55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

doi:10.1016/S0969-8051(99)00077-3

Nuclear Medicine and Biology

Volume 27, Issue 1, January 2000, Pages 77-81

https://doi.org/10.1016/S0969-8051(99)00077-3 Get rights and content

Abstract

The feasibility of imaging renal function with ⁵⁵Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with ⁵⁵Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time–activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of ⁵⁵Co-EDTA were compared with those for ⁵¹Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time–activity curves showed that ⁵⁵Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of ⁵⁵Co-EDTA and ⁵¹Cr-EDTA in blood were not significantly different, showing that the nature of the M⁺⁺ has no influence on the in vivo behavior of EDTA. ⁵⁵Co can be produced easily by cyclotron irradiation and ⁵⁵Co-EDTA is a promising physiological tracer for nephrological research using PET.

Introduction

Medical imaging continues to grow in importance and positron emission tomography (PET) is the most specific and sensitive technique for quantitatively imaging molecular pathways and molecular interactions within organs and tissues. PET is used routinely in oncology, cardiology, and neurology.

Absolute quantification by PET of any functional process depends on the availability of specific radiopharmaceuticals and on an appropriate tracer kinetic model, requiring an in-depth understanding of the metabolic fate of the labeled compound.

The purpose of this study was to search for a suitable radiotracer to study renal function using PET. The kidney is an organ characterized by both high metabolic activity and a high regional blood flow distribution.

In clinical practice, glomerular filtration rate (GFR), the most important parameter for evaluation and monitoring the renal function, can be directly estimated by measuring creatinine and inulin clearance.

Giese and Rossing (6) and Blaufox et al. (1) showed that total plasma clearances of ⁵¹Cr-ethylene diamine tetraacetic acid (EDTA) and conventional inulin clearance yield very similar results. For the EDTA total plasma clearance method 3, 5 to be effective, a number of plasma samples need to be measured, because the nuclear characteristics of ⁵¹Cr are not suitable for single photon emission computed tomography (SPECT) studies.

We investigated the application of dynamic PET using ⁵⁵Co-EDTA as radiotracer for renal imaging in Wistar rats. This paper reports on the biodistribution in normal Wistar rats and in one animal with reduced left kidney function; blood and urinary clearance of ⁵⁵Co-EDTA compared with ⁵¹Cr-EDTA; and the influence of the liver activity on the right kidney data.

Section snippets

Synthesis

⁵⁵Co is a positron emitter ( t_1/2=17.53 h; E_β+max=1.50 MeV [46%], 1.02 MeV [26%], and 1.11 MeV [4%]); E_γ=931 (75%) and 477 keV (20%) produced by proton irradiation ( energy interval=23–18 MeV, intensity=3–5 μA, duration=2 h) of an iron foil ( thickness=325 μm, diameter=15 mm, purity=99.99+%) and separated by solvent extraction with isopropyl ether. The target consisted of natural high purity iron (Goodfellow Metals Ltd., Cambridge, UK), with a low concentration of Co (4 μg/g). The purification

Synthesis

About 5–8 mCi (185–300 MBq) of ⁵⁵Co-EDTA with a nonradioactive carrier of less than 1 μg was produced routinely. Based on nuclear data (excitation functions, threshold energy, interfering reactions), radionuclidic contamination of ⁵⁶Co ( t_1/2=77.3 d, E_β=1.46 MeV, E_γ=847 and 1237 keV) could be reduced to less than 2% of the total activity at the end of production. Quality control with GC-FID on a Porapack®Q-column as stationary phase showed that the organic solvent concentration (isopropyl

Discussion

It is clear that PET, traditionally used in oncological, cardiological, and neurological studies, has the possibility to focus on any organ and tissue, for example, liver (8) and kidneys (9). PET studies with tracers such as ¹³NH₃ and ¹¹C-acetate, used mainly in cardiology, have been evaluated successfully for quantification of renal blood flow (4) and imaging in renal diseases (13). Because those tracers, besides their participation in a high number of different biochemical processes, are

Acknowledgements

The authors highly appreciate the assistance of M. Van Landschoot, T. Dheuvaert, J. Sambre, and J. Keppens. We thankfully acknowledge the financial support of the Fund for Scientific Research–Flanders (FWO-Vl) and the University Research Fund.

References (13)

E.S. Garnett et al.
Measurement of glomerular filtration rate in man using Cr51 edetic acid complexes
Lancet
(1967)
D. Killion et al.
Positron emission tomographyA new method for determination of renal function
J. Urol.
(1993)
M.C. Lagunas-Solar et al.
Cyclotron production of carrier-free cobalt-55, a new positron-emitting label for bleomycin
Int. J. Appl. Radiat. Isot.
(1979)
H. Sharma et al.
Production of cobalt-55, a short-lived, positron emitting radiolabel for Bleomycin
Appl. Radiat. Isot.
(1986)
Blaufox M. D., Aurell M. A., Bubeck B., Fommei E. F., Piepsz A., Russell C., Taylor A., Thomsen H. S., Volterrani D....
Buxton D. B., Schwaiger M., Nguyen A., Phelps M. E., Schelbert H. R. (1988) Radiolabeled acetate as a tracer of...

There are more references available in the full text version of this article.

Cited by (48)

Production cross sections of radionuclides in the proton induced reactions on natural iron with the proton energy of 57 MeV
2024, Nuclear Engineering and Technology
The production cross sections of ^55,56,57Co, ^52gFe, ^52g,54Mn, ⁵¹Cr, and ⁴⁸V from the ^natFe (p,x) reactions were measured using a proton energy of 57 MeV at the Korea Multi-purpose Accelerator Complex (KOMAC) in Gyeongju, Korea. The conventional stacked-foil activation method and offline γ-ray spectroscopy were used to determine the excitation functions of proton induced nuclear reactions on iron. The measured excitation functions were compared with experimental data in literature and theoretical data from the TENDL-2021 library. The present data show generally good agreement with other experimental data, but discrepancies were found between the present data and the excitation functions of the TENDL-2021 library in the investigated energy range, except for ^56,57Co and ⁵⁴Mn.
Folate-based radiotracers for nuclear imaging and radionuclide therapy
2022, Coordination Chemistry Reviews
Folate receptor α (FRα) is overexpressed on numerous tumorous cell types such as ovarian or endometrial cancer cells. Moreover, FRα is absent from most healthy tissues as it is normally expressed only on the surface of proximal tubules cells of kidneys and choroid plexus. Thus, folate-based radiopharmaceuticals have emerged this last two decades as FRα is a target of choice to diagnose and treat numerous cancers. Nuclear imaging is a performing diagnostic technology using highly sensitive detectors and specific radiopharmaceuticals used to detect tumors at an earlier stage. Herein, an overview of the development of folate-based radiopharmaceuticals to detect FRα-positive tumors by nuclear imaging using positron emission tomography (PET) and single photon emission computed tomography (SPECT) is exposed. Strategies developed to improve precursor synthesis, bioavailability, clearance, and affinity to FRα will be detailed. Advances made to decrease kidney uptake open the gate to targeted radionuclide therapy (TRT) using folate-based radiopharmaceuticals to treat FRα-positive tumors. Thus, radiofolates used in TRT and more precisely in a theranostic approach will be depicted in this review.
Measurements of production cross-sections of medical radioisotopes (57Ni, 55,57,58Co, 54Mn, 51Cr) and other by-products (56Ni, 56Co, 56Mn) from the 59Co(p,x) reactions
2020, Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
Citation Excerpt :
A few applications for the 57,58Co and 57Ni isotopes are described in Refs. [3,4], where the production of these radionuclides from the natCu(p,x) and natCu(α,x) reactions is investigated. The short-lived 55Co (T1/2 = 17.53 h) has many medical applications due to its decay characteristics and is considered promising for imaging renal functions using positron emission tomography (PET) [5]. 51Cr-release assays are employed for tumor cytolysis and the quantification of cytotoxicity [6].
We studied the excitation functions of ⁵⁹Co(p,x) reactions and measured the production cross-sections of medical radioisotopes (⁵⁷Ni, ^55,57,58Co, ⁵⁴Mn, ⁵¹Cr) and other by-products (⁵⁶Ni, ⁵⁶Co, ⁵⁶Mn) from their threshold to a proton energy of 43.7 MeV. The stacked-foil activation method was employed to irradiate the samples with an external beam from the MC-50 cyclotron at the Korea Institute of Radiological and Medical Sciences (KIRAMS), Korea. Off-line γ-ray spectrometry was used to measure the activities of the produced radionuclides. The integral yields for the thick target of the investigated radionuclides were also calculated from the measured excitation functions. The measured results were compared with the literature data as well as with theoretical values obtained from the TENDL-2017 library based on the TALYS-1.9 code.
Radionuclide candidates for β+γ coincidence PET: An overview
2020, Applied Radiation and Isotopes
Following the advancement of the Positron Emission Tomography (PET), a novel technique emerged which takes advantage of the gamma quanta emitted, in some cases, after the β+ decay. While ^44gSc is commonly agreed the best choice to validate this new modality, other radioisotopes must also be considered in the future. We present them in this paper, along with their possible applications, properties and the optimal production routes with the use of the accelerators.
Cyclotron production and radiochemical separation of 55Co and 58mCo from 54Fe, 58Ni and 57Fe targets
2017, Applied Radiation and Isotopes
Citation Excerpt :
A more promising approach for the use of this radiometal is by binding it to a chelator and potentially conjugating this complex to a targeting vector. So far, only seven studies have followed this chelator-based approach (Dam et al., 2016; Garousi et al., 2017; Goethals et al., 2000; Mastren et al., 2015; Srivastava et al., 1994; Thisgaard et al., 2011b; Wallberg et al., 2010). Goethals et al. (Goethals et al., 2000) labeled 55Co to ethylene diamine tetraacetic acid (EDTA) and characterized this complex for the application in the measurement of the glomerular filtration rate in kidneys via PET, a study which is commonly performed with the perfusion tracer 51Cr-EDTA (Chantler et al., 1969).
This work presents the production with a cyclotron of the positron emitter ⁵⁵Co via the ⁵⁴Fe(d,n) and ⁵⁸Ni(p,α) reactions and the Auger electron emitter ^58mCo via the ⁵⁷Fe(d,n) reaction after high current (40 μA p and 60 μA d) irradiation on electroplated targets. High specific activity radionuclides (up to 55.6 GBq/μmol ⁵⁵Co and 31.8 GBq/μmol ^58mCo) with high radionuclidic purity (99.995% ⁵⁵Co from ⁵⁴Fe, 98.8% ⁵⁵Co from ⁵⁸Ni, and 98.7% ^58mCo from ⁵⁷Fe at end of bombardment, EoB), in high activity concentration (final separated radionuclide in < 0.6 mL) and with almost quantitative overall activity separation yield (> 92%) were obtained after processing of the irradiated targets with novel radiochemical separation methods based on HCl dissolution and the resin N,N,N′,N′-tetrakis-2-ethylhexyldiglycolamide (DGA, branched). One hour long irradiations using 38–65, 110–214 and 59–78 mg of enriched ⁵⁴Fe (99.93%), ⁵⁸Ni (99.48%) and ⁵⁷Fe (95.06%), respectively, electroplated over a 1.0 cm² surface, yielded 58² ± 66 MBq ⁵⁵Co, 372 ± 14 MBq ⁵⁵Co and 810 ± 186 MBq ^58mCo, respectively, decay corrected to EoB. The separation methods allow for the recovery of the costly enriched target materials, which were reconstituted into metallic targets after novel electroplating methods, with an overall recycling efficiency of 93 ± 4% for iron. The produced radionuclides were used to radiolabel the angiogenesis marker antibody TRC105 conjugated to the chelator NOTA as a demonstration of their quality.
Evaluated cross-sections of 55Co radionuclide, a non-standard positron emitter for clinical applications
2017, Radiation Physics and Chemistry
Citation Excerpt :
prepared for quantitation of cerebrospinal fluid (CSF) kinetics in different areas of the brain using positron emission tomography. The radionuclides are prepared by for quantitation of cerebrospinal fluid (CSF) kinetics in different areas of the brain using positron emission tomograph 55Co radioisotope was also applied as a potential renal imaging agent thru dynamic PET imaging of renal function of animal by Goethals et al. (2000). There are three common routes for the production of 55Co, namely 56Fe(p,2n)55Co, 54Fe(d,n)55Co and 58Ni(p,α)55Co.
Production cross-sections of Cobalt-55 (T_1/2=17.53 h, $E_{β^{+}}^{mean} =$ 570 keV, $I_{β^{+}}^{total} =$ 76%), a non-standard positron emitter have been evaluated in the energy range of 40 MeV down to the threshold energy of the ⁵⁶Fe(p,2n)⁵⁵Co nuclear reaction due to its significance as a potential PET imaging agent in medical applications. Experimental cross-sections of ⁵⁵Co radionuclide that lies within the scope of this work were collected from the EXFOR database, and renormalized using the latest agreed values of decay data and monitor cross-sections. Simultaneous Evaluation on KALMAN (SOK) code combined with least-squares method was applied to the corrected cross-sections to obtain evaluated cross-sections together with the covariance information. Knowledge of the underlying uncertainties in evaluated nuclear data, i.e., covariances are useful to improve the accuracy of nuclear data.

View all citing articles on Scopus

View full text

Article preview

Nuclear Medicine and Biology

Abstract

Introduction

Section snippets

Synthesis

Synthesis

Discussion

Acknowledgements

References (13)

Measurement of glomerular filtration rate in man using Cr51 edetic acid complexes

Lancet

Positron emission tomographyA new method for determination of renal function

J. Urol.

Cyclotron production of carrier-free cobalt-55, a new positron-emitting label for bleomycin

Int. J. Appl. Radiat. Isot.

Production of cobalt-55, a short-lived, positron emitting radiolabel for Bleomycin

Appl. Radiat. Isot.

Cited by (48)

Production cross sections of radionuclides in the proton induced reactions on natural iron with the proton energy of 57 MeV

Folate-based radiotracers for nuclear imaging and radionuclide therapy

Measurements of production cross-sections of medical radioisotopes (<sup>57</sup>Ni, <sup>55,57,58</sup>Co, <sup>54</sup>Mn, <sup>51</sup>Cr) and other by-products (<sup>56</sup>Ni, <sup>56</sup>Co, <sup>56</sup>Mn) from the <sup>59</sup>Co(p,x) reactions

Radionuclide candidates for β+γ coincidence PET: An overview

Cyclotron production and radiochemical separation of <sup>55</sup>Co and <sup>58m</sup>Co from <sup>54</sup>Fe, <sup>58</sup>Ni and <sup>57</sup>Fe targets

Evaluated cross-sections of <sup>55</sup>Co radionuclide, a non-standard positron emitter for clinical applications

Original Articles55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

Abstract

Introduction

Section snippets

Synthesis

Synthesis

Discussion

Acknowledgements

Lancet

J. Urol.

Int. J. Appl. Radiat. Isot.

Appl. Radiat. Isot.

Original Articles
⁵⁵Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study