177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

Reber, Josefine; Haller, Stephanie; Leamon, Christopher P.; Müller, Cristina

doi:10.1158/1535-7163.mct-13-0422-t

Cited by 20 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biodistribution studies of 177 Lu-EC0800 and 177 Lu-cm09 were performed in KB tumor-bearing nude mice as previously reported [19,22]. In brief, KB cells (5 x 10 6 in 100 µL phosphate buffered saline (PBS)) were inoculated into the subcutis of each shoulder, two weeks before injection of the radiofolates.…”

Section: Biodistribution Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Haller

Reber

Brandt

et al. 2015

Nuclear Medicine and Biology

Self Cite

View full text Add to dashboard Cite

Section: Biodistribution Studiesmentioning

confidence: 99%

“…Biodistribution data of 177 Lu-EC0800 and 177 Lu-cm09 have been previously published by our group [19,22]. Herein, further time points after injection of the radiofolates were investigated in order to refine the dosimetric calculations (Table 2).…”

Section: Biodistribution Of 177 Lu-ec0800 and 177 Lu-cm09 And Dosimetmentioning

confidence: 99%

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Haller

Reber

Brandt

et al. 2015

Nuclear Medicine and Biology

Self Cite

View full text Add to dashboard Cite

“…[4] Among those radionuclides,t he increase in 177 Lu applications has enriched its potential for research and therapeutic procedures and established it at the forefront of clinical radionuclide therapy. [5] Radioisotope 177 Lu has favorably long nuclear decay properties (t 1/2 = 6.65 d) and can be used to easily radiolabel av ariety of molecular carriers. [6] As such, 177 Lu promises to benefit nanoparticle-mediated combination therapy.Previous studies explored 177 Lu-labeled gold nanoparticles for preclinical nuclear medicine.…”

mentioning

confidence: 99%

Efficient Uptake of ¹⁷⁷Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy

et al. 2017

Angew Chem Int Ed

View full text Add to dashboard Cite

The benefits to intracellular drug delivery from nanomedicine have been limited by biological barriers and to some extent by targeting capability.W ei nvestigated as izecontrolled, dual tumor-mitochondria-targeted theranostic nanoplatform (Porphyrin-PEG Nanocomplexes,P PNs). The maximum tumor accumulation (15.6 %ID g À1 ,7 2h p.i.) and ideal tumor-to-muscle ratio (16.6, 72 hp.i.) was achieved using an optimizedP PN particle sizeo fa pproximately 10 nm, as measured by using PET imaging tracing. The stable coordination of PPNs with 177 Lu enables the integration of fluorescence imaging (FL) and photodynamic therapy( PDT) with positron emission tomography (PET) imaging and internal radiotherapy( RT). Furthermore,t he efficient tumor and mitochondrial uptake of 177 Lu-PPNs greatly enhanced the efficacies of RT and/or PDT.T his work developed af acile approach for the fabrication of tumor-targeted multi-modal nanotheranostic agents,w hiche nables precision and radionuclide-based combination tumor therapy.Nanomedicine is renowned for its feasibility and controllability to create all-in-one multi-functional properties for cancer theranostics.[1] Nanoparticle-mediated combinatorial therapeutic regimens are increasingly being used by researchers to improve therapies because of their greater tumor cell killing effects at the targeted site.[2] Specifically,r adiationbased combination therapy has become aclinical standard in curative and palliative treatment regimens.[3] Recently,radionuclide therapy using particle-emitting radioisotopes (for example, 177 Lu, 90 Y, and 131 I) has presented promising results for the palliative treatment of several cancers.[4] Among those radionuclides,t he increase in 177 Lu applications has enriched its potential for research and therapeutic procedures and established it at the forefront of clinical radionuclide therapy.[5] Radioisotope 177 Lu has favorably long nuclear decay properties (t 1/2 = 6.65 d) and can be used to easily radiolabel av ariety of molecular carriers.[6] As such, 177 Lu promises to benefit nanoparticle-mediated combination therapy.Previous studies explored 177 Lu-labeled gold nanoparticles for preclinical nuclear medicine.[7] However,t he clinical translation of the reported nanosystem was impeded because of high and long-term accumulation in the reticuloendothelial system (RES) and low intratumor uptake.T hus,i tr emains ab ig challenge to integrate nanocarrier tumor-targeted delivery and multi-modal imaging using 177 Lu to obtain an anotheranostic agent with high efficiacy.Thespecificity of nanotheranostic reagents to cancer cells is critical for an efficient therapeutic effect with low side effects.[8] Am yriad of strategies have been developed to enhance cancer-targeting specificity,s uch as the conjugation of nanomaterials with target ligands. [9] In ar ecent report, mitochondria targeting emerged as apromising approach for cancer therapy.[10] However,there are several existing fundamental limitations on the design and synthesis of nanomaterials,s uch ...

show abstract

“…In a recent study the combined application of 177 Lu-EC0800 (Figure 3A) and pemetrexed (Figure 1D) was investigated using KB tumor-bearing nude mice (79). Four groups of six athymic nude mice with KB tumor xenografts received only saline (group A), pemetrexed at a high dose (2 × 0.8 mg, group B), 177 Lu-EC0800 (1 × 20 MBq), and pemetrexed at a low dose (1 × 0.4 mg) to reduce renal uptake (group C) or 177 Lu-EC0800 (1 × 20 MBq) and a high dose of pemetrexed (2 × 0.8 mg, group D).…”

Section: Folate Receptor Targeted Radionuclide Therapy – First Resultsmentioning

confidence: 99%

Prospects in Folate Receptor-Targeted Radionuclide Therapy

Müller

Schibli

2013

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

Targeted radionuclide therapy is based on systemic application of particle-emitting radiopharmaceuticals which are directed toward a specific tumor-associated target. Accumulation of the radiopharmaceutical in targeted cancer cells results in high doses of absorbed radiation energy whereas toxicity to non-targeted healthy tissue is limited. This strategy has found widespread application in the palliative treatment of neuroendocrine tumors using somatostatin-based radiopeptides. The folate receptor (FR) has been identified as a target associated with a variety of frequent tumor types (e.g., ovarian, lung, brain, renal, and colorectal cancer). In healthy organs and tissue FR-expression is restricted to only a few sites such as for instance the kidneys. This demonstrates why FR-targeting is an attractive strategy for the development of new therapy concepts. Due to its high FR-binding affinity (KD < 10−9 M) the vitamin folic acid has emerged as an almost ideal targeting agent. Therefore, a variety of folic acid radioconjugates for nuclear imaging have been developed. However, in spite of the large number of cancer patients who could benefit of a folate-based radionuclide therapy, a therapeutic concept with folate radioconjugates has not yet been envisaged for clinical application. The reason is the generally high accumulation of folate radioconjugates in the kidneys where emission of particle-radiation may result in damage to the renal tissue. Therefore, the design of more sophisticated folate radioconjugates providing improved tissue distribution profiles are needed. This review article summarizes recent developments with regard to a therapeutic application of folate radioconjugates. A new construct of a folate radioconjugate and an application protocol which makes use of a pharmacological interaction allowed the first preclinical therapy experiments with radiofolates. These results raise hope for future application of such new concepts also in the clinic.

show abstract

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

Cited by 20 publications

References 41 publications

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Efficient Uptake of ¹⁷⁷Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy

Prospects in Folate Receptor-Targeted Radionuclide Therapy

Contact Info

Product

Resources

About

177Lu-EC0800 Combined with the Antifolate Pemetrexed: Preclinical Pilot Study of Folate Receptor Targeted Radionuclide Tumor Therapy

Cited by 20 publications

References 41 publications

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Folate receptor-targeted radionuclide therapy: preclinical investigation of anti-tumor effects and potential radionephropathy

Efficient Uptake of 177Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy

Prospects in Folate Receptor-Targeted Radionuclide Therapy

Contact Info

Product

Resources

About

Efficient Uptake of ¹⁷⁷Lu‐Porphyrin‐PEG Nanocomplexes by Tumor Mitochondria for Multimodal‐Imaging‐Guided Combination Therapy