Evaluation of damage discrimination in dopaminergic neurons using dopamine transporter PET tracer [18F]FECNT-d4.

BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder worldwide, diagnosed based on classic symptoms like motor dysfunction and cognitive impairments. With the development of various radioactive ligands, positron emission tomography (PET) imaging combined with specific radiolabelling probes has proven to be effective in aiding clinical PD diagnosis. Among these probes, 2ß-Carbomethoxy-3ß-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl) nortropane ([18F]FECNT) has been utilized as a PET tracer to image dopamine transporter (DAT) integrity in striatal presynaptic dopaminergic terminals. However, the presence of brain-penetrant radioactive metabolites produced by [18F]FECNT may impact the accuracy of PET imaging. In previous research, we developed 2ß-Carbomethoxy-3ß-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl-1,1,2,2-d4) nortropane ([18F]FECNT-d4), a deuterated derivative with enhanced stability in plasma and the striatum, along with a slower washout rate. In this study, we further investigated the potential of [18F]FECNT-d4 to detect dopaminergic neuron degeneration in Parkinson's disease. This involved PET imaging in unilaterally-lesioned PD model rats and in vitro autoradiography conducted on postmortem brain sections. RESULTS: PET images revealed reduced specific uptake in the ipsilateral striatum of rats stereotactically injected with 6-hydroxydopamine hydrochloride (6-OHDA). Compared to the sham group, the ratio of standardized uptake value (SUV) in the ipsilateral to contralateral striatum decreased by 13%, 23%, and 63% in the mild, moderate, and severe lesioned groups, respectively. Dopaminergic denervation observed in PET imaging was further supported by behavioral assessments, immunostaining, and monoamine concentration tests. Moreover, the microPET results exhibited positive correlations with these measurements, except for the apomorphine-induced rotational behavior test, which showed a negative correlation. Additionally, [18F]FECNT-d4 uptake was approximately 40% lower in the postmortem striatal sections of a PD patient compared to a healthy subject. Furthermore, estimated human dosimetry (effective dose equivalent: 5.06 E-03 mSv/MBq), extrapolated from rat biodistribution data, remained below the current Food and Drug Administration limit for radiation exposure. CONCLUSION: Our findings demonstrate that [18F]FECNT-d4 accurately estimates levels of dopaminergic neuron degeneration in the 6-OHDA-induced PD rat model and effectively distinguishes between PD patients and healthy individuals. This highly sensitive and safe PET probe holds promising potential for clinical application in the diagnosis and monitoring of Parkinson's disease.

Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products.

Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE-xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu.

Bone mineral density, bone metabolism-related factors, and microRNA-218 are correlated with disease activities in Chinese ankylosing spondylitis patients.

OBJECTIVE: To investigate bone mineral density (BMD), bone metabolism-related factors, and microRNA-218 in Chinese ankylosing spondylitis (AS) patients and to identify their correlation with disease activities and the treatment with TNF-α inhibitors. METHODS: A total of 89 AS patients were enrolled in the study. Patients' information and laboratory examination results were collected. BMD of the anteroposterior lumbar spine (L2-L4), left femoral neck, and whole body were measured and T-scores were calculated. MicroRNA-218 was extracted from PBMCs of AS patients and detected by RT-PCR. Bone metabolism-related factors were detected using protein chips and flow cytometer. RESULTS: Out of 86 patients undergoing whole-body BMD measurement, 14 had osteopenia and 72 had normal BMD without osteoporosis or high BMD. Compared with short- (disease duration ≤3 years) and long-term groups (disease duration ≥10 years), medium-term group (disease duration ranges from 3 to 10 years) showed lowest BMD. Patients with onset age ≤20 years old had significantly lower BMD than the other groups (p < 0.05). The BMD of femoral neck had negative correlation with CRP (p < 0.05) and no correlation with BASDAI or ESR. Both whole-body BMD and femoral neck BMD were negatively correlated with BASMI (p < 0.05). Dickkopf-1 (DKK-1), platelet-derived growth factor-BB (PDGF-BB), and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) were significantly increased, while Osteopontin (OPN) was significantly decreased in AS patients. Expression of microRNA-218 in PBMC of AS patients was low and was positively correlated with BASMI (p < 0.05), but it was not correlated with the duration of disease, age of onset, BASDAI, ESR, or BMD. CONCLUSION: Loss of bone mass mainly occurred at the inflammatory sites in AS patients, depending on the severity of inflammation. The alleviation of inflammation can improve loss of bone mass and bone metabolism disorders. Anti-inflammatory treatment is critical for the treatment of secondary osteoporosis caused by AS.

Effects of advanced glycation end products on osteocytes mechanosensitivity.

Osteocytes are extremely sensitive to mechanical loading and govern bone remodeling process. Advanced glycation end products (AGEs) have the capacity to induce osteocyte apoptosis. In order to investigate the effects of AGEs on the mechanosensitivity of osteocytes, the osteocytic-like cells (MLO-Y4) were treated with low (50 µg/ml) and high (400 µg/ml) concentrations of AGEs for 1day and exposed to 15 dyne/cm2 of fluid shear stress. Then the F-actin cytoskeleton, prostaglandin E2(PGE2), Nitric oxide (NO), the Wnt/ß-catenin signaling pathway activity mRNA expressions were detected for osteocytes mechanical response changes; osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected for the regulation on bone remodeling function of osteocytes. The results showed that AGEs accumulation inhibited the sense of osteocytes to external mechincal loading, promoted shear-induced NO and PGE2 release, suppressed the mechanosensitivity of Wnt/ß-catenin signaling pathway, and furthermore promoted OCN and RANKL/OPG mRNA expressions. These indicated AGEs had an adverse impact on the mechanosensitivity of osteocytes, and led to a negative effect on their regulation of bone remodeling process under mechanical stimulation. This work provides a new perspective to interpret the alteration mechanism of osteocytes mechanosensitivity and provides a novel clue for exploring the mechanism of osteoporosis.

Efficacy and safety of 188Re-HEDP in lung cancer patients with bone metastases: a randomized, multicenter, multiple-dose phase IIa study.

PURPOSE: To investigate the pain-relieving effect and safety of three different doses of 188Re-hydroxyethylidine diphosphonate (HEDP) in patients with lung cancer and bone metastases. METHODS: For this randomised, phase 2 and multicenter trial, we enrolled patients with lung carcinoma and multifocal bone metastases and excluded patients who had received bisphosphonates or external-beam radiotherapy within the previous 4 weeks. Fifty-four patients were randomized to receive a single injection of 188Re-HEDP, at doses of 30, 40 or 50 MBq/kg (interval, 12 weeks). Patients were followed-up by assessment of numerical rating scale (NRS) score, global quality of life (QOL) score and adverse events (AEs). ANOVA analysis, Chi-Squared test and LSD-t test were used in this study. RESULTS: Significantly decreased NRS scores relative to baseline were observed in 40 MBq/kg group (Week 0 vs. Week 12: 6.0 ± 1.4 vs. 4.8 ± 2.5, P = 0.033) and 50 MBq/kg group (Week 0 vs. Week 12: 5.5 ± 1.5 vs. 4.5 ± 2.9, P = 0.046). Significant change of global QOL score from baseline was observed in 40 MBq/kg group at week 8 (global QOL score: P = 0.024, pain score: P = 0.041) and 50 MBq/kg group (pain score: P = 0.021) at week 12. No patients withdrew trial because of AEs in three groups. CONCLUSIONS: 188Re-HEDP at dose of 40 and 50 MBq/kg was generally effective to alleviate pain and improve QOL in lung cancer patients with painful bone metastases. 188Re-HEDP was safe and well-tolerated.

Phase I clinical study with different doses of 99mTc-TRODAT-1 in healthy adults.

OBJECTIVES: To study the pharmacokinetics, biodistribution, and injection doses of 99mTc-TRODAT-1 in healthy adults. METHODS: Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of 99mTc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively. RESULTS: No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that 99mTc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10-3 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10-3 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088). CONCLUSIONS: 99mTc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.

Correction to: A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson's disease.

The corresponding author of the article would like to remove "Jian Wang" in the author group.

A phase 2, open-label, multi-center study to evaluate the efficacy and safety of 99mTc-TRODAT-1 SPECT to detect Parkinson's disease.

OBJECTIVES: To assess the efficacy and safety of 99mTc-TRODAT-1 SPECT in diagnosing Parkinson's disease (PD). METHODS: 99mTc-TRODAT-1 SPECT imaging was performed in 34 healthy controls and 96 PD patients 2.5 h later after injection. The striatal image was evaluated visually and semi-quantitively. Sensitivity and specificity of 99mTc-TRODAT-1 SPECT were analyzed according to Hoehn and Yahr scale (HYS). Based on HYS, the PD patients were divided into mild (HYS 1-2) and moderate (HYS 3-5) groups. The uptake ratios of striatum (ST) and cerebellum (CB) in contralateral, ipsilateral and bilateral striatum in different groups were calculated and analyzed. The safety was assessed. RESULTS: The sensitivity and specificity of 99mTc-TRODAT-1 SPECT to discriminate PD patients from healthy subjects were 98.96% and 94.12% and it has perfect agreement with HYS (κ = 0.94, p < 0.001). The sensitivity to diagnose mild and moderate PD was 43.42% and 95% separately. The uptake ratio in PD patients was significantly lower than that in healthy controls (1.37 ± 0.13 vs 1.68 ± 0.18, p < 0.001). And the uptake ratio in contralateral side was markedly reduced in unilateral PD patients as compared with the ipsilateral side (1.50 ± 0.20 vs 1.46 ± 0.21, p < 0.001). The striatal uptakes in affected striatum and bilateral striatum were reduced with increasing disease severity between healthy control versus mild stage versus moderate stage in the affected striatum and bilateral striatum in PD patients. No serious adverse events or death was observed after injecting 99mTc-TRODAT-1. CONCLUSION: We demonstrated that 99mTc-TRODAT-1 was a safety radiotracer which can be used in clinic to diagnose PD using SPECT.

Evaluation of 99mTC-ECD SPECT/CT brain Imaging with NeuroGam analysis in Moyamoya disease after surgical revascularization.

To evaluate the clinical value of NeuroGam software in assessing the brain foci perfusion changes by TC-ECD single photon emission computed tomography/computed tomography (SPECT/CT) brain imaging in patients with Moyamoya Disease (MMD).Seventy-two patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with encephalo-duro-myo-synangiosis (EDMS) surgical revascularization were included. Baseline and follow-up TC-ECD SPECT/CT brain scans were performed on all patients at least twice before and after operation. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam Software package. Additional visual analysis was performed. Differences mean pixel value between pre- and post- operation brain perfusion were assessed with paired t test and McNemar test.Significant differences in the number of hypoperfusion foci were found between visual assessment and NeuroGam aided assessment. More hypoperfusion foci were found by NeuroGam software aided assessment in the frontal, parietal, temporal, occipital lobe, thalamus, basal ganglia and cerebellum before and after surgery (P < .0001). According to NeuroGam software assessment, the perfusion of frontal, parietal, temporal lobe, anterior and middle cerebral regions on the operative side significantly improved before and after surgery (t = -3.734, t = -3.935, t = -5.099, t = -4.006, t = -5.170, all P < .001). However, no significant differences were found in the occipital lobe (t = -1.962, P = .054), thalamus (t = 1.362, P = .177), basal ganglia (t = -2.394, P = .019), and cerebellum (t = 1.383, P = .171) before and after surgery.The NeuroGam software provides a quantitative approach for monitoring surgical effect of MMD in a variable time (3-12 months after surgery). It could discover the perfusion changes that are neglected in conventional visual assessment.

The comprehensive impact on human body induced by resolution of growth hormone excess.

CONTEXT: Chronic excess of growth hormone (GH) often leads to systemic complications. The reversibility of these complications after GH resolution is not fully understood. OBJECTIVE: To investigate when and to what extent will the comorbidities be ameliorated. DESIGN: We conducted a prospective study comprising 24 patients with acromegaly, who achieved remission after transsphenoidal surgery. The dynamic changes of endocrine, cardiovascular, respiratory, sleep, bone and morphology parameters were evaluated at enrollment and 1 week, 1 month, 3 months, 6 months and 12 months after surgery. RESULTS: Random GH dropped by 98.4% at the first day postoperatively. IGF-I index dropped by 50% and 64% at 1 week and 1 month respectively and remained unchanged onwards. Glucose metabolism improved significantly at 1 week and stabilized at 1 month. Testosterone in male patients recovered to normal range since 1 month. Systolic blood pressures dropped markedly at 3 months while diastolic blood pressures fell mildly at later visits. Abnormal lung function showed no improvement. The decrease of bone formation and resorption markers occurred at 1 week and 3 months, respectively. At 1 month, the tongue area declined while the airway volume increased significantly, accompanied with improved obstructive sleep apnea syndrome. Extremities, lips and nasal ala became smaller since 1 week. Liver, kidney and spleen volumes declined by 6.4, 15.9, 9.2%, respectively at 1 month. The volumes of pancreas and adrenal showed no change. CONCLUSIONS: The rapid resolution of excessive GH led to the reversible changes of systemic comorbidities in a time-dependent and organ-specific manner.

Assessment of the Bone Mineral Content in the Mandible by Dual-Energy X-Ray Absorptiometry to Evaluate Short-Term Change.

With the objective of being able to assess response to disease or clinical treatment, the densitometry community has long sought the ability to assess short-term change in bone density. The mandible, known to have a high bone turnover, an increased vascularity, and a greater susceptibility to osteoclastic and osteoblastic activities, has long been suggested but has fallen short as a site from which to monitor an early change in the response to a treatment or a disease. The current study developed a method to assess bone density in the superimposed left and right mandibles. Examining a skull in a positioning platform showed that studies between -5.0° and +12.5° from the preferred 0° orientation generated studies that were statistically similar to studies in the preferred orientation. After establishing the distribution of bone density in the mandibles, a software was developed that would execute a search for an area of intermediate content within the body and ramus regions of the mandible; in subsequent studies of the same individual, the analysis software would place the body and ramus regions in the same location without operator dependence. Studies in a population of subjects showed that the density in the body and ramus regions varied independently and that the density in these regions was independent of age. Repeat studies with repositioning showed repeatability of 1.73% and 2.44% for the body and ramus, resulting in computed least significant change limits of 4.84% for the body and 6.83% for the ramus. Examining 45 subjects undergoing treatment for osteoporosis up to over 46 wk showed 22 (49%) subjects with an increase in 1 of the mandible sites, suggesting a benefit from treatment, whereas 12 (27%) subjects showed a decrease in both mandible sites, suggesting a poor response to treatment. We conclude that applying the methodology and allowing the software to locate and define regions of interest allow assessments of change in the bone mineral content at the mandible that will reflect early changes occurring with disease or treatment.

Circulating Tumor Cells as a Biomarker in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Circulating tumor cells (CTCs) are valuable in both basic research and clinical application for cancer management. In the current study, we evaluated the diagnostic value of CTCs in pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 143 blood samples from 95 consecutively diagnosed PDAC patients and 48 healthy donors were collected. Combined data from immunostaining of CD45, DAPI and fluorescence in situ hybridization (FISH) with chromosome 8 centromere (CEP8) probe were used to identify CTCs. Cells with features of CD45-/DAPI+/CEP8>2 were detected as CTCs. RESULTS: CTCs were classified as triploid, tetraploid and multiploid based on chromosome 8 copy number. CTC subtype composition was significantly different among groups. Both subtype number and total CTC number were significantly increased in PDAC patients, compared to healthy controls. Total CTC number had 75.8% sensitivity and 68.7% specificity at a cutoff value of 2 cells/3.2 mL. This study is the first to report that CTC subtype number is also useful in cancer diagnosis. Sensitivity was 53.7% and specificity was 85.4% at a cutoff point of 2 CTC subtypes. The diagnostic value of both total CTC number and CTC subtype number was a little poorer than CA199. CONCLUSIONS: Both CTC subtype and total CTC number may serve as potential biomarkers for PDAC.

[Bone Tomography Scan Optimization in SPECT/CT Equipment of Nuclear Medicine].

Objective: To study and search for a balance between the image quality and acquisition speed in tomography of whole body bone scan. Methods: Adjustments of acquisition conditions were carried out gradualy every two months since April 2014. The qualities of fused SPECT/CT images were diagnosed by three doctors. Then the picture would be evaluated comprehensively by analyzing image quality and image resolution after adjusting image acquisition conditions. Results: Seven kinds of image acquisition conditions taken were in line with diagnostic requirements. The third method is extended to clinical work best. Conclusion: To obtain a high colection effi ciency, parameters of bone tomography acquisition can be set a frame of 5 seconds, total 64 (5.625o), automatic probe close and continuous scanning. Also recommends the use of "continuous" instead of "step and shoot" approach in bone SPECT acquisition. tomography, emission-computed, single-photon, bone tomography, program optimization.

Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence.

Single-photon emission-computed tomography (SPECT) after the administration of (99m)Tc-TRODAT-1 was performed on healthy subjects and subjects with methamphetamine (METH)dependence at time 1 (T1) after 24-48 h of abstinence, time 2 (T2) after 2 weeks of abstinence, and time 3 (T3) after 4 weeks of abstinence. In contrast to values in controls, the values of the striatal DAT specific uptake ratios (SURs) in subjects with METH dependence were significantly lower at T1 (n=25), T2 (n=9), and T3 (n=8); a mild increase in SURs was observed at T2 and T3, but values were still significantly lower than those in controls. In subjects with METH dependence, there was a trend for a negative correlation of striatal DAT SURs and craving for METH at T1. METH craving, anxiety and depression scores significantly decreased from T1 to T2 to T3. We conclude that Han Chinese people with METH dependence experience significant striatal DAT dysfunction, and that these changes may be mildly reversible after 4 weeks of abstinence, but that DAT levels still remain significantly lower than those in healthy subjects. The mild recovery of striatal DAT may parallel improvements in craving, anxiety and depression.

Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study.

PURPOSE: (177)Lu-labeled ethylenediamine-N,N,N',N'-tetrakis methylene phosphonic acid ((177)Lu-EDTMP), was used to palliate metastatic bone pain as a new bone-seeking radiopharmaceutical. In this phase II study, we assessed the efficacy and safety of (177)Lu-EDTMP for bone pain palliation in patients with breast cancer and hormone refractory prostate cancer with bone metastases. METHODS: Sixteen patients were enrolled in the trial and were subsequently divided into 2 groups, the low-dose group (1295 MBq) and the high dose group (2590 MBq) to determine differences in toxicities and response rates. Pain scores, Karnofsky indices, mobility scores, and requirement of analgesic administration were assessed at 0, 2, 4, 6, 8, and 12 weeks after injection of (177)Lu-EDTMP. Toxicity was assessed by analyzing hemoglobin, leukocyte, and platelet counts. RESULTS: An obvious reduction in the mean pain score was observed at 2 to 6 weeks after the administration of (177)Lu-EDTMP. The rate of complete responses in bone pain palliation was 55% in group 1 and 80% in group 2 at 6 weeks after treatment. Of the 5 patients who required additional analgesics, all were able to reduce or completely stop taking these medications by 4 weeks after therapy. Mean (SD) Karnofsky indices of 58.18 (9.82) (range, 50-70) and 56.00 (8.94) (range, 50-70) at baseline increased to 82.73 (9.05) (range, 60-90) at 6 weeks after (177)Lu-EDTMP treatment in group 1 and 85.00 (5.77) (range, 80-90) at 8 weeks after injection in group 2, respectively. Mobility scores decreased from 2.91 (1.04) (range, 1-4) and 2.80 (0.84) (range, 2-4) at baseline to 1.00 (0.67) (range, 0-2) and 0.50 (0.58) (range, 0-1) at 8 weeks after administration of (177)Lu-EDTMP in groups 1 and 2, respectively, primarily owing to improved mobility. In group 1, 1 patient experienced grade III toxicity in both hemoglobin and platelet counts. No grade IV toxicities were observed. In group 2, there were no grade III or IV toxicities found in hemoglobin, platelets, or leukocytes counts. Moreover, no clinically significant adverse effects were observed, and no significant differences in either efficacy or safety were detected between the 2 dose levels. CONCLUSIONS: This study indicated that (177)Lu-EDTMP was an effective and safe treatment for palliation of metastatic bone pain in patients with prostate or breast cancer. A dose of 1295 MBq (35 mCi) was sufficient for bone pain palliation therapy, and doses as high as 2590 MBq (70 mCi) were well tolerated.

Timing and optimized acquisition parameters for the whole-body imaging of ¹77Lu-EDTMP toward performing bone pain palliation treatment.

OBJECTIVES: Lutetium-177-labeled ethylenediamine-N,N,N',N'-tetrakis (methylene phosphonic acid) (¹77Lu-EDTMP), a beta-emitting bone-seeking therapeutic radiopharmaceutical being assessed as an agent for palliation of bone pain, can emit suitable gamma-photons for scintigraphy. This investigation sought to characterize its optimal conditions for whole-body gamma camera imaging in patients. MATERIALS AND METHODS: Eleven patients with bone metastases underwent whole-body bone scanning using both 99mTc-methyl-diphosphonate (99mTc-MDP) and ¹77Lu-EDTMP (29.4 ± 12.5 MBq/kg BW) utilizing a dual-head camera. For lutetium-177 imaging, two types of collimators, low-energy high-resolution (LEHR) and medium-energy general-purpose (MEGP), and two different peak energies of 113 and 208 keV were used. RESULTS: The femur-to-muscle uptake ratio (F/M) of 99mTc-MDP was 2.69 ± 1.06. For ¹77Lu-EDTMP, the significantly highest F/Ms were found at 24 h (12.59 ± 5.73) and 48 h (12.54 ± 5.23) by applying MEGP collimators and collecting the 208 keV photons. In all the combinations of collimator and peak energy, the F/Ms at 24 and 48 h are significantly higher than those at 1 h, except the combination of LEHR collimator and 208 keV peak energy. Lesion-to-normal bone uptake ratios of the 99mTc-MDP bone scan and images at the 24 and the 48-h phases of Lu-EDTMP were analyzed. MEGP and 208 keV had significantly higher values in lesion-to-normal bone uptake ratios. The combination of LEHR and 208 keV provided the poorest images. CONCLUSION: ¹77Lu-EDTMP can provide fine whole-body images with the best results when applying medium-energy collimation and collecting the 208 keV energy photons and alternatively by collecting both 208 and 113 keV photons for higher count statistics. The most appropriate time point for imaging is around 24 h after injection.