Neopentyl Glycol as a Scaffold to Provide Radiohalogenated Theranostic Pairs of High In Vivo Stability.

The high in vivo stability of 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all 125I-labeled compounds remained stable against nucleophilic substitution, only a 125I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against in vivo deiodination. 211At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. 211At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the 125I/211At-labeled benzoate pair. The urine analyses confirmed that 211At-labeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [211At]At-. These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and 211At.

High-performance renal imaging with a radiolabeled, non-excretable chimeric fusion protein.

Ideal nuclear imaging tracers should exhibit high target uptake and low background signal. Traditional renal scintigraphy and SPECT scans examine kidney function via static or dynamic tracing of radioactive probes in the kidneys. The lack of tracer affinity to specific biological processes and high background uptake from urinary excretion have added many difficulties to precision renal diagnosis. In this issue of Theranostics, Jin and colleagues innovatively devised a recombinant probe for preferential kidney imaging through targeting of tubular neonatal Fc receptor and proximal tubular basement membrane for sustained tubular reabsorption and accumulation. This work has broad implications regarding how an in depth understanding of physiology and pathology may be of service for tracer development, renal diagnosis, and disease theranostics.

Development and characterization of two novel 68 Ga-labelled neuropeptide Y short analogues with potential application in breast cancer imaging.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.

Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [177Lu]Lu-PSMA-617.

In recent years, radiolabeled tracers targeting prostate-specific membrane antigen (PSMA) have had a tremendous impact on prostate cancer management. Here, we report on the formation of radioactive impurities formed during the clinical production of 177Lu-labeled PSMA-617. We provide compelling evidence that these impurities are the result of a spontaneous, thermally mediated condensation reaction of the Glu-CO-Lys moiety resulting in the formation of three different five-membered ring systems. Density functional theory (DFT) calculations show that the condensation and cyclization of the Glu-CO-Lys moiety is thermodynamically spontaneous. In cell experiments, no affinity of these cyclized compounds toward PSMA was observed. HPLC analyses of urine samples from patient studies showed rapid renal excretion of these radioactive cyclized species. Radiolabeling conditions were identified that significantly reduced the formation of cyclized side products yielding 177Lu-labeled PSMA-617 in high radiochemical yield and purity in concordance with current good manufacturing practice (cGMP) requirements.

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion.

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [18F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.

High detection rate in [18F]PSMA-1007 PET: interim results focusing on biochemical recurrence in prostate cancer patients.

OBJECTIVE: 18F-labeled prostate-specific membrane antigen (PSMA) ligand, [18F]PSMA-1007, has the benefit of a higher synthetic yield and minimal excretion in the urine. High detection efficacy was reported in biochemical recurrence (BCR) of prostate cancer after radical prostatectomy. Thus, we evaluated the preliminary diagnostic utility of [18F]PSMA-1007 PET in patients with prostate cancer, focusing on the BCR which is not detected on conventional imaging. METHODS: We enrolled a total of 28 patients (age 51-79 years) with BCR of prostate cancer. BCR was defined as a continuous increase in PSA after radical prostatectomy or radiation therapy without any apparent recurrent lesions on conventional diagnostic imaging (CT and bone scintigraphy). PSMA-PET scanning was performed approximately 60 min after intravenous injection of [18F]PSMA-1007 (259 ± 37 MBq). PSMA-PET images were evaluated for lesion detection as well as its relation to PSA values and location. RESULTS: Abnormal uptake, which was suspected to be recurrence or metastasis, was detected in 92.9% (26/28) of patients with BCR. The SUVmax was 8.4 ± 6.4 in local recurrence, 11.5 ± 11.8 in pelvic lymph nodes (LN), and 4.1 ± 1.6 in bone metastasis. The detection rates were 66.7% in the PSA group-1 (0.1-0.5 ng/mL), 85.7% in the PSA group-2 (0.5-1.0 ng/mL), and 100% in the PSA group-3 (above 1.0 ng/mL). Among the PET-positive BCR patients (n = 26), local recurrence was detected in 57.7% (15/26), pelvic LN in 42.3% (11/26), and bone metastasis in 15.4% (4/26). In 53% (8/15) of BCR patients who were suspected of local recurrence, focal uptake was detected adjacent to the bladder on [18F]PSMA-1007 PET. This suggested the significant advantage of having minimal physiological urine excretion. CONCLUSIONS: [18F]PSMA-1007 PET showed a high detection rate in recurrent and metastatic lesions. In patients with BCR, its high detection led to suitable treatment strategies, such as salvage radiation therapy or surgical removal of recurrent lymph nodes. TRIAL REGISTRATION: (UMIN Clinical Trials Registry) UMIN000037697.

Standardization of acquisition protocols using PET/CT with 18F-Choline in prostate cancer. / Estandarización de los protocolos de adquisición mediante PET/TC con 18F-Colina en el cáncer de próstata.

AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS: One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS: Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ20.91): -7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS: As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence.

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.

Does Delayed Excretion of Therapeutic 131I-MIBG Interfere with a 123I-MIBG Diagnostic Scan 6 Weeks After the Therapy?

131I-metaiodobenzylguanidine (131I-MIBG) is a theranostic agent useful for treatment of neuroendocrine malignancies. In this case, a child with a Curie score of 21 was administered 17.871 GBq (483 mCi) of 131I-MIBG. The elimination half-life progressively increased from 23 h to 77 h during the 11 d that the patient was hospitalized for radiation isolation. Six weeks after the posttherapy scan, a survey with an ion-chamber device yielded readings of 0.3 µSv/h (0.03 mR/h) on contact with spinal regions that had shown increased uptake on the scan. A planar image obtained using the 131I setting and a high-energy collimator did not demonstrate any focal uptake. 123I-MIBG was administered, and the 24-h scan was of diagnostic quality, without degradation from the remaining 131I-MIBG. Additional study is needed on whether the Curie score affects elimination of 131I-MIBG and on whether the period of hospitalized radiation isolation needs to be extended.

Absolute radiotracer concentration measurement using whole-body solid-state SPECT/CT technology: in vivo/in vitro validation.

The accuracy of recently approved quantitative clinical software was determined by comparing in vivo/in vitro measurements for a solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography/x-ray computed tomography) camera. Bone SPECT/CT, including the pelvic region in the field of view, was performed on 16 patients using technetium-99m methylene diphosphonic acid as a radiotracer. After imaging, urine samples from each patient provided for the measurement of in vitro radiopharmaceutical concentrations. From the SPECT/CT images, three users measured in vivo radiotracer concentration and standardized uptake value (SUV) for the bladder using quantitative software (Q.Metrix, GE Healthcare). Linear regression was used to validate any in vivo/in vitro identity relations (ideally slope = 1, intercept = 0), within a 95% confidence interval (CI). Thirteen in vivo/in vitro pairs were available for further analysis, after rejecting two as clinically irrelevant (SUVs > 100 g/mL) and one as an outlier (via Cook's distance calculations). All linear regressions (R2 ≥ 0.85, P < 0.0001) provided identity in vivo/in vitro relations (95% CI), with SUV averages from all users giving a slope of 0.99 ± 0.25 and intercept of 0.14 ± 5.15 g/mL. The average in vivo/in vitro residual difference was < 20%. Solid-state SPECT/CT imaging can reliably provide in vivo urinary bladder radiotracer concentrations within approximately 20% accuracy. This practical, non-invasive, in vivo quantitation method can potentially improve diagnosis and assessment of response to treatment. Graphical abstract.

Urinary Excretion of Yttrium-90 after Radioembolization with Yttrium-90-Labeled Resin-based Microspheres.

In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)-labeled resin microspheres, radiation protection is primarily concerned with avoiding contamination by radioactive spheres. However, as Y is bound to the microsphere surface by a potentially reversible ion-exchange process, the aim of this study was to assess the extent of the potential excreted activity in urine. After RET with Y-labeled resin-based microspheres, urinary excretion of free Y was prospectively analyzed in 51 interventions (n = 45 patients) by sampling urine over 48 h (two 24-h intervals) consecutively. The measured urinary concentration of Y, normalized to the administered microsphere activity, was a median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8-58.8 kBq L GBq) for the first and second 24-h periods after administration, respectively (p ≤ 0.0001, F = 28.4, result from ANOVA). The total excreted activity significantly decreased (p ≤ 0.0001) from a median of 72.5 kBq in the first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary excretion of free Y after resin-based RET occurs for a longer period and at a higher activity excretion than previously published, which has to be considered when patients are either hospitalized or return home after RET. Existing approaches for patient hospitalization, especially in temporary radiation protection areas, justified by the previously reported lower excretion rate, should be re-evaluated, and as a consequence, the current product safety information and handling recommendations for Y-labeled resin-based microspheres may need to be revised.

Evaluation of novel 111In-labeled gonadotropin-releasing hormone peptides for human prostate cancer imaging.

The purpose of this study was to evaluate the tumor targeting and imaging properties of novel 111In-labeled gonadotropin-releasing hormone (GnRH) peptides for human prostate cancer. Three new 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linker-d-Phe-(d-Lys6-GnRH) peptides with different hydrocarbon linkers were designed to evaluate their effects on GnRH receptor binding affinities. The Aoc (aminooctanoic acid) linker was better than ßAla (3-aminopropanoic acid) and Aun (aminoundecanoic acid) linkers in retaining strong receptor binding affinity. DOTA-Aoc-d-Phe-(d-Lys6-GnRH) exhibited 6.6±0.1nM GnRH receptor binding affinity. 111In-DOTA-Aoc-d-Phe-(d-Lys6-GnRH) exhibited fast tumor uptake and urinary clearance in DU145 human prostate cancer-xenografted nude mice. The DU145 tumor lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using 111In-DOTA-Aoc-d-Phe-(d-Lys6-GnRH) as an imaging probe, providing an insight into the design of new GnRH peptides for prostate cancer in the future.

Radiofluorination of a NHC-PF5 adduct: toward new probes for 18F PET imaging.

The radiofluorination of N-heterocyclic carbene (NHC) phosphorus(v) fluoride adducts has been investigated. The results show that the IMe-PF5 derivative (IMe = 1,3-dimethylimidazol-2-ylidene) undergoes a Lewis acid promoted 18F-19F isotopic exchange. The resulting radiofluorinated probe is remarkably resistant to hydrolysis both in vitro as well as in vivo.

Pharmacokinetics, absorption, and excretion of radiolabeled revexepride: a Phase I clinical trial using a microtracer and accelerator mass spectrometry-based approach.

PURPOSE: Gastroesophageal reflux disease involves the reflux of gastric and/or duodenal content into the esophagus. Prokinetic therapies, such as the selective 5-hydroxytryptamine receptor 4 agonist revexepride, may aid gastric emptying. This Phase I study evaluated the pharmacokinetics and excretion pathways of [14C]revexepride in healthy individuals using a microtracer approach with accelerator mass spectrometry. PARTICIPANTS AND METHODS: Six healthy men received a single oral dose of 2 mg [14C]revexepride containing ~200 nCi of radioactivity; blood, urine, and fecal samples were collected over a 10-day period. RESULTS: Almost 100% of 14C was recovered: 38.2%±10.3% (mean ± standard deviation) was recovered in urine, and 57.3%±0.4% was recovered in feces. Blood cell uptake was low, based on the blood plasma total radioactivity ratio of 0.8. The mean revexepride renal clearance was 8.6 L/h, which was slightly higher than the typical glomerular filtration rate in healthy individuals. Time to reach maximal concentration was 1.75±1.17 hours (mean ± standard deviation). No safety signals were identified. CONCLUSION: This study demonstrated that revexepride had rapid and moderate-to-good oral absorption. Excretion of radioactivity was completed with significant amounts in feces and urine. Renal clearance slightly exceeded the typical glomerular filtration rate, suggesting the involvement of active transportation in the renal tubules.

Variability in the amount of fluorine-18 fluorodeoxyglucose excreted in urine measured from oncology patients during PET/computed tomography imaging.

The objectives of this work were to estimate the amount of fluorine-18 fluorodeoxyglucose (F-FDG) excreted (AFE) in the patient urine during the uptake phase as percentage of the injected activity and to examine the effect of blood glucose levels (BGL) on the excreted amount and whether it varies among men and women using statistical analysis methods. Radiation dose rates were measured at 1 m from 50 patients, 24 men and 26 women, before and after the first void using a calibrated ionization chamber. The F-FDG was injected in the patients using a calibrated automatic dose injection system. Statistical analysis using hypothesis testing was carried out. Patients with BGL above 5 mmol/l had a higher AFE of 12.3% in comparison with 8.3% of the patients with BGL below 5 mmol/l. A statistically nonsignificant correlation (r=0.183, P<0.249) between AFE and BGL was found; a nonsignificant difference was found in the AFE measured among the male and female patients. The AFE measured was 12±6%, with a range of (2-30%). There was a wide variation in the first void time of 39±8 min, with a range of (17-68) min. A simple noninvasive measurement method is presented that enabled the estimation of the amount of F-FDG excreted from the patient during voiding. Statistical analysis concluded that the amount of F-FDG excreted does not depend on sex, but is perhaps influenced by BGL.

A Mimic of Intra-abdominal Malignancy: Physiological Urinary Excretion of FDG in the Rare Adult Vesicourachal Diverticulum.

Urachal remnant anomalies are rare, and vesicourachal diverticulum is the most uncommon subtype of these anomalies. We present such a rare case of vesicourachal diverticulum that is incidentally discovered during the staging surveillance of a known esophageal cancer with F-FDG PET/CT. The physiological urinary excretion of radiopharmaceutical in the vesicourachal diverticulum mimics intra-abdominal malignancy, which resolves spontaneously in the follow-up FDG PET/CT.

Internal dosimetry for intake of 18FDG using spot urine sample.

In nuclear medicine, workers handle unsealed radioactive materials. Among the materials, (18)FDG is the most widely used in PET/CT technique. Because of the short half-life of (18)F, it is very challenging to monitor internal exposure of nuclear medicine workers using in vitro bioassay. Thus, the authors developed the new in vitro bioassay methodology for short half-life nuclides. In the methodology, spot urine sample is directly used without normalisation to 1-d urine sample and the spot urinary excretion function was newly proposed. In order to estimate the intake and committed dose for workers dealing (18)FDG, biokinetic models for FDG was also developed. Using the new methodology and biokinetic model, the in vitro bioassay for workers dealing (18)FDG was successfully performed. The authors expect that this methodology will be very useful for internal monitoring of workers who deal short-lived radionuclides in the all field as well as the nuclear medicine field.

Compare serum creatinine versus Renal 99mTc-DTPA scan determined glomerular filtration rates in veterans with traumatic spinal cord injury and meurogenic bladder.

OBJECTIVE: This observational study: (a) compared serum creatinine (estimated glomerular filtration rate (EGFR)) to renal isotope 99mTc-DTPA (GFR) determined glomerular filtration rate, and evaluated whether either method (b) better determined the state of renal function, and (c) predict urinary tract infection (UTI), renal and urological structural lesions or mortality in veterans with traumatic spinal cord injury (SCI) and neurogenic bladder (NGB). DESIGN: Observational study. SETTING: VA Medical Center affiliated with Oklahoma University. PARTICIPANTS: Veterans with SCI and regularly followed in SCI clinic. Demographic and clinical data, as well as, EGFR, GFR, blood urea nitrogen (BUN) and serum creatinine levels, and presence of UTI, renal and urinary bladder lesions on renal nuclear scan, renal ultrasound, and cystoscopy studies were recorded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Urological lesions, UTI, and Mortality. RESULTS: For 161 patients with SCI and NGB the mean ± SD for EGFR was 104 ± 36 and 84 ± 32 for GFR. EGFR and GFR were positively correlated (r = 0.34, P = 0.015). GFR was significantly (P < 0.05) more sensitive and specific in determining renal functional state. Neither measures were significant indicator for UTI, renal or urological lesions; GFR was a significant predictor of risk of death (1.2 times increase in risk per 10 unit drop in GFR) even after adjusting for age (P = 0.040). CONCLUSION: While GFR and EGFR are comparable measures of glomerular filtration, GFR was a more informative measure of renal functional state and risk of mortality than EGFR. Neither method predicted the presence of UTI related renal or urological lesions.

Scintigraphic assessment of renal function in steel plant workers occupationally exposed to lead.

OBJECTIVES: Occupational exposure to lead may produce kidney damage, but existing data on the dose range associated with nephrotoxicity are inconclusive. We here assessed renal function under conditions of low to moderate lead exposure using renal scintigraphy. METHODS: Fifty-three male foundrymen (exposed group) and fourty male office workers (control group) from a steel plant were included in the study. Glomerular and tubular renal function were assessed by means of (99m)Tc-DTPA and (99m)Tc-EC clearance, respectively. Urinary markers of glomerular dysfunction (albumin) and tubular damage (α1-microglobulin (α1M), ß2-microglobulin (ß2M), retinol-binding protein (RBP), N-acetyl-ß-glucosaminidase (NAG) activity) were determined using latex beads tests or colorimetry. The lead concentration in blood was measured with atomic absorption spectrometry. RESULTS: The blood lead concentrations were 145.8 (121.3-175.3) and 39.3 (35.1-44.1) µg/l (geometric mean, 95(th) CI, p<0.001) in the exposed and control groups, respectively. Subjects exposed to lead presented with increased (99m)Tc-DTPA clearance (158.3 (148.4-168.8) vs. 135.9 (127.9-144.4) ml/min; p<0.01) and urinary albumin excretion (7.61 (6.28-9.22) vs. 4.78 (4.05-5.65) mg/g creatinine; p<0.001). (99m)Tc-EC clearance and excretion of α1M, ß2M, RBP and NAG were not significantly different between the groups. Significant correlations between (99m)Tc-DTPA clearance and blood lead concentrations (r=0.45; p<0.01) and between urinary albumin excretion and blood lead concentrations (r=0.71; p<0.001) were noted. CONCLUSIONS: Use of renal scintigraphy in present study revealed measurable alterations of renal function under the conditions of low-level lead exposure and suggest that increased glomerular filtration may be an early indicator of kidney damage in subjects occupationally exposed to lead.