenetriamine pentaacetic acid and ultrasound imaging in diagnosing renal disorders: An observational study.

The effectiveness of diethylenetriamine pentaacetic acid scan is regularly monitored for the assessment of any potential modifications in treatment responses or kidney functions in the pediatric population.This study attempts to compare the usefulness of diethylenetriamine pentaacetic acid and ultrasound imaging of renal disorders among paediatric patients.A retrospective observational study was conducted by enrolling 106 children. The demographic details such as: participant's age, gender, and the history of renal disease of each patient were recorded. Patients were administered radiopharmaceuticals in a fixed dose and were later subjected to computed tomography (CT) scan. The obtained data was analysed using descriptive statistics.Findings indicated increased sensitivity for CT (61.20%); whereas, a major decrease in specificity (23.68%) was observed. Comparison of Single-photon emission CT (SPECT) and CT findings revealed the increased sensitivity (90.90%) for ultrasound; whereas, there was a slight decrease in the specificity (40%) for SPECT. However, SPECT findings show 91% sensitivity among patients with 71.42% positive predictive value. Moreover, an increase in sensitivity for CT (61.20%), followed by a major decrease in specificity (23.68%) was observed.Ultrasonography has been proved to be the safest and the most effective method for the diagnosis and the treatment of most renal disorders, due to the higher predictive value of SPECT scans. It is thus suggested that patients with ureteral calculi should be diagnosed with renal scintigraphy and unenhanced helical computerized tomography.

Chelation Treatment by Early Inhalation of Liquid Aerosol DTPA for Removing Plutonium after Rat Lung Contamination.

Occupational contamination is a potential health risk associated with plutonium inhalation. DTPA remains the chelating drug of choice to decorporate plutonium. In this study, plutonium was found to be more effectively removed from lungs by a single inhalation of nebulized DTPA solution at only 1.1 µmol.kg-1 than by a single intravenous (i.v.) dose of DTPA at 15 µmol.kg-1. When DTPA was inhaled promptly after contamination, it removed the transportable fraction of plutonium prior blood absorption, thereby preventing both liver and bone depositions. Conversely, DTPA injection was better than inhalation at reducing the extrapulmonary burden, probably due to the much greater circulating dose, favoring the mobilization of plutonium already translocated. Thus, prompt inhalation, concomitantly supplemented with i.v. injection, of DTPA induced an important decrease in extrapulmonary deposits. Repeated DTPA inhalations over several weeks were more efficient than a single inhalation in limiting both pulmonary and extrapulmonary plutonium retention, due at least in part to the chelation of the transportable fraction of lung plutonium. Furthermore, repeated DTPA injections remained better at reducing liver and bone plutonium retentions. Taken together, our results suggest that multiple DTPA inhalations may be considered an effective treatment after inhalation of plutonium, particularly given the ease of this needle-free delivery, for the two following conditions: 1. A treatment combining i.v. injection and inhalation should be given in an emergency scenario to efficiently chelate the activity already absorbed; 2. Inhalations should be administered daily to effectively trap the early transferable fraction.

Measuring the Pancreatic ß Cell Mass in Vivo with Exendin SPECT during Hyperglycemia and Severe Insulitis.

OBJECTIVE: Targeting the glucagon-like peptide-1 receptor with radiolabeled exendin is a very promising method to noninvasively determine the ß cell mass in the pancreas, which is needed to unravel the pathophysiology of type 1 and type 2 diabetes. The present study aimed to explore the effects of both hyperglycemia and insulitis on the uptake of exendin in a spontaneous type 1 diabetes mouse model, nonobese diabetic (NOD) mice. METHODS: NOD mice (n = 75, 7-21 weeks old) were injected intravenously with [111In]In-DTPA-exendin-3, and single-photon emission computed tomography (SPECT) images were acquired 1 h pi. The pancreatic accumulation of [111In]In-DTPA-exendin-3 was quantified in vivo using SPECT and by ex vivo counting and correlated to the ß cell mass (BCM). The influence of insulitis and hyperglycemia on the exendin uptake was assessed. RESULTS: The pancreas could be visualized longitudinally using SPECT. A linear correlation was found between the BCM (%) and pancreatic uptake (%ID/g) as measured by ex vivo counting (Pearson r = 0.64, p < 0.001), which was not affected by either insulitis (Pearson r = 0.66, p = 0.83) or hyperglycemia (Pearson r = 0.57, p = 0.51). Biodistribution and ex vivo autoradiography revealed remaining [111In]In-DTPA-exendin-3 uptake in the pancreas despite total ablation of BCM. CONCLUSIONS: Despite hyperglycemia and severe insulitis, we have found a good correlation between BCM and pancreatic exendin uptake, even in a suboptimal model with relatively high background activity.

Equilibrium, affinity, dissociation constants, IC5O: Facts and fantasies.

The interaction between ligands and receptors is often described in terms of 50% inhibitory concentrations (IC50). However, IC50 values do not accurately reflect the dissociation constants (Kd), and the domain of application and precision of proposed approximations for Kd estimation are unclear. The effect of affinity and of experimental conditions on the differences between IC50 and Kd has been assessed from exact mass action law calculations and from computer simulations. Competitions between [111 In]DTPA-indium and a few metal-DTPA complexes for binding to a specific antibody are discussed as a practical example. Exact calculations of competition assays have been implemented in Microsoft Excel and performed for a variety of concentrations of receptor, tracer, and competitor. The results are identical to those of software packages. IC50 is found larger than Kd by less than 20% only when tracer concentration is small compared with Kd and to the receptor concentration and when this receptor concentration is small compared with Kd. Otherwise, Kd and IC50 may be very different and approximations proposed in the literature to obtain Kd values from graphically derived IC50 are not acceptable as soon as the concentrations of tracer or of receptor approach Kd. Under most experimental conditions, IC50 values do not reflect Kd values. Using available software packages to determine and report Kd values would allow for more meaningful comparisons of results obtained under different experimental conditions.

Radiosynthesis, radiochemical, and biological characterization of 177 Lu-labeled diethylenetriamine penta-acetic acid.

Diethylenetriamine penta-acetic acid (DTPA), when complexed with a gamma (γ)-emitter radioisotope like 99m Tc, is used for renal function diagnosis and many other diagnostic applications. The main aim of this study was to develop a novel and versatile single-step methodology for the synthesis of a new 177 Lu-labeled radiopharmaceutical with high radiochemical yield, which can be used for diagnostic purposes and therapeutic purposes also. The single and well-defined 177 Lu-DTPA complex was radiochemically characterized by paper chromatography, thin-layer chromatography, high-performance liquid chromatography, and electrophoresis techniques. Dependence of the labeling yield of 177 Lu-DTPA complex on different factors was studied in detail. Biological evaluation was also performed in a normal rabbit by developing images under a γ camera at various time intervals. More than 99% labeling yield was obtained by reacting DTPA with 177 Lu at specific conditions (pH 7.0, 15 minutes reaction time at 100 °C). 177 Lu-DTPA complex showed high stability both at room temperature and in vitro. Biodistribution studies in normal mice indicated the fractional renal uptake of intravenously administered 177 Lu-DTPA complex, which reached in the kidneys within 2-3 minutes. Scintigraphy showed rapid clearance from the body. Based on these results, we propose that 177 Lu-DTPA complex might be used as an ideal candidate for functional evaluation of kidneys and the urinary tract, especially when needed to be transported to long-range consumer sites, because of its suitable half-life.

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls.

BACKGROUND: For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3-4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited. METHODS: Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms. In addition, a retrospective evaluation of uptake on historical 111In-DTPA-octreotide scans was performed in patients with detectable tumor size > 1 cm. RESULTS: Over the last 17 years, 10 MTC patients were treated with PRRT. Four out of 10 patients showed stable disease at first follow-up (8 months after start of therapy) whereas the other 6 were progressive. Patients with stable disease were characterized by a combination of both a high uptake on 111In-DTPA-octreotide scan (uptake grade ≥ 3) and a positive somatostatin receptor type 2a (SSTR2a) expression of the tumor by immunohistochemistry. Retrospective evaluation of historical 111In-DTPA-octreotide scans of 35 non-treated MTC patients revealed low uptake (uptake grade 1) in the vast majority of patients 31/35 (89%) with intermediate uptake (uptake grade 2) in the remaining 4/35 (11%). CONCLUSIONS: PRRT using 177Lu-octreotate could be considered as a treatment in those patients with high uptake on 111In-DTPA-octreotide scan (uptake grade 3) and positive SSTR2a expression in tumor histology. Since this high uptake was present in a very limited number of patients, this treatment is only suitable in a selected group of MTC patients.

Impact of chelation timing on gadolinium deposition in rats after contrast administration.

OBJECTIVE: To determine if gadolinium (Gd) can be rechelated once released from Gd-based contrast agents (GBCAs) and deposited in vivo. Despite extensive research comparing GBCAs and GBCA formulations as well as the ongoing debate about their risks of deposition and the role of Gd release, it remains unknown if retained Gd can be eliminated by administering chelating agents. MATERIALS AND METHODS: Rats were injected intravenously with 10 doses of 1 mmol/kg gadodiamide and treated with intravenous Zn-DTPA (30 µmol/kg) concomitantly or 1, 4 or 8 h after GBCA administration (N = 3 rats per group). After euthanization, tissues were harvested three days after the last dose of gadodiamide and tissue Gd concentrations were assessed by ICP-MS. Additionally, a simulation of a single 0.1 mmol/kg gadopentetate dose with 30 µmol/kg DTPA given either concomitantly or within the first 24 h after GBCA was run; simulated tissue Gd concentrations were compared with those observed in rats to determine if simulated trends were accurate. RESULTS: Concomitant DTPA did not produce a significant reduction in Gd concentration in any organ for rats. There was a time-dependent trend in liver Gd reduction. The 1 h timepoint was associated with a non-significant increase in kidney, brain and femur Gd relative to untreated controls. There were no significant deviations from the model-predicted Gd changes. DISCUSSION: Both the simulation and rat study did not identify major benefits for chelation at the doses given, despite the simulation assuming all Gd deposited in tissues is unchelated. The potential redistribution in the rat study provide a compelling result that may impact the clinical relevance of further work investigating rechelation of Gd. Future work should further describe the three-dimensional dose-time-response relationship for preventing Gd deposition, and how that relates to long-term Gd toxicities.

Improved Modeling of Plutonium-DTPA Decorporation.

Individuals with significant intakes of plutonium (Pu) are typically treated with chelating agents, such as the trisodium salt form of calcium diethylenetriaminepentaacetate (CaNa3-DTPA, referred to hereafter as Ca-DTPA). Currently, there is no recommended approach for simultaneously modeling plutonium biokinetics during and after chelation therapy. In this study, an improved modeling system for plutonium decorporation was developed. The system comprises three individual model structures describing, separately, the distinct biokinetic behaviors of systemic plutonium, intravenously injected Ca-DTPA and in vivo-formed Pu-DTPA chelate. The system was linked to ICRP Publication 100, "Human Alimentary Tract Model for Radiological Protection" and NCRP Report 156, Development of a Biokinetic Model for Radionuclide-Contaminated Wounds and Procedures for Their Assessment, Dosimetry and Treatment." Urine bioassay and chelation treatment data from an occupationally-exposed individual were used for model development. Chelation was assumed to occur in the blood, soft tissues, liver and skeleton. The coordinated network for radiation dosimetry approach to decorporation modeling was applied using a chelation constant describing the secondorder, time-dependent kinetics of the in vivo chelation reaction. When using the proposed system of models for plutonium decorporation, a significant improvement of the goodness-of-fit to the urinary excretion data was observed and more accurate predictions of postmortem plutonium retention in the skeleton, liver and wound site were achieved.

Using 99mTc-DTPA galactosyl human serum albumin liver scintigraphy as a prognostic indicator in jaundice-free patients with biliary atresia.

BACKGROUND: We evaluated the clinical significance of follow-up data, including 99mTc-DTPA galactosyl human serum albumin (99mTc-GSA) liver scintigraphy data, as prognostic indicators for jaundice-free patients with biliary atresia (BA). METHODS: Of 87 patients who underwent Kasai portoenterostomy (KP) between 1991 and 2012, 45 jaundice-free patients aged 1-2 years underwent 99mTc-GSA scintigraphy and were classified into 2 groups: those who survived with a native liver (Group A, n = 34) and those who required liver transplantation (LTx) (Group B, n = 11). We compared 99mTc-GSA scintigraphy data (HH15, LHL15, and HH15/LHL15 [H/L15]) and liver function test (LFT) results between the groups. The patients underwent a second 99mTc-GSA scintigraphy at approximately 5 years of age. RESULTS: All patients survived. HH15, H/L15, total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, and alanine transaminase levels were higher in Group B than in Group A (p<0.05). Total and direct bilirubin levels were associated with H/L15 (p<0.05). There were no significant changes in results between the first and second 99mTc-GSA scintigraphy in Group A. CONCLUSIONS: Mid- and long-term prognoses may be predicted using 99mTc-GSA scintigraphy data and LFTs in patients aged 1-2 years. We recommend regular monitoring of postoperative data following KP, even in jaundice-free patients. LEVEL OF EVIDENCE: III.

Facile marriage of Gd3+ to polymer-coated carbon nanodots with enhanced biocompatibility for targeted MR/fluorescence imaging of glioma.

Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd-DTPA. Meanwhile, NCDDG reserved the bright fluorescence of biocompatible carbon nanodots with increased spatial resolution. Attributed to small size and hydrophilic polymer coating, NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls into surrounding glioma tissues via prolonged in vivo circulation and enhanced retention effect. As a result, dual1-modal targeted MR/fluorescence imaging of glioma was synergistically achieved with high sensitivity and resolution. This work promised a potential contrast agent for sensitive clinical diagnosis of glioma.

ENCAPSULATED 3,4,3-LI(1,2-HOPO) IN CHITOSAN NANOPARTICLES FOR DECORPORATION VIA INHALATION.

3,4,3-LI(1,2-HOPO) has been identified as an excellent alternative for DTPA for decorporating actinides, such as Pu and Am, after internal contamination. Efforts have been focused on its application through oral administration. When 3,4,3-LI(1,2-HOPO) was encapsulated with biocompatible, biodegradable nanoparticles made of chitosan, its release from the nanoparticles to lung fluid, observed in in vitro experiments, exhibited an extended release profile. These observations were very encouraging, as this nanomedicine could lead to a reduction in the dosing frequency required to achieve the decorporation efficacy of unformulated 3,4,3-LI(1,2-HOPO) itself. In vivo release tests as well as actinide decorporation experiments, using an inhalation exposure animal model, will follow.

AN ACCIDENT OF INTERNAL CONTAMINATION WITH PLUTONIUM AND AMERICIUM AT A NUCLEAR FACILITY IN JAPAN: A PRELIMINARY REPORT AND THE POSSIBILITY OF DTPA ADMINISTRATION ADDING TO THE DIAGNOSIS.

This article introduces the first accident of internal contamination with plutonium (Pu) or americium (Am) in Japan for which treatment was carried out. An accident of internal contamination with Pu and Am occurred at a Pu research facility at Oarai-town of Ibaraki prefecture in Japan. A plastic bag containing these radionuclides ruptured when five workers were inspecting a storage container in a hood. As a consequence, these workers were internally contaminated with Pu and Am. Although contamination on the body surface was observed in all five workers, a positive nasal swab was detected in only three of them. A chelating agent, calcium diethylenetriaminepenta-acetate (CaDTPA), was administered to all of them including the two workers without a positive nasal swab. However, bioassay detected a significant amount of Pu and Am in urine after administration of DTPA in these two workers, whereas the levels of these nuclides were below minimum detectable levels in urine before the administration. Since the prevalence of adverse reactions in DTPAs is low, the present results suggest that administration of DTPA can be used for the diagnosis of internal contamination even when a nasal swab is negative or contamination around body orifices is not detected.

Should DTPA, an Aminocarboxylic acid (ethylenediamine-based) chelating agent, be considered a developmental toxicant?

Aminocarboxylic acid (ethylenediamine-based) chelating agents, such as DTPA and EDTA, are widely used in a variety of products and processes. Recently the European RAC proposed to classify DTPA as a developmental toxicant Category 1B according to CLP. This paper provides unequivocal and significant evidence that developmental effects cannot be considered an intrinsic property of the chelating substances themselves since: (1) animals fed a zinc deficient diet during gestation exhibit developmental toxicity of a similar nature and severity to that observed in studies involving such chelates, (2) sufficient supplementation of zinc in the diet, or administration of zinc bound chelates, completely negates the developmental effects. Moreover, the bioavailability of DTPA is very low with >95% of oral doses excreted unchanged via the feces within 24 h. If DTPA would possess the intrinsic property to be developmentally toxic, simple zinc supplementation should not be sufficient to negate these effects. Furthermore, the relevance of classification is highly questionable since worker or consumer exposure could not lead to a scenario whereby sufficient zinc deficiency would manifest itself. Therefore classification of DTPA for such effects is not protective of human health; instead it leads to onerous and disproportionate restrictions being placed on this substance.

Actinide-contaminated Skin: Comparing Decontamination Efficacy of Water, Cleansing Gels, and DTPA Gels.

Skin contamination by alpha-emitting actinides is a risk to workers during nuclear fuel production and reactor decommissioning. Also, the list of items for potential use in radiological dispersal devices includes plutonium and americium. The actinide chemical form is important and solvents such as tributyl phosphate, used to extract plutonium, can influence plutonium behavior. This study investigated skin fixation and efficacy of decontamination products for these actinide forms using viable pig skin in the Franz cell diffusion system. Commonly used or recommended decontamination products such as water, cleansing gel, diethylenetriamine pentaacetic acid, or octadentate hydroxypyridinone compound 3,4,3-LI(1,2-HOPO), as well as diethylenetriamine pentaacetic acid hydrogel formulations, were tested after a 2-h contact time with the contaminant. Analysis of skin samples demonstrated that more plutonium nitrate is bound to skin as compared to plutonium-tributyl phosphate, and fixation of americium to skin was also significant. The data show that for plutonium-tributyl phosphate all the products are effective ranging from 80 to 90% removal of this contaminant. This may be associated with damage to the skin by this complex and suggests a mechanical/wash-out action rather than chelation. For removal of americium and plutonium, both Trait Rouge cleansing gel and diethylenetriamine pentaacetic acid are better than water, and diethylenetriamine pentaacetic acid hydrogel is better than Osmogel. The different treatments, however, did not significantly affect the activity in deeper skin layers, which suggests a need for further improvement of decontamination procedures. The new diethylenetriamine pentaacetic acid hydrogel preparation was effective in removing americium, plutonium, and plutonium-tributyl phosphate from skin; such a formulation offers advantages and thus merits further assessment.

Delivery of DTPA through Liposomes as a Good Strategy for Enhancing Plutonium Decorporation Regardless of Treatment Regimen.

In this study, we assessed the efficacy of unilamellar 110-nm liposomes encapsulating the chelating agent diethylenetriaminepentaacetic acid (DTPA) in plutonium-exposed rats. Rats were contaminated by intravenous administration of the soluble citrate form of plutonium. The comparative effects of liposomal and free DTPA at similar doses were examined in terms of limitation of alpha activity burden in rats receiving various treatment regimens. Liposomal DTPA given at 1 h after contamination more significantly prevented the accumulation of plutonium in tissues than did free DTPA. Also, when compared to free DTPA, liposome-entrapped DTPA was more efficient when given at late times for mobilization of deposited plutonium. In addition, repeated injections of liposomal DTPA further improved the removal of plutonium compared to single injection. Various possible mechanisms of action for DTPA delivered through liposomes are discussed. The advantage of liposomal DTPA over free DTPA was undoubtedly directly and indirectly due to the better cell penetration of DTPA when loaded within liposomes, mainly in the tissues of the mononuclear phagocytic system. The decorporation induced by liposomal DTPA may result first from intracellular chelation of plutonium deposited in soft tissues, predominantly in the liver. Afterwards, the slow release of free DTPA molecules from these same tissues may enable a sustained action of DTPA, probably mainly by extracellular chelation of plutonium available on bone surfaces. In conclusion, decorporation of plutonium can be significantly improved by liposomal encapsulation of DTPA regardless of the treatment regimen applied.

Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease: A Preliminary Report on 25 Patients.

OBJECTIVES: The aim of this study was to report the use of intravenous calcium (Ca)-/zinc (Zn)-diethylene triamine penta-acetic acid (DTPA) for the treatment of 25 symptomatic patients diagnosed with gadolinium deposition disease (GDD). MATERIALS AND METHODS: Written informed consent was obtained. Twenty-five patients (18 women; mean age, 46.8 ± 15.3 years) with a diagnosis of GDD were included. All patients had received at least 1 administration of a gadolinium (Gd)-based contrast agent. Patients received 3 treatment sessions with Ca-/Zn-DTPA, 15 with treatments spaced 1 month apart, and 10 with treatments spaced 1 week apart. In all cases, every treatment consisted of an application of Ca-DTPA and Zn-DTPA separated by 24 hours. Measurements of 24-hour urine Gd content before dosing and on the first and second days of therapy were performed. Symptomatic improvement of patients was determined by use of a 10-point scale of patient symptoms. Serum electrolytes were quantified. RESULTS: Gadolinium content increased in the urine, with an overall mean of 30.3-fold increase in the monthly regimen (P < 0.001) and 12.9-fold in the weekly regimen (P < 0.001). Eleven patients experienced transient worsening of at least some of their symptoms, termed a "flare-up" phenomenon, in most of whom symptoms improved or receded. Overall, symptoms improved in 13 patients, unchanged in 10, and worse in 2. Significant clinical improvement was present for headache, brain fog, and bone pain for the monthly regimen and arm pain and leg pain for the weekly regimen. There were no significant changes in major serum electrolytes. CONCLUSIONS: Three courses of intravenous Ca-/Zn-DTPA therapy results in significantly increased urine content of Gd after treatment and moderate symptomatic improvement.

Clinical Usefulness of Somatostatin Receptor Scintigraphy in Japanese Patients with Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND/AIMS: Somatostatin receptor (SSTR) scintigraphy (SRS) is the standard imaging modality for evaluation of gastroenteropancreatic neuroendocrine tumor (GEP-NET) in Western countries. However, this modality was not approved in Japan until recently. The purpose of this study was to evaluate the clinical efficacy of SRS for detecting GEP-NET in Japanese patients. METHODS: Japanese patients with advanced GEP-NET were enrolled and evaluated by the SRS and CT. We also compared SRS and immunohistochemical expression of SSTR type 2a (SSTR2a). RESULTS: We enrolled 16 patients and the primary sites were the pancreas in 9, the stomach in 1, the small intestine in 2, the colon in 3, and unknown in 1. SRS showed positive findings in 3 (100%) of grade 1 (G1) and in 12 (92.3%) of grade 2 (G2) lesions. In the liver, SRS and CT detected lesions in 13 and 14 cases, respectively. The concordance rate of SSTR2a expression with SRS findings was 93.8% in the whole body and 92.9% in the liver. CONCLUSIONS: SRS could detect almost all of G1 and G2. SRS could be useful to detect lesions, with a high concordance rate with CT and pathological findings. We confirmed that SRS is a useful and reliable modality for Japanese patients.