RESUMEN
PURPOSE: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. METHODS: 169Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. RESULTS: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. CONCLUSIONS: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers.
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Braquiterapia , Iterbio , Animales , Braquiterapia/métodos , Ratones , Iterbio/química , Distribución Tisular , Nanopartículas/química , Marcaje Isotópico , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Ratones Endogámicos C57BL , Goma Arábiga/química , Femenino , Glicoproteínas/química , Línea Celular Tumoral , Radioisótopos/química , Radioisótopos/uso terapéuticoRESUMEN
We present a four-component relativistic unitary coupled cluster method for atoms and molecules. We have used commutator-based non-perturbative approximation using the "Bernoulli expansion" to derive an approximation to the relativistic unitary coupled cluster method. The performance of the full quadratic unitary coupled-cluster singles and doubles method (qUCCSD), as well as a perturbative approximation variant (UCC3), has been reported for both energies and properties. It can be seen that both methods give results comparable to those of the standard relativistic coupled cluster method. The qUCCSD method shows better agreement with experimental results due to the better inclusion of relaxation effects. The relativistic UCC3 and qUCCSD methods can simulate the spin-forbidden transition with easy access to transition properties. A natural spinor-based scheme to reduce the computational cost of relativistic UCC3 and qUCCSD methods has been discussed.
RESUMEN
Folate receptors (FRs) are known to be over-expressed in several human malignancies and therefore serve as an important target for small radiolabeled folate derivatives for non-invasive imaging of tumor, which is an important tool for future treatment recourse. In the present article, we report the synthesis of a new 99mTc-labeled radiotracer for the aforementioned application following the well-established 99mTc-'4+1' chemistry. Formation of the desired [99mTc]Tc-complex with >95% radiochemical purity was confirmed by radio-HPLC and its structure was ascertained by characterizing a natural rhenium analogue of the said complex. Although the ligand exhibited a weaker affinity towards FRs compared to native folic acid (IC50 8.09 µM vs 29.46 nM), the 99mTc-labeled complex was found to bind folate receptor-positive KB cells with high specificity (â¼90%). Similar studies in a folate receptor negative cell line viz. A549 further corroborated the receptor-specificity of the synthesized complex. In vivo studies in KB tumor xenograft showed moderate uptake of â¼2.6% upto 3 h post-injection with high specificity (â¼80%). The favorable features observed warrant further screening of the current design towards achieving an improved molecular probe for the said application.
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Ácido Fólico , Neoplasias , Humanos , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Radiofármacos , Proteínas Portadoras/metabolismo , Tecnecio/químicaRESUMEN
This overview describes the basic characteristics and chemistry, production and the clinical applications and use of radiopharmaceuticals pertaining to radiosynoviorthesis (RSO). In each of the case scenarios, the physical and clinical parameters that serve as determinants and govern the choice of a particular radionuclide employed for RSO are discussed. References have been drawn on the fundamentals of RSO where applicable, including a brief review of the principles and mechanism of action, the indication and efficacy of RSO in different disease conditions and suggestions set out by the current guideline recommendations.
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Radioisótopos , Radiofármacos , Humanos , Radiofármacos/uso terapéutico , Radioisótopos/uso terapéuticoRESUMEN
The freshwater aquifers of the Indo-Gangetic plains support rich biodiversity which is under the threat of arsenic contamination. The filter feeding bivalve mollusc Lamellidens marginalis is a sessile and sentinel resident of these freshwater habitats. In the present study, the classical cell behaviours of adhesion and aggregation were monitored in the circulating haemocytes of the freshwater bivalve under the exposure of sodium arsenite (NaAsO2) at sublethal concentrations in controlled laboratory conditions for a maximum time-span of sixteen days. The toxic metalloid significantly inhibited non-self adhesion, inter-haemocyte interactions and haemocyte aggregation in a dose and time dependent manner. The natural occurrence of the filopods on the haemocytes was significantly diminished in the bivalves exposed to the inorganic arsenite. Moreover, a significant fall in the kinetics of phagocytosis index and haemocyte adhesion was observed under the in vitro exposure to NaAsO2. Compromised non-self adhesion, cell-cell aggregation and phagocytosis of non-self particles by the bivalve haemocytes probably indicate susceptible immunological status of the bivalve. Such vulnerable immunity of the bivalve probably signifies the nature of imminent threat to the freshwater ecosystem as a whole under inorganic arsenite exposure. The findings would be helpful to design bivalve haemocyte based inexpensive biomonitoring tool to assess the health of freshwater ecosystem under potential arsenic threat.
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Arsénico/toxicidad , Bivalvos/citología , Adhesión Celular/fisiología , Agregación Celular/fisiología , Hemocitos/fisiología , Fagocitosis/fisiología , Animales , Arseniatos/toxicidad , Contaminantes Químicos del Agua/toxicidadRESUMEN
Owing to its favorable radioactive decay characteristics (T1/2 = 32.51 d, Eß [max] = 434.6 keV [70.5%] and 580.0 keV [29.5%], Eγ = 145.4 keV [48.5%]), 141 Ce could be envisaged as a theranostic radionuclide for use in nuclear medicine. The present article reports synthesis and evaluation of 141 Ce complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid (DOTMP) as a potent theranostic agent targeting metastatic skeletal lesions. Ce-141 was produced with 314 ± 29 MBq/mg (n = 6) specific activity and >99.9% radionuclidic purity (n = 6). Around 185 MBq dose of [141 Ce]Ce-DOTMP was synthesized with 98.6 ± 0.5% (n = 4) radiochemical yield under optimized conditions of reaction, and the preparation showed adequately high in vitro stability. Biodistribution studies in normal Wistar rats demonstrated significant skeletal localization and retention of injected activity (2.73 ± 0.28% and 2.63 ± 0.22% of injected activity per gram in femur at 3 hours and 14 days post-injection, respectively) with rapid clearance from non-target organs. The results of biodistribution studies were corroborated by serial scintigraphic imaging studies. These results demonstrate the potential utility of 141 Ce-DOTMP as a theranostic molecule for personalized patient care of cancer patients suffering from painful metastatic skeletal lesions.
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Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Dolor en Cáncer/diagnóstico por imagen , Dolor en Cáncer/radioterapia , Radioisótopos de Cerio/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Adsorción , Animales , Dolor en Cáncer/etiología , Durapatita/química , Marcaje Isotópico , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacocinética , Cintigrafía , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Radiolabeled Arg-Gly-Asp (RGD) peptide derivatives have immense potential for non-invasive monitoring of malignancies overexpressing integrin αv ß3 receptors. Easy availability of suitable radiotracers would augment the utility of this class of molecular imaging agents. Towards this, the present article describes the development of an improved lyophilized kit for the routine clinical formulation of [99m Tc]Tc complex of HYNIC-conjugated dimeric cyclic RGD peptide derivative E-[c(RGDfK)]2 (E = glutamic acid, f = phenyl alanine, K = lysine) without using Sn2+ and systematic evaluation of its efficacy. Five batches of the kits were prepared, and [99m Tc]Tc-HYNIC-E[c(RGDfK)]2 radiotracer was synthesized with high radiochemical purity (98.6 ± 0.5%) and specific activity (124.8 GBq/µmol) using the kits. Biodistribution studies in C57BL/6 mice bearing melanoma tumor exhibited significant accumulation of the radiotracer in tumor (5.32 ± 0.56 %ID/g at 60 min p.i.), and this uptake was also found to be receptor-specific by blocking studies. Preliminary human clinical investigations carried out in 10 breast cancer patients revealed high radiotracer uptake in the tumor along with good tumor-to-background contrast. The developed kit formulation showed an exceptionally high shelf-life of at least 18 months. These results demonstrated promising attributes of the developed kit formulation and warrant more extensive clinical investigations.
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Neoplasias de la Mama/diagnóstico por imagen , Hidrazinas/química , Ácidos Nicotínicos/química , Compuestos de Organotecnecio/química , Compuestos de Organotecnecio/síntesis química , Péptidos Cíclicos/química , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Animales , Técnicas de Química Sintética , Femenino , Semivida , Humanos , Melanoma/diagnóstico por imagen , Melanoma/metabolismo , Ratones , Persona de Mediana Edad , Compuestos de Organotecnecio/farmacocinética , Radioquímica , Distribución TisularRESUMEN
Since the inception of radiation synovectomy, a host of radioactive colloids and microparticles incorporating suitable therapeutic radionuclides have been proposed for the treatment of arthritis. The present article reports the synthesis and evaluation of barium titanate microparticles as an innovative and effective carrier platform for lanthanide radionuclides in the preparation of therapeutic agents for treatment of arthritis. The material was synthesized by mechanochemical route and characterized by X-ray diffraction, scanning electron microscopy, surface area, and particle size distribution analyses. Loading of lanthanide radionuclides (166 Ho, 153 Sm, 177 Lu, and 169 Er) on the microparticles was achieved in high yield (> 95%) resulting in the formulation of loaded particulates with excellent radiochemical purities (> 99%). Radiolanthanide-loaded microparticles exhibited excellent in vitro stability in human serum. In vitro diethylene triamine pentaacetic acid challenge study indicated fairly strong chemical association of lanthanides with barium titanate microparticles. Long-term biodistribution studies carried out after administration of 177 Lu-loaded microparticles into one of the knee joints of normal Wistar rats revealed near-complete retention of the formulation (> 96% of the administered radioactivity) within the joint cavity even 14 days post-administration. The excellent localization of the loaded microparticles was further confirmed by sequential whole-body radio-luminescence imaging studies carried out using 166 Ho-loaded microparticles.
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Artritis/radioterapia , Compuestos de Bario/química , Portadores de Fármacos/química , Elementos de la Serie de los Lantanoides/química , Elementos de la Serie de los Lantanoides/uso terapéutico , Microesferas , Titanio/química , Animales , Compuestos de Bario/farmacocinética , Fenómenos Químicos , Portadores de Fármacos/farmacocinética , Estabilidad de Medicamentos , Radioquímica , Radioisótopos , Ratas , Ratas Wistar , Distribución Tisular , Titanio/farmacocinéticaRESUMEN
Use of bone-seeking radiopharmaceuticals is an established modality in the palliative care of pain due to skeletal metastases. 177 Lu-DOTMP is a promising radiopharmaceutical for this application owing to the ideally suited decay properties of 177 Lu and excellent thermodynamic stability and kinetic rigidity of the macrocyclic complex. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of clinical doses of 177 Lu-DOTMP at hospital radiopharmacy. After extensive radiochemical studies, an optimized strategy for formulation of clinical doses of 177 Lu-DOTMP was developed, which involves simple mixing of approximately 3.7 GBq of 177 Lu activity as 177 LuCl3 solution to an aqueous solution containing 5 mg of DOTMP and 8 mg of NaHCO3 . The proposed protocol yielded 177 Lu-DOTMP with >98% radiochemical purity, and the resultant formulation showed excellent in vitro stability and desired pharmacokinetic properties in animal model. Preliminary clinical investigations in 5 patients showed specific skeletal accumulation with preferential localization in the osteoblastic lesion sites and almost no uptake in soft tissue or any other major nontarget organ. The developed "mix-and-use" strategy would be useful for large number of nuclear medicine centers having access to 177 Lu activity and would thereby accelerate the clinical translation of 177 Lu-DOTMP.
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Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Dolor en Cáncer/complicaciones , Dolor en Cáncer/radioterapia , Lutecio/uso terapéutico , Compuestos Organofosforados/química , Compuestos Organofosforados/uso terapéutico , Radioisótopos/uso terapéutico , Animales , Durapatita/metabolismo , Humanos , Masculino , Compuestos Organofosforados/farmacocinética , Servicio de Farmacia en Hospital , Ratas , Distribución TisularRESUMEN
Positron emission tomography (PET) imaging has transformed diagnostic nuclear medicine and become an essential strategy in cancer management. With the expected growth of this molecular imaging modality, there is a recognized need for new PET probes to address the clinical challenges in the early diagnosis and staging of various types of cancers. In this endeavor, the prospect of using 64Cu in the form of simple Cu2+ ions as PET probe is not only a cost-effective proposition but also seems poised to broaden the palette of molecular imaging probes in the foreseeable future. The usefulness of 64Cu2+ ions as PET probe is based on the fact that Cu is an essential element that plays an important role in cell proliferation and angiogenesis. Over the past few years, there has been continuous flow of evidences based on studies in animal models on the uptake of 64Cu2+ ions in different types of tumors, including, hepatoma, colorectal cancer, prostate cancer, lung cancer, breast cancer, head and neck cancer, fibrosarcoma, melanoma, glioblastoma, and ovarian cancer. The widespread preclinical success of 64Cu2+ ions as PET probe has recently resulted in translation of this radiotracer to clinical settings for noninvasive imaging and staging of prostate cancer in human patients. In this concise review, we have focused on the latest developments in PET imaging of cancer in preclinical and clinical settings using 64Cu2+ ion as a probe and discussed the challenges and opportunities for future development.
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Radioisótopos de Cobre/análisis , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico por imagen , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Melanoma/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
The present study is aimed at carrying out a comparative performance evaluation of different types of (68)Ge/(68)Ga generators to identify the best choice for use in (68)Ga-radiopharmacy. Over the 1 year period of evaluation, the elution yields from the CeO2-based and SiO2-based (68)Ge/(68) Ga generators remained almost consistent, in contrast to the sharp decrease observed in the elution yields from TiO2 and SnO2-based generators. The level of (68)Ge impurity in (68)Ga eluates from the CeO2 and SiO2-based (68)Ge/(68)Ga generator was always <10(-3)%, while this level increased from 10(-3)% to 10(-1)% in case of TiO2 and SnO2-based generators. The level of chemical impurities in (68)Ga eluates from CeO2 and SiO2-based (68)Ge/(68)Ga generators was negligibly low (<0.1 ppm) in contrast to the significantly higher level (1-20 ppm) of such impurities in eluates from other two generators. As demonstrated by radiolabeling studies carried out using DOTA-coupled dimeric cyclic RGD peptide derivative (DOTA-RGD2), CeO2-PAN and SiO2-based generators are directly amenable for radiopharmaceutical preparation, whereas the other generators can be only used after post-elution purification of (68)Ga eluates. Clinically relevant dose of (68)Ga-DOTA-RGD2 was prepared in a hospital radiopharmacy for non-invasive visualization of tumors in breast cancer patients using positron emission tomography.
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Radioisótopos de Galio/química , Generadores de Radionúclidos/instrumentación , Radiofármacos/química , Generadores de Radionúclidos/normasRESUMEN
Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',Nâ³,Nâ³-pentaacetic acid (CHX-Aâ³-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-Aâ³-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-Aâ³-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-Aâ³-DTPA-Cetuximab and (177) Lu-CHX-Aâ³-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-Aâ³-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation.
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Cetuximab/química , Inmunoconjugados/química , Lutecio/química , Radioisótopos de Itrio/química , Animales , Línea Celular Tumoral , Composición de Medicamentos , Inmunoconjugados/farmacocinética , Marcaje Isotópico , Ratones , Imagen Molecular , Tomografía de Emisión de Positrones , Radioquímica , Distribución TisularRESUMEN
Targeted radionuclide therapy using (177) Lu-labeled peptidomimetic inhibitor of prostate specific membrane antigen (PSMA) viz. PSMA-617 is emerging as one the most effective strategies for management of metastatic prostate cancer, which is one of the leading causes of cancer related death. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of therapeutic dose of (177) Lu-PSMA-617 at hospital radiopharmacy using moderate specific activity (177) Lu available at an affordable cost. Extensive radiochemical studies were performed to optimize the required [PSMA-617] / [Lu] ratio and other parameters to formulate 7.4 GBq dose of (177) Lu-PSMA-617. Based on these, 7.4 GBq therapeutic dose of (177) Lu-PSMA-617 was formulated by incubating 160 µg of PSMA-617 with indigenously produced (177) LuCl3 (555 GBq/µg specific activity of (177) Lu) at 90 °C for 30 min. The radiochemical purity of the formulation was 98.3 ± 0.6% (n = 7) which was retained to the extent of >95% after 7 d in normal saline at room temperature and >96% after 2 d in human serum at 37 °C. Preliminary clinical studies showed specific targeting of the agent in the lesion sites and similar physiological distribution as in diagnostic (68) Ga-PSMA-11 PET scans performed earlier. The developed optimized protocol for formulating therapeutic dose of (177) Lu-PSMA-617 could be useful for large number of nuclear medicine therapy clinics across the world having access to moderate specific activity (177) Lu at an affordable cost.
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Dipéptidos/metabolismo , Dipéptidos/uso terapéutico , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Compuestos Heterocíclicos con 1 Anillo/metabolismo , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Lutecio/uso terapéutico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Radioisótopos , Anciano , Antígenos de Superficie/metabolismo , Dipéptidos/química , Dipéptidos/farmacología , Estabilidad de Medicamentos , Glutamato Carboxipeptidasa II/metabolismo , Compuestos Heterocíclicos con 1 Anillo/química , Compuestos Heterocíclicos con 1 Anillo/farmacología , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Control de Calidad , RadioquímicaRESUMEN
Manganese (Mn) is an essential heavy metal that is naturally found in the environment. Daily intake through dietary sources provides the necessary amount required for several key physiological processes, including antioxidant defense, energy metabolism, immune function and others. However, overexposure from environmental sources can result in a condition known as manganism that features symptomatology similar to Parkinson's disease (PD). This disorder presents with debilitating motor and cognitive deficits that arise from a neurodegenerative process. In order to maintain a balance between its essentiality and neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels. These include transporters involved in Mn uptake, and newly discovered Mn efflux mechanisms. This review will focus on current studies related to mechanisms underlying Mn import and export, primarily the Mn transporters, and their function and roles in Mn-induced neurotoxicity. Though and essential metal, overexposure to manganese may result in neurodegenerative disease analogous to Parkinson's disease. Manganese homeostasis is tightly regulated by transporters, including transmembrane importers (divalent metal transporter 1, transferrin and its receptor, zinc transporters ZIP8 and Zip14, dopamine transporter, calcium channels, choline transporters and citrate transporters) and exporters (ferroportin and SLC30A10), as well as the intracellular trafficking proteins (SPCA1 and ATP12A2). A manganese-specific sensor, GPP130, has been identified, which affords means for monitoring intracellular levels of this metal.
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Homeostasis/fisiología , Intoxicación por Manganeso/metabolismo , Manganeso/metabolismo , Animales , Humanos , Manganeso/toxicidad , Intoxicación por Manganeso/diagnóstico , Intoxicación por Manganeso/etiología , Proteínas de Transporte de Membrana/metabolismo , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Transporte de Proteínas/fisiologíaRESUMEN
This paper describes a systematic comparative evaluation of five commonly used bifunctional chelators, namely,p-isothiocyanato benzyl derivatives of diethylenetriaminepentacetic acid (DTPA-NCS), trans-cyclohexyl diethylenetriaminepentaceticacid (CHX-Aâ³-DTPA-NCS), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NCS), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS), and 3,6,9,15-tetraazabicyclo [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA-NCS), on the basis of their ability to complex 90Y at room temperature, in vitro and in vivo stability and clearance pattern in biological system. The results of the experiments carried out revealed that CHX-Aâ³-DTPA-NCS was the most promising option as it could be radiolabeled with 90Y at room temperature with highest specific activity and demonstrated high in vitro stability in human serum and in presence of challenging metal ions commonly present inhuman plasma. The clearance pattern in Swiss mice revealed that 90Y-CHX- Aâ³-DTPA-NCS cleared through the kidneys with minimum retention in any other major organ. Thus, the use of cyclohexyl-DTPA based bifunctional chelators would increase the scope of making 90Y-labeled agents suitable for targeted therapy.
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Quelantes/química , Quelantes/farmacocinética , Radiofármacos/química , Radiofármacos/farmacocinética , Radioisótopos de Itrio/química , Acetatos/química , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Humanos , Ratones , Ácido Pentético/análogos & derivados , Ácido Pentético/químicaRESUMEN
While radiation synovectomy (RSV) constitutes a successful paradigm for the treatment of arthritis, a major cornerstone of its success resides in the selection of appropriate radiolabeled agent. Among the radionuclide used for RSV, the scope of using (177)Lu [T1/2 = 6.65 d, Eß(max) = 497 keV, Eγ = 113 KeV (6.4%), 208 KeV (11%)] seemed to be attractive owing to its suitable decay characteristics, easy availability, and cost-effective production route. The present article describes a formulation of (177)Lu-labeled hydroxyapatite (HA) using ready-to-use kits of HA particles of 1-10 µm size range. The developed kits enable convenient one-step preparation of (177)Lu-HA (400 ± 30 MBq doses) in high radiochemical purity (>99%) and stability at hospital radiopharmacy. The preparation showed promising results in pre-clinical studies carried out in Wistar rats bearing arthritis in knee joints. In preliminary clinical investigation, significant improvement in the disease conditions was reported in 10 patients with rheumatoid arthritis of knee joints treated with 333 ± 46 MBq doses of (177)Lu-HA. The studies reveal that while (177)Lu labeled HA particles holds considerable promise as a cost-effective agent for RSV, the adopted strategy of using HA kits could be a potential step toward wider clinical utilization of radiolanthanide-labeled HA particles.
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Artritis Reumatoide/diagnóstico por imagen , Hidroxiapatitas/farmacocinética , Lutecio/farmacocinética , Radiofármacos/farmacocinética , Adulto , Animales , Femenino , Humanos , Hidroxiapatitas/administración & dosificación , Hidroxiapatitas/síntesis química , Hidroxiapatitas/uso terapéutico , Marcaje Isotópico , Articulación de la Rodilla/diagnóstico por imagen , Lutecio/uso terapéutico , Masculino , Persona de Mediana Edad , Radioisótopos/farmacocinética , Radioisótopos/uso terapéutico , Radiofármacos/administración & dosificación , Radiofármacos/síntesis química , Radiofármacos/uso terapéutico , Ratas , Ratas Wistar , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Altered copper metabolism in cancer has been linked to increased intracellular copper uptake mediated by human copper transporter 1, with [64Cu]Cu2+ as a potential biomarker for cancer theranostics. [64Cu]CuCl2 PET-CT though explored in various malignancies, a lack of standardized protocol exists, particularly regarding fasting status before imaging. This analysis aimed to evaluate the requirement of fasting for [64Cu]CuCl2 PET-CT along with temporal changes in physiological organ uptake in delayed scans. A total of 26 patients of prostate carcinoma who underwent [64Cu]CuCl2 PET-CT imaging were divided into two groups: (1) nonfasting (nâ =â 12) and (2) fasting (nâ =â 14). The nonfasting group received an average dose of 350â MBq, while the fasting group received 300â MBq of [64Cu]CuCl2, and PET-CT images acquired approximately 60-90â min (1â h image) and 3-3.5â h (delayed image) after intravenous injection of the tracer. An experienced nuclear medicine physician evaluated the images for qualitative assessment between the groups. Multiple spherical regions of interest were placed at sites of physiological organ uptake of the tracer and over the diseased lesions to measure the mean SUVmax. No significant difference was observed in the qualitative assessment of the images between the two groups (except for a slight predilection towards more hepatic tracer retention observed in the fasting group), including in the delayed images. The liver demonstrated the highest tracer uptake in all patients, with a mean SUVmax of 21.5 in the fasting group and 19.7 in the nonfasting group, showing no significant difference (Pâ =â 0.32). The kidneys, intestines, and salivary glands also showed similar trends of tracer uptake in both groups. The study illustrated that the fasting or nonfasting status did not affect image quality or semiquantitative measurements significantly in physiological organs and diseased lesions in patients with carcinoma prostate.
RESUMEN
OBJECTIVE: This study aimed to explore 64-Copper-Chloride ( 64 CuCl 2 ) PET-CT in various malignancies and demonstrate a head-to-head comparison of uptake on 64 CuCl 2 PET/computed tomography (CT) and 18 fluorodeoxyglucose ( 18 FDG)-PET/CT scans for different malignancies, with an emphasis on 18 FDG nonavid malignancies. METHODS: Fifty-three patients diagnosed with various biopsy-proven malignancies (except prostate cancer) were recruited in this prospective study. All the patients underwent both 64 CuCl 2 PET/CT and 18 FDG-PET/CT. 64 CuCl 2 PET/CT was acquired at 1, 3 and 24 h time points. We studied the physiological biodistribution of 64 CuCl 2 in the various organs, corroborated the uptake of 64 CuCl 2 with various types of malignancies and comparison of their uptake with 18 FDG-PET/CT and their correlation with each other in various lesions. RESULTS: The biodistribution study showed that the liver concentrated 64 CuCl 2 the most out of all the organs, followed by the pancreas and large intestine. Liver and intestinal activity increased subsequently with delayed imaging, and the washout of 64 CuCl 2 was noted in the pancreas in delayed images and followed a hepatobiliary excretion of tracer over a period of time. In lesion-wise analysis, it was noted that the primary neuroendocrine tumor, melanoma and renal/urothelial malignancy group showed more uptake of 64 CuCl 2 , than that in metastasis and vice-versa was noted in lung and soft tissue malignancies. Comparing it with 18 FDG, it was seen that FDG showed more uptake in lesions and showed no significant correlation (Kappa value: 0.089) with the uptake of 64 CuCl 2 in the lesion-wise comparison. CONCLUSION: 64 CuCl 2 PET/CT did not show any added advantage over 18 FDG-PET/CT in the evaluation of the studied malignancies, both primary and their metastasis. Biodistribution studies showed the liver as the organ with maximum uptake, which implies it may hinder the detection of abdominal or hepatic involvement of the disease.