Radiopharmaceutical Research Research Articles

Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): An Emerging Tool in Radiopharmaceutical Science.

Although radioactive experiments are necessary in radiopharmaceutical drug discovery and theranostic cancer research, they are expensive, require special facilities, and face certain restrictions. Thus, finding techniques not involving radioactivity is highly beneficial for minimizing these disadvantages in such research. In this regard, methods using inductively coupled plasma-mass spectrometry (ICP-MS) have emerged as viable alternatives to traditional radioactive approaches. Despite its potential, practical applications of ICP-MS in radiopharmaceutical cancer research have only emerged in recent years. This Perspective focuses on the development and implementation of nonradioactive ICP-MS-based assays in radiopharmaceutical research and aims to inspire future research efforts in this area.

Ultrasound-Assisted Solid-Phase Affibody Synthesis Using ZEGFR:1907 as an Example-Superior to the Conventional Protocol?

Affibody molecules represent a class of highly specific binders of particular interest for the development of highly affine target-specific radiopharmaceuticals. Their chemical synthesis is, however, intricate due to their considerable length of 58 amino acids; thus, approaches to optimize their preparation are constantly being sought. As ultrasound assistance has recently been shown to increase the efficiency of amino acid conjugation during solid-phase peptide synthesis (SPPS), the influence of ultrasonication on the outcome of the SPPS-based preparation of the EGFR-specific affibody ZEGFR:1907 was compared to a common protocol relying on mechanical shaking. After the identification of a suitable solid support for the study, the execution of the systematic comparison of both approaches showed that conventional and ultrasound-assisted syntheses yielded equivalent results with analogous composition of the raw products. Further, both approaches produced the affibody in good isolated yields of >20% when applying the same optimal reagent excesses and coupling times for the conjugation of each amino acid. This indicates that, under optimal reaction conditions, the choice of solid support used has a much stronger influence on the outcome of the preparation of ZEGFR:1907 than the application of ultrasound, which did not further improve the synthesis results. Therefore, for the chemical synthesis of affibodies, great attention should be paid to the choice of a suitable solid support, enabling this highly interesting class of biomolecules to be obtained in good yields and to bring them more into the focus of radiopharmaceutical research.

Design and Construction of a Radiochemistry Laboratory and cGMP-Compliant Radiopharmacy Facility.

The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment.

Reactive Palladium-Ligand Complexes for 11C-Carbonylation at Ambient Pressure: A Breakthrough in Carbon-11 Chemistry.

The Pd-Xantphos-mediated 11C-carbonylation protocol (also known as the "Xantphos- method"), due to its simplistic and convenient nature, has facilitated researchers in meeting a longstanding need for preparing 11C-carbonyl-labeled radiopharmaceuticals at ambient pressure for positron emission tomography (PET) imaging and drug discovery. This development could be viewed as a breakthrough in carbon-11 chemistry, as evidenced by the rapid global adoption of the method by the pharmaceutical industry and academic laboratories worldwide. The method has been fully automated for the good manufacturing practice (GMP)-compliant production of novel radiopharmaceuticals for human use, and it has been adapted for "in-loop" reactions and microwave technology; an impressive number of 11C-labeled compounds (>100) have been synthesized. Given the simplicity and efficiency of the method, as well as the abundance of carbonyl groups in bioactive drug molecules, we expect that this methodology will be even more widely adopted in future PET radiopharmaceutical research and drug development.

The Chemistry of Phenylimidotechnetium(V) Complexes with Isocyanides: Steric and Electronic Factors

Organometallic approaches are of ongoing interest for the development of novel functional 99mTc radiopharmaceuticals, while the basic organotechnetium chemistry seems frequently to be little explored. Thus, structural and reactivity studies with the long-lived isotope 99Tc are of permanent interest as the foundation for further progress in the related radiopharmaceutical research with this artificial element. Particularly the knowledge about the organometallic chemistry of high-valent technetium compounds is scarcely developed. Here, phenylimido complexes of technetium(V) with different isocyanides are introduced. They have been synthesized by ligand-exchange procedures starting from [Tc(NPh)Cl3(PPh3)2]. Different reactivity patterns and products have been obtained depending on the steric and electronic properties of the individual ligands. This involves the formation of 1:1 and 1:2 exchange products of Tc(V) with the general formulae [Tc(NPh)Cl3(PPh3)(isocyanide)], cis- or trans-[Tc(NPh)Cl3(isocyanide)2], but also the reduction in the metal and the formation of cationic technetium(I) complex of the formula [Tc(isocyanide)6]+ when p-fluorophenyl isocyanide is used. The products have been studied by single-crystal X-ray diffraction and spectroscopic methods, including IR and multinuclear NMR spectroscopy. DFT calculations on the different isocyanides allow the prediction of their reactivity towards electron-rich and electron-deficient metal centers by means of the empirical SADAP parameter, which has been derived from the potential energy surface of the electron density on their potentially coordinating carbon atoms.

Photonuclear Alchemy: Obtaining Medical Isotopes of Gold from Mercury Irradiated on Electron Accelerators.

In our work, the photonuclear production of 198,199Au isotopes for nuclear medicine purposes was studied, and a method for their recovery from irradiated mercury was developed. The yields of the corresponding nuclear reactions were determined, and a comparison of various methods of obtaining gold radioisotopes was provided. New sorbents based on benzo-15-crown-5, which selectively binds gold, were studied, and the optimal conditions for Au recovery with a high degree of purification from mercury were found. It was established that, for the fast and quantitative recovery of Au isotopes, it was necessary to add at least 0.1 mg of the carrier. As a result, the developed method can be regularly used to obtain 198,199Au for the research of radiopharmaceuticals based on them.

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer—Regulatory Process, Part II: The Role of the Institutional Review Board in Food and Drug Administration–Regulated Radiopharmaceutical Research

<b>CE credit:</b> For CE credit, you can access the test for this article, as well as additional <i>JNMT</i> CE tests, online at https://www.snmmilearningcenter.org. Complete the test online no later than June 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test. The goal of clinical research is to advance medical knowledge in hopes of improving patient care. At the core of clinical research is the need to perform research on human volunteers. This is absolutely required for the eventual approval of drugs and certain therapies. Unfortunately, history is replete with stories involving exploitation and abuse of individuals in research. Clinical research using radiopharmaceuticals introduces additional apprehension. Although the past few decades have witnessed significant improvements in safety and ethics, there remain indelible images seared into the psyche of the general population. Those new to clinical research may find themselves asking questions such as, What are the ethical guidelines and regulations for clinical research, How are they enforced and by whom, and How do we ensure the safety of participants? The answer, in large part, is the oversight and actions of the institutional review board. This article will focus on familiarizing the reader with the institutional review board and its role in protecting the rights and welfare of humans participating as subjects in Food and Drug Administration–regulated radiopharmaceutical research.

Squaric Acid Bisphposphonates for Theranostics of Bone Metastasis - the Easy DOTA-Zoledronate.

Bisphosponates are an interesting molecular class and in recent years their application has found its way into radiopharmaceutical research and thus into molecular imaging. In addition to great imaging of bone metastases, bisphospnate-based tracers for imaging also have some significant drawbacks. For example, their synthesis is often difficult. Additionally, this can lead to complex and almost impossible purification and quality control. This has limited the production and labeling of suitable molecular and their widespread use to a few facilities. Our squaric acid-based approach provides a way to overcome these problems and makes the synthesis as well as the purification of the compounds much easier. In addition, we were able to demonstrate that labeling with 68Ga is possible under the typical conditions.

Synthesis and biological evaluation of a &amp;lt;sup&amp;gt;99m&amp;lt;/sup&amp;gt;Tc-labeled glucose derivative for tumor imaging

<p indent="0mm">The development of novel tumor-imaging agents for single-photon-emission-computed tomography (SPECT) with good performance, simple preparation and low price is a hot topic in the field of radiopharmaceutical research. ^99mTc is the most widely used SPECT nuclide in clinic. In order to develop a novel ^99mTc-labeled tumor radiopharmaceuticals, in this study, a glucose derivative (CN6DG) containing isonitriles was synthesized and it was radiolabeled with ^99mTc to obtain the ^99mTc-CN6DG complex with high radiochemical purity (&gt;95%). The complex is hydrophilic (log<italic>D</italic>=−2.52±0.33) and has good stability <italic>in vitro </italic>and<italic> in vivo</italic>. <italic>In vitro</italic> cell-uptake assay showed that tumor cells uptake of the complex was related to glucose transporters. In S180 tumor-bearing mice <sc>2 h</sc> after injection, the tumor-uptake value was 0.75±0.12 %ID/g and the tumor/muscle, tumor/blood ratios were 4.41 and 18.75, respectively. In A549 tumor-bearing mice after <sc>2 h</sc> of post-injection, the tumor-uptake value was 2.62±0.23 %ID/g, which was higher than that of ^99mTc-CN5DG (1.48±0.23 %ID/g). Its tumor/blood (52.4 <italic>vs</italic>. 49.33) ratios and tumor/muscle ratios (6.89 <italic>vs</italic>. 24.67) were as good as that of ^99mTc-CN5DG. The SPECT/CT imaging results in S180 and A549 tumor-bearing mice showed that it had significant tumor uptakes, indicating that it is a promising tumor-imaging agent.

Current use and future potential of (physiologically based) pharmacokinetic modelling of radiopharmaceuticals: a review.

Rationale: Physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PK) modelling approaches are widely accepted in non-radiopharmaceutical drug development and research, while there is no major role for these approaches in radiopharmaceutical development yet. In this review, a literature search was performed to specify different research purposes and questions that have previously been answered using both PBPK and population PK modelling for radiopharmaceuticals. Methods: The literature search was performed using the databases PubMed and Embase. Wide search terms included radiopharmaceutical, tracer, radioactivity, physiologically based pharmacokinetic model, PBPK, population pharmacokinetic model and nonlinear mixed-effects model. Results: Eight articles and twenty articles were included for this review based on this literature search for population PK modelling and PBPK modelling, respectively. Included population PK analyses showed to have an added value to develop predictive models for a population and to describe individual variability sources. Main purposes of PBPK models appeared related to optimizing treatment (planning), or more specifically: to find the optimal combination of peptide amount and radioactivity, to optimize treatment planning by reducing the number of measurements, to individualize treatment, to get insights in differences between pre-therapeutic and therapeutic scans or to understand inter-patient differences. Other main research subjects were regarding radiopharmaceutical comparisons, selecting ligands based on their peptide characteristics and gaining a better understanding of drug-drug interactions. Conclusions: The use of PK modelling approaches in radiopharmaceutical research remains scarce, but can be expanded to obtain a better understanding of PK and whole-body distribution of radiopharmaceuticals in general. PK modelling of radiopharmaceuticals has great potential for the nearby future and could contribute to the evolving research of radiopharmaceuticals.

Current status and future perspective of radiopharmaceuticals in China.

Radiopharmaceuticals are essential components of nuclear medicine and serve as one of the cornerstones of molecular imaging and precision medicine. They provide new means and approaches for early diagnosis and treatment of diseases. After decades of development and hard efforts, a relatively matured radiopharmaceutical production and management system has been established in China with high-quality facilities. This review provides an overview of the current status of radiopharmaceuticals on production and distribution, clinical application, and regulatory supervision and also describes some important advances in research and development and clinical translation of radiopharmaceuticals in the past 10 years. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00259-021-05615-6.

Common Shortcomings in Study on Radiopharmaceutical Design Research: A Case Study of 99mTc-Labelled Methotrexate

The aim of the work carried out was to draw attention to shortcomings that often appear at the stage of designing new radiopharmaceuticals. Based on a case study of 99mTc-labelled methotrexate, this article describes frequent mistakes or misconceptions present not only in the referenced studies, but also in numerous radiopharmaceutical studies. The recommendations provided in this article highlight fundamental aspects of the credibility of radiopharmaceutical scientific research leading to the reliable results.

Has COVID-19 Ushered in a New Normal for Medical Meetings?

[...]the question arises: are virtual and hybrid meetings the new normal? We don't yet have a new normal and we aren't yet meeting in person, says Alan Packard, PhD, president of Society of Nuclear Medicine and Molecular Imaging (SNMMI) director of the Radiopharmaceutical Research Laboratory at Boston Children's Hospital, and associate professor of radiology at Harvard Medical School. After the success of the National Basketball Association playoffs, which were played in a bubble at Walt Disney World in Orlando, FL, Wilson was encouraged that live meetings could still be held during the pandemic with the right safety precautions in place. World Class CME held its National Diagnostic Imaging Symposium in December 2020 at Disney's Yacht Club Resort for a much smaller than usual live audience, with most faculty participating remotely. According to Dr Packard, feedback on the 2020 virtual SNMMI Annual Meeting was positive.

A Review of Molecular Imaging of Glutamate Receptors.

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.

Hybrid Imaging Agents for Pretargeting Applications Based on Fusarinine C-Proof of Concept.

Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imaging agents were used for pretargeting applications utilizing click reactions with a trans-cyclooctene (TCO) tagged targeting vector for a proof of principle both in vitro and in vivo. Starting from FSC, the fluorophores Sulfocyanine-5, Sulfocyanine-7, or IRDye800CW were conjugated, followed by introduction of one or two Tz motifs, resulting in mono and dimeric Tz conjugates. Evaluation included fluorescence microscopy, binding studies, logD, protein binding, in vivo biodistribution, µPET (micro-positron emission tomography), and optical imaging (OI) studies. 68Ga-labeled conjugates showed suitable hydrophilicity, high stability, and specific targeting properties towards Rituximab-TCO pre-treated CD20 expressing Raji cells. Biodistribution studies showed fast clearance and low accumulation in non-targeted organs for both SulfoCy5- and IRDye800CW-conjugates. In an alendronate-TCO based bone targeting model the dimeric IRDye800CW-conjugate resulted in specific targeting using PET and OI, superior to the monomer. This proof of concept study showed that the preparation of FSC-Tz hybrid imaging agents for pretargeting applications is feasible, making such compounds suitable for hybrid imaging applications.

A Small Field, High Resolution γ-Camera System dedicated to SPECT Imaging

A small field, high resolution γ-Camera system dedicated to radiopharmaceutical research and other clinical SPECT (Single Photon Emission Computed Tomography) applications is currently being developed in our group. The system is equipped with the 3” HAMAMATSU R2486 Position Sensitive PhotoMultiplier Tube (PSPMT) with a 16X+16Y-crossed wire anode and various pixelated and ho- mogeneous scintillation crystals. Planar images are created from the recorded charge signals by applying the resistive chain technique. The main part of this work focuses on the development of new correction methods for the improvement of the spatial resolution and the uniformity of the γ-Camera. The spatial distortion correction technique is based on lookup tables with the coordinates of reference points which are selected during the calibration phase of the system for a given set of collimator and scintillation crystal. The applied algorithm incorporates 2D-interpolation tech- niques and has been developed on a full automated graphics environment making use of the HIGZ (High Level Interface to Graphics and ZEBRA) program libraries from CERN. Both correction methods for the spatial distortion and non-uniformity have been applied to phantom images using several combinations of small capillaries filled with water solution of 99mTc. Comparative studies are shown on planar im- ages for different phantom geometries. The method is also extended to tomographic images and the obtained SPECT improvement in resolution is discussed.

Multivariate optimization and validation of a procedure to direct determine acetonitrile and ethanol in radiopharmaceuticals by GC-FID

A fast and simplified analytical procedure was developed and validated for the direct determination of organic solvents (acetonitrile and ethanol) in radiopharmaceuticals samples ([18F]FMISO, [18F]FES and [18F]FLT) by gas chromatography coupled with flame ionization detection (GC-FID). Optimization studies were performed with the aid of two-level full factorial design. The optimum conditions were located using Derringer's desirability function. Procedure validation assured the compliance of the assay to Brazilian regulatory agencies standards (ANVISA and INMETRO). Values for LOD and LOQ were commensurate with the level at which the impurities must be controlled. Good linearity was achieved (R ≥ 0.990) for acetonitrile and ethanol concentrations ranging from 0.003 to 0.09% (w/v) and 2.1 to 11.0% (v/v), respectively. Accuracy and precision assessments were performed using samples fortified with standards (spiked samples). The developed procedure proved to be selective, sensitive, accurate (95.9–117.8% of nominal values) and precise (RSD ≤ 9.7%). The validated procedure was successfully used to assess organic solvents levels in a Brazilian radiopharmaceuticals samples manufactured by Radiopharmaceutical Research and Production Unit of Nuclear Technology Development Center (CDTN), in Belo Horizonte (Brazil). The analytes could be well resolved in 1.5 min and accurately determined in three different types of radiopharmaceuticals. This procedure is applicable to samples even with high ethanol content up to 11% (v/v). Other advantages include no sample preparation, short chromatographic separation time and minimum manual operation. As results, the proposed procedure can be useful in the routine analysis for the determination of acetonitrile and ethanol in radiopharmaceutical samples.

Radiochemical and analytical aspects of inter-institutional quality control measurements on radiopharmaceuticals

BackgroundClinically applied radiopharmaceuticals have to meet quality release criteria like a high radiochemical yield and radiochemical purity. Many radiopharmaceuticals do not have marketing authorization and have no dedicated monograph within the European pharmacopeia, therefore general monographs on quality control have to be applied for clinical applications. These criteria require standardization and validation in labeling and preparation, including QC measurements according to well-defined standard operation procedures. QC measurements however, are often based on detection techniques specific for a certain LC-system. Multi-institutional research and development of new radiopharmaceuticals lead to an increase in multicenter trials. Although all institutes’ radiopharmacies are using the same standardized labeling and operation procedures, they often use different LC and radiodetection systems. Here we present a comparison of QC assessments for 3 radiopharmaceuticals with focus on the interpretation of chromatograms, data-output and potential differences in local practical performances of QC on (U)HPLC.MethodsQC assessments for [111In]In-CCK, [68Ga]Ga-Bombesin and [177Lu]Lu-PSMA analogs were compared. Two of the radiopharmaceutical QC assessments were also applied in other institutes using their own HPLC-systems and concordant software. Data from the HPLC-injections and measurements is processed and summarized in chromatograms, based on a variety of smoothing algorithms for which different software programs are applied. Described radiopeptides were labeled and analyzed according their standardized labeling and operation procedures.ResultsIntegration of main peaks on chromatograms resulted in a range of RCP, depending on the smoothing algorithm used. [111In]In-CCK(A), 68Ga-Bombesin(B) and [177Lu]Lu-PSMA(C) analogs had a RCP range of 88%–96%(A), 89–95%(B) and 92–99%(C) respectively. Important factors affecting final RCP value were site specific background radiation-levels, intrinsic system properties such as noise and sensitivity, personal interpretation e.g. peak-tailing and smoothing algorithms.ConclusionMeasurement of RCP shows a strong method- and system-dependency, even when parameters are validated, standardized and SOP are followed. Release criteria are frequently based on RCP data from one central location. The lack of inter inter institutional validation and standardization in RCP determination makes the results therefore rather arbitrary. For multicenter trials, we recommend to compare locally determined RCP under validated and standardized conditions of in-line activity detection between institutes for each radiopharmaceutical.

Introduction of radiopharmaceutical administration policy of FDA

Radiopharmaceuticals have been widely used in the diagnosis, treatment and monitoring of diseases, and they play an important role in new drug development. Food and Drug Administration(FDA) has rich experience in the administration of radiopharmaceuticals. This article mainly interprets the regulatory policy of FDA for radiopharmaceuticals from the aspects of definition, regulations and registration, trying to provide reference for domestic research of radiopharmaceuticals. Key words: Radiopharmaceuticals; United States Food and Drug Administration; Drug and narcotic control; Trends

A 89Zr-labeled lipoplex nanosystem for image-guided gene delivery: design, evaluation of stability and in vivo behavior.

BackgroundWith the advances in radiopharmaceutical research, the development of image-guided therapy has become a major interest. While the development of theranostic nanotherapeutics is frequently associated with cancer chemotherapy, phototherapy and radiotherapy, there is little information available on the in vivo monitoring of gene delivery systems and the application of image-guided approach in gene therapy. The goal of this work was to determine the in vivo behavior of DNA delivery nanosystems - based on cationic gemini surfactants – designed for image-guided gene therapy. We tested the feasibility of monitoring tumor accumulation of gene delivery nanoparticles by positron emission tomography.MethodsTo be able to conjugate radiotracers to the nanoparticles, a deferoxamine-modified gemini surfactant was synthesized, DNA-containing lipoplex nanoparticles were formulated, and radiolabeled with Zirconium-89 (89Zr). The pharmacokinetics and biodistribution of 89Zr labeled surfactant and 89Zr labeled nanoparticles were monitored in mice by microPET/CT imaging and ex vivo gamma counting.ResultsModification of the nanoparticles with deferoxamine did not alter their physicochemical properties. The radiolabeled nanoparticles (labeling efficiency of 95±3%) were stable in PBS and serum. The biological half-life of the 89Zr labeled nanoparticles was significantly higher compared to 89Zr labeled surfactant. As expected, the nanoparticles had significantly higher liver accumulation than the radiolabeled surfactant alone and lower kidney accumulation. Tumor uptake was detected at 2 hours post injection and decreased throughout the 3-day monitoring.ConclusionWe propose that radiolabeling DNA delivery lipoplex nanosystems is a promising approach for the design and optimization of image-guided nanomedicines, especially in the context of cancer gene therapy.