Application In Radionuclide Therapy Research Articles

The application of radionuclide therapy for breast cancer

Radionuclide-mediated diagnosis and therapy have emerged as effective and low-risk approaches to treating breast cancer. Compared to traditional anatomic imaging techniques, diagnostic radionuclide-based molecular imaging systems exhibit much greater sensitivity and ability to precisely illustrate the biodistribution and metabolic processes from a functional perspective in breast cancer; this transitions diagnosis from an invasive visualization to a noninvasive visualization, potentially ensuring earlier diagnosis and on-time treatment. Radionuclide therapy is a newly developed modality for the treatment of breast cancer in which radionuclides are delivered to tumors and/or tumor-associated targets either directly or using delivery vehicles. Radionuclide therapy has been proven to be eminently effective and to exhibit low toxicity in eliminating both primary tumors and metastases, and even undetected tumors. In addition, the specific interaction between the surface modules of the delivery vehicles and the targets on the surface of tumor cells enables radionuclide targeting therapy, and this represents an exceptional potential for this treatment in breast cancer. This article reviews the development of radionuclide molecular imaging techniques that are currently employed for early breast cancer diagnosis and both the progress and challenges of radionuclide therapy employed in breast cancer treatment.

Mathematical Simulation in Nuclear Medicine for Optimization Diagnostic Accuracy of SPECT/CT

Purpose: To develop the method of mathematical simulation in the field of nuclear medicine and its
 practical application in research aimed at improving the diagnostic accuracy of the SPECT/CT method.
 The basic principles of the method of mathematical simulation in nuclear medicine and the main modules of the software package “Virtual Platform for Simulation Tests of the SPECT/CT Method”, created
 at the laboratory for simulation in nuclear medicine of Novosibirsk State University and the Institute of
 Theoretical and Applied Mechanics.
 Material and methods: The main principles of the developed software package are the realism of the ‘virtual patient’ mathematical model, the accuracy in modeling of physical processes in visualization, as
 well as simulation conducting close to clinical practice. All studies were carried out in collaboration
 with clinicians. The software complex was verified by comparison with clinical data. Numerical experiments have shown a close correspondence between the results of clinical and virtual studies. In simulation tests, the same errors were obtained on images that were observed on clinical images. Simulation
 computer tests were carried out using the software package “Virtual Platform...” in the field of nuclear
 oncology, cardiology and neurology, aimed at studying the accuracy of images of pathological foci to assess the possibility of switching to quantitative SPECT, as well as optimizing the protocol for examining
 patients.
 Results: Simulation tests have shown that in order to move to quantitative SPECT, it is not enough to be
 limited to the development of a methodology for calibrating SPECT systems for a particular radionuclide. There are problems without understanding and solving which it is impossible to talk about the diagnostic accuracy of the quantitative SPECT method. Such problems are edge artifacts that appear on
 the images of pathological foci, and the rule of stopping the iterative algorithm when the values of activity in the area of interest (pathological focus) that are closest to the true values are reached. A stopping
 criterion based on Pearson's modified chi-square test of goodness of fit is proposed. There is a significantly good correlation between the proposed stop criterion and the minimum RMS error of the image
 reconstruction. The results of simulation modeling with the aim of optimizing SPECT examinations of
 brain perfusion demonstrated the possibility of reducing the data recording time compared to the standard protocol by at least two times.
 Conclusion: The computer simulation method presented in this paper is a practical technology that
 contributes to the optimization and development of a quantitative SPECT method to achieve the best
 possible results in the imaging of pathological foci. Further development of the software package is focused on applications in radionuclide therapy and theranostics.

Recent Innovations and Nano-Delivery of Actinium-225: A Narrative Review.

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted.

Synthesis and Preclinical Evaluation of a Novel FAPI-04 Dimer for Cancer Theranostics.

Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts in a wide variety of tumors enables a highly selective targeting strategy using FAP inhibitors (FAPIs). Quinoline-based FAPIs labeled with radionuclides have been widely developed for tumor-targeted nuclear medicine imaging. However, the short retention time of FAPIs at the tumor site limits their application in radionuclide therapy. In this study, a novel FAPI-04 dimer was synthesized and labeled with radionuclides to prolong the retention time in tumors for imaging and therapy. To prepare the FAPI-04 dimer complex, DOTA-Suc-Lys-(FAPI-04)2, we used Fmoc-Lys(Boc)-OH as the linker to conjugate two FAPI-04 structures by an amide reaction. The resulting product was further modified by DOTA groups to allow for conjugation with radioactive metals. Both [68Ga]Ga-(FAPI-04)2 and [177Lu]Lu-(FAPI-04)2 showed a radiochemical purity of >99% and remained stable in vitro. In vivo, micro-PET images of SKOV3, A431, and H1299 xenografts revealed that the tumor uptake of [68Ga]Ga-(FAPI-04)2 was about twice that of [68Ga]Ga-FAPI-04 and that the accumulation of [68Ga]Ga-(FAPI-04)2 at the tumor site did not significantly decrease even 3h after injection. The tumor-abdomen ratio of [68Ga]Ga-(FAPI-04)2 images was significantly higher than that of [18F]F-FDG images. For radionuclide therapy, [177Lu]Lu-(FAPI-04)2 effectively retarded tumor growth and displayed good tolerance. In conclusion, the DOTA-Suc-Lys-(FAPI-04)2 design enhanced its uptake in FAP-expressing tumors, improved its retention time at the tumor site, and produced high-contrast imaging in xenografts after radionuclide labeling. Furthermore, it showed a noticeable antitumor effect. DOTA-Suc-Lys-(FAPI-04)2 provides a new approach for applying FAPI derivatives in tumor theranostics.

Dosimetry in radionuclide therapy: the clinical role of measuring radiation dose.

Radionuclide therapy is a rapidly expanding oncological treatment method. Overwhelmingly, the application of radionuclide therapy in clinical practice relies on fixed or empirical dosing strategies. In principle, the application of dosimetry promises to improve patient outcomes by tailoring administered radionuclide therapy activities to each patient's unique tumour burden and tumour uptake. However, robust prospective data are scarce due to few prospective randomised clinical trials investigating the use of dosimetry in radionuclide therapy. In this Review, we describe the role of dosimetry as it has been applied historically and in modern clinical practice and its potential future applications. We further emphasise areas of future growth and a potential pathway to optimised personalised activity modulation of radionuclide therapy.

Elucidating the coordination chemistry of the radium ion for targeted alpha therapy.

The coordination chemistry of Ra2+ is poorly defined, hampering efforts to design effective chelators for 223Ra-based targeted alpha therapy. Here, we report the complexation thermodynamics of Ra2+ with the biomedically-relevant chelators DOTA and macropa. Our work reveals the highest affinity chelator to date for Ra2+ and advances our understanding of key factors underlying complex stability and selectivity for this underexplored ion.

Synthesis, Preclinical Evaluation, and a Pilot Clinical PET Imaging Study of 68Ga-Labeled FAPI Dimer

Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including the FAP inhibitors (FAPIs) 04 and 46, have shown promising results in tumor diagnosis. However, these molecules have a relatively short tumor-retention time for peptide-targeted radionuclide therapy applications. We aimed to design a 68Ga-labeled FAPI dimer, 68Ga-DOTA-2P(FAPI)2, to optimize the pharmacokinetics and evaluate whether this form is more effective than its monomeric analogs. Methods:68Ga-DOTA-2P(FAPI)2 was synthesized on the basis of the quinoline-based FAPI variant (FAPI-46), and its binding properties were assayed in CAFs. Preclinical pharmacokinetics were determined in FAP-positive patient-derived xenografts using small-animal PET and biodistribution experiments. The effective dosimetry of 68Ga-DOTA-2P(FAPI)2 was evaluated in 3 healthy volunteers, and PET/CT imaging of 68Ga-FAPI-46 and 68Ga-DOTA-2P(FAPI)2 was performed on 3 cancer patients. Results:68Ga-DOTA-2P(FAPI)2 was stable in phosphate-buffered saline and fetal bovine serum for 4 h. The FAPI dimer showed high affinity and specificity for FAP invitro and invivo. The tumor uptake of 68Ga-DOTA-2P(FAPI)2 was approximately 2-fold stronger than that of 68Ga-FAPI-46 in patient-derived xenografts, whereas healthy organs showed low tracer uptake and fast body clearance. The effective dose of 68Ga-DOTA-2P(FAPI)2 was 1.19E-02 mSv/MBq, calculated using OLINDA. Finally, the PET/CT scans of the 3 cancer patients revealed higher intratumoral uptake of 68Ga-DOTA-2P(FAPI)2 than of 68Ga-FAPI-46 in all tumor lesions (SUVmax, 8.1-39.0 vs. 1.7-24.0, respectively; P < 0.001). Conclusion:68Ga-DOTA-2P(FAPI)2 has increased tumor uptake and retention properties compared with 68Ga-FAPI-46, and it could be a promising tracer for both diagnostic imaging and targeted therapy of malignant tumors with positive expression of FAP.

Pyridine-containing octadentate ligand NE3TA-PY for formation of neutral complex with 177Lu(III) and 90Y(III) for radiopharmaceutical applications: Synthesis, DFT calculation, radiolabeling, and in vitro complex stability

Targeted radionuclide therapy is a developing therapeutic modality for cancer and employs a cytotoxic radionuclide bound to a chelating agent and a bioactive molecule with high binding affinity for a specific biomarker in tumors. An optimal chelator is one of the critical components to control therapeutic efficacy and toxicity of targeted radionuclide therapy. We designed a new octadentate ligand NE3TA-PY (7-[2-[(carboxymethyl)(2-pyridylmethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) for β-particle-emitting 177Lu and 90Y with targeted radionuclide therapy applications. The pyridine-containing polyaminocarboxylate ligand was proposed to form a neutral complex with Lu(III) and Y(III). The new chelator NE3TA-PY was synthesized and experimentally and theorectically studied for complexation with 177Lu(III) and 90Y(III). DFT-optimized structures of Y(III)-NE3TA-PY and Lu(III)-NE3TA-PY complexes were predicted. NE3TA-PY displayed excellent radiolabeling efficiency with both 177Lu and 90Y. The new chelator (NE3TA-PY) bound to 177Lu was more stable in human serum and better tolerated when challenged by EDTA than 90Y-labeled NE3TA-PY. Our findings suggest that the new chelator (NE3TA-PY) produced excellent Lu-177 radiolabeling and in vitro complex stability profiles.

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

The 225Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with 225Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO2 nanoparticles (NPs) as carrier for 225Ac and its decay products. The surface of TiO2 nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P (5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO2-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO2-PEG-SP(5-11) conjugates were labelled with 225Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO2 surface. The labelled bioconjugates almost quantitatively retain 225Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of 221Fr, a first decay daughter of 225Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized 225Ac-TiO2-PEG-SP(5-11) has shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours.

Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods

The main applications of 188Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188Re images.In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object’s true activity. Each object’s activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial -camera were performed to investigate the accuracy of the TEW method.Good quantification accuracy (errors <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods decreased (errors >15%), mostly due to partial-volume effects. The Monte-Carlo simulations confirmed that TEW-scatter correction applied to 188Re, although practical, yields only approximate estimates of the true scatter.

Nanozeolite bioconjugates labeled with 223Ra for targeted alpha therapy

IntroductionAlpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters, 223Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of 223Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite–Substance P bioconjugates as vehicles for 223Ra radionuclides for targeted α therapy. MethodsThe sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5–11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA–silane–PEG–SP(5–11) bioconjugates were labeled with 223Ra by exchange of the Na+ cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested. ResultsThe 223Ra-labeled nanozeolite bioconjugate almost quantitatively retains 223Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized 223RaA–silane–PEG–SP(5–11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro. ConclusionsSubstance P functionalized nanozeolite-A represents a viable solution for the use of the 223Ra in vivo generator as a therapeutic construct for targeting glioma cells.

Synthesis, radiolabelling, and biodistribution studies of triazole derivatives for targeting melanoma

Molecular probes that target specific markers expressed in solid tumours are in demand for cancer imaging and radionuclide therapy applications. The synthesis, characterization, and in vivo evaluation of radioiodinated triazoles designed as probes to target melanoma are described here. Compounds were prepared using a thermal click reaction between ethynylstannane and methyl 2-azidoacetate, resulting in preferential formation of the corresponding 1,4-tin triazole. The primary amine of various targeting vectors was then coupled to the resulting tin triazole methyl ester. These precursors were labelled with no carrier added 123I or 125I and purified by high performance liquid chromatography to give isolated radiochemical yields between 6% and 51% and radiochemical purities of &gt;95% in all cases. Among the evaluated compounds, N-(2-diethylamino-ethyl)-2-(4-iodo-[1,2,3]triazol-1-yl)acetamide (7a) and N-(1-benzylpiperidin-4-yl)-2-(4-iodo-1H-1,2,3-triazol-1-yl)acetamide (7d) showed the most promising in vivo data, and their 123I-labelled forms were used in single photon emission computed tomography computed tomography (SPECT–CT) imaging studies. The imaging data showed excellent tumour visualization with a very high signal to noise ratio.

Silver impregnated nanoparticles of titanium dioxide as carriers for 211At

Abstract The 211At radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately use of 211At is limited, because astatine as the heaviest halogen forms weak bond with carbon atoms in the biomolecules which makes 211At bioconjugates unstable in physiological conditions. In our work we propose a new solution for binding of 211At which consists of using nanoparticles of titanium dioxide modified with silver atoms as carriers for 211At. Ag+ cations have been absorbed on the nanometer-sized TiO2 particles (15 and 32 nm) through ion exchange process and were reduced in Tollens' reaction. The obtained TiO2-Ag nanoparticles were labeled with 211At. It was found that labeling yields were almost quantitative under reducing conditions, while under oxidizing conditions they dropped to about 80%. The labeled nanoparticles exhibited very high stability in physiological salt, PBS buffer, solutions of peptides (0.001 M cysteine, 0.001 M glutathione) and in human blood serum. To make TiO2/Ag nanoparticles well dispersed in water and biocompatible their surface was modified with a silane coupling agent containing poly(ethyleneglycol) molecules. The developed functionalization approach will allow us to attach biomolecules to the TiO2/Ag surface.

Enhanced retention of encapsulated ions in cross-linked polymersomes.

Polymer vesicles (polymersomes) composed of poly(butadiene-b-poly(ethylene oxide)) (PB-b-PEO) are known for their stability and limited permeability. However, when these vesicles are diluted, substances, such as ions, encapsulated in the aqueous cavity can be released due to vesicle disruption. In previous studies, we have shown that these vesicles can be loaded efficiently with sufficient quantities of radionuclides to allow application in radionuclide therapy and pharmacokinetics evaluation, provided that there is no loss of the encapsulated radionuclides when diluted in the bloodstream. In this paper, in order to stabilize the carriers, we propose to cross-link the hydrophobic part of the polymersome membrane and to investigate whether such cross-linking induced by γ radiation can enhance the retention of ions (radionuclides). Retention of ions encapsulated in the lumen in such cross-linked carriers has not been previously quantitatively evaluated, although it is of ultimate importance in any medical application. Here, we also investigate how cross-linking affects the transport of radionuclides (loading) through the membrane of the vesicles. The integrity of the vesicles as a function of the radiation dose is also investigated, including morphological changes. The results show that cross-linking hinders the transport of ions through the membrane, which also leads to higher retention of ions encapsulated prior to cross-linking in the vesicles. Electron micrographs show that the shape of the polymersomes is not greatly affected by γ radiation when left in the original solvent (phosphate buffered saline (PBS) or Milli-Q water), but when diluted in a good solvent for both blocks, i.e., tetrahydrofuran (THF), disintegration of the vesicles and the appearance of droplet-like structures is observed, which had not been reported previously. The results of the present study help to formulate polymersomes as carriers for radionuclide therapy, demonstrating a way to prevent in vivo release of radionuclides, caused by dilution-induced destabilization of the nanocarriers.

The emerging potential of 177Lu-EDTMP: an attractive novel option for radiometabolic therapy of skeletal metastases

Between 60 and 84 % of patients with solid cancers develop bone metastases, the main complication that severely impairs quality of life and performance status and constitutes one of the major challenges of oncological practice. Among other palliative treatments, therapy with bone-seeking radiopharmaceuticals is part of the armamentarium available in the clinical setting to treat bone pain caused by skeletal metastases. Although several radionuclides have been proposed to this purpose, the most widely used radiopharmaceuticals are the b emitters Srchloride and Sm-ethylenediamine-tetra-methylene phosphonate (Sm-EDTMP), while the more recently approved a emitter Ra-chloride plays an increasing role in this scenario. Based on clinical experience acquired for over two decades, Sm-EDTMP has an excellent profile in terms of both efficacy and toxicity, as confirmed by a recent systematic review and meta-analysis of literature on therapy with Sr-chloride and Sm-EDTMP published between 2001 and 2011 [1]. Compared with an overall efficacy for bone palliation of 70 % (either partial or complete) when used as single agents and 74 % when combined with other therapies, the overall toxicity as single agents was 11 %, mostly reversible mild-to-moderate side-effects. Furthermore, interest is growing also on the potential antitumor efficacy of these agents, especially if combined with chemotherapy agents. The market cost of Sm-EDTMP is a drawback limiting a more widespread use of this radiopharmaceutical in low-income countries, thus reviving interest in earlier studies that had explored the potential of Lu as a therapeutic radionuclide to be coupled with EDTMP (US Patent 4898724, 1990. Organic amine phosphonic acid complexes for the treatment of calcific tumors. Wilson DA, Volkert WA, Troutner DE, Goeckeler WF). Lutetium-177 has favorable characteristics such as the low energy b emission, which should reduce toxicity, and a 6.73 day half-life, which is advantageous for the distribution logistics to distant areas. Moreover, the most important feature which makes the production of Lu especially attractive is the very high thermal neutron capture cross-section of the target Lu, through the reaction Lu(n,c)Lu, the highest (r = 2,060 barns) among all (n,c)-produced radionuclides currently used for therapy. Such large cross-section of the reaction ensures that Lu can be produced with adequately high specific activity for radionuclide therapy applications even when using moderate flux reactors, as those that can be employed for medical use even in several low-income countries. It also ensures that there will be no constraints in the large-scale production of Lu and hence the increasing global demand for this radionuclide in the coming years can be met comfortably. In this regard, enriched Lu (with isotopic abundance above 80 %) is relatively inexpensive (200 euros/mg) and available through multiple sources; furthermore, in the long run the cost of Lu should decrease significantly, as more producers will entry into the market. Moreover, Lu can also be produced through thermal neutron irradiation of natural Lu. Preliminary screening of Lu-polyphosphonate complexes suggested that EDTMP has favorable properties to be considered for further investigations. Indeed, biodistribution studies in animals have revealed selective accumulation of Lu-EDTMP in the skeleton (up to *60 % of injected activity) with major renal clearance, while a feasibility clinical study in 10 patients with skeletal S. Mazzarri F. Guidoccio G. Mariani (&) Regional Center of Nuclear Medicine, University of Pisa, Via Roma 57, 56126 Pisa, Italy e-mail: giuliano.mariani@med.unipi.it

Gamma radiation exposure of accompanying persons due to Lu-177 patients

Neuroendocrine tumours (NET) are cancers usually observed and arisen in the stomach, intestine, pancreas and breathing system. Recently, radionuclide therapy applications with Lu-177 peptide compound are rapidly growing; especially effective clinical results are obtained in the treatment of well-differentiated and metastatic NET. In this treatment, Lu-177-DOTA, a beta emitter radioisotope in the radiopharmaceutical form, is given to the patient by intravenous way. Lu-177 has also gamma rays apart from beta rays. Gamma rays have 175 keV average energy and these gamma rays should be under the control in terms of radiation protection. In this study, we measured the exposure dose from the Lu-177 patient.

Editorial Review of 2014

Editorial Review of 2014

Functionalized NaA nanozeolites labeled with 224,225Ra for targeted alpha therapy

The 223Ra, 224Ra, and 225Ra radioisotopes exhibit very attractive nuclear properties for application in radionuclide therapy. Unfortunately the lack of appropriate bifunctional ligand for radium is the reason why these radionuclides have not found application in receptor-targeted therapy. In the present work, the potential usefulness of the NaA nanozeolite as a carrier for radium radionuclides has been studied. 224Ra and 225Ra, α-particle emitting radionuclides, have been absorbed in the nanometer-sized NaA zeolite (30–70 nm) through simple ion exchange. 224,225Ra-nanozeolites exhibited very high stability in solutions containing physiological salt, EDTA, amino acids, and human serum. To make NaA nanozeolite particles dispersed in water their surface was modified with a silane coupling agent containing poly(ethylene glycol) molecules. This functionalization approach let us covalently attach a biomolecule to the NaA nanozeolite surface.

MIRD Pamphlet No. 24: Guidelines for Quantitative 131I SPECT in Dosimetry Applications

The reliability of radiation dose estimates in internal radionuclide therapy is directly related to the accuracy of activity estimates obtained at each imaging time point. The recently published MIRD pamphlet no. 23 provided a general overview of quantitative SPECT imaging for dosimetry. The present document is the first in a series of isotope-specific guidelines that will follow MIRD 23 and focuses on one of the most commonly used therapeutic radionuclides, (131)I. The purpose of this document is to provide guidance on the development of protocols for quantitative (131)I SPECT in radionuclide therapy applications that require regional (normal organs, lesions) and 3-dimensional dosimetry.

Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607

Stability of radiolabelled cholecystokinin 2 (CCK2) receptor targeting peptides has been a major limitation in the use of such radiopharmaceuticals especially for targeted radionuclide therapy applications, e.g. for treatment of medullary thyroid carcinoma (MTC). The purpose of this study was to compare the in vitro stability of a series of peptides binding to the CCK2 receptor [selected as part of the COST Action on Targeted Radionuclide Therapy (BM0607)] and to identify major cleavage sites. Twelve different 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-minigastrin/CCK conjugates were provided within an European COST Action (BM0607) by different laboratories and radiolabelled with (177)Lu. Their in vitro stabilities were tested in fresh human serum. Radiochemical yields (RCY) and intact radioligands for half-life calculations were determined by radio-HPLC. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis of metabolites was performed to identify cleavage products using conjugates labelled with excess stable (nat)Lu, incubated in serum at 37°C. Urine metabolite analysis after injection in normal mice was performed by radio-HPLC analysis. Variable stability in human serum was found for the different peptides with calculated half-lives between 4.5 ± 0.1 h and 198 ± 0.1 h (n = 2). In urine of normal mice only metabolised peptide fragments were detected even at short times after injection for all peptides. MALDI-TOF MS revealed a major cleavage site of all minigastrin derivatives between Asp and Phe-NH(2) at the C-terminal end. Development of CCK2 receptor ligands especially for therapeutic purposes in patients with MTC or small cell lung cancer (SCLC) is still ongoing in different laboratories. This comparative study provided valuable insight into the importance of biological stability especially in the context of other results of this comparative trial within the COST Action BM0607.