Evolving Important Role of Lutetium-177 for Therapeutic Nuclear Medicine

Pillai, Ambikalmajan M.R.; Knapp, F. F.

doi:10.2174/1874471008666150312155959

Cited by 35 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lutetium-177 ( 177 Lu) is a medium-energy β-emitter (E max of 498.3 keV) and low-energy gamma emitter (Eγ max of 208 keV), which decays with a half-life of approximately 6.6 days [74]. The first paper describing 177 Lu as a potential diagnostic agent was published in 1968 for skeletal imaging purposes [75].…”

Section: Radiolabeled Bbn Derivatives In Preclinical Studiesmentioning

confidence: 99%

Radiolabeled bombesin derivatives for preclinical oncological imaging

Ferreira

Fuscaldi

Townsend

et al. 2017

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Despite efforts, cancer is still one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths each year, according to the World Health Organization. Among the strategies to reduce cancer progression and improving its management, implementing early detection technologies is crucial. Based on the fact that several types of cancer cells overexpress surface receptors, small molecule ligands, such as peptides, have been developed to allow tumor identification at earlier stages. Allied with imaging techniques such as PET and SPECT, radiolabeled peptides play a pivotal role in nuclear medicine. Bombesin, a peptide of 14 amino acids, is an amphibian homolog to the mammalian gastrin-releasing peptide (GRP), that has been extensively studied as a targeting ligand for diagnosis and therapy of GRP positive tumors, such as breast, pancreas, lungs and prostate cancers. In this context, herein we provide a review of reported bombesin derivatives radiolabeled with a multitude of radioactive isotopes for diagnostic purposes in the preclinical setting. Moreover, since animal models are highly relevant for assessing the potential of clinical translation of this radiopeptides, a brief report of the currently used GRP-positive tumor-bearing animal models is described.

show abstract

Section: Radiolabeled Bbn Derivatives In Preclinical Studiesmentioning

confidence: 99%

Radiolabeled bombesin derivatives for preclinical oncological imaging

Ferreira

Fuscaldi

Townsend

et al. 2017

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

show abstract

“…The low energy β − emissions, a half-life of 6.64 days and the emission of low energy and low abundance γ-rays has made 177 Lu a solid candidate to be the most applied therapeutic radionuclide by 20201. Its low energy β − particles with a tissue penetration of less than 3 mm make it suitable for targeting small primary and metastatic tumours, like prostate, breast, melanoma, lung and pancreatic tumours, for bone palliation therapy and other chronic diseases234.…”

mentioning

confidence: 99%

“…After the success of the pioneering work carried out at Erasmus Medical Centre for treating neuroendocrine tumours with 177 Lu-labeled peptides, the treatment is now applied at that hospital to more than 400 patients per year367. Further, the demand of 177 Lu is expected to grow, since it is now approved for use in prostate cancer treatment and many other treatments are in advanced clinical trial stages8910.…”

mentioning

confidence: 99%

Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects

Bhardwaj

Meer

Das

et al. 2017

Sci Rep

View full text Add to dashboard Cite

177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β− emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.

show abstract

“…Hf by emission of βparticles with a maximum energy of 497 keV, which is suitable for treating small-and mediumsized tumors [20][21][22]. It also emits gamma photons in low abundances (113 keV (6.4%) and 208 keV (11%)) which provides an additional advantage of executing simultaneous pharmacokinetic and dosimetric evaluation without adding much additional radiation dose burden to the patients [18,19,23].…”

Section: Decays To Stable 177mentioning

confidence: 99%

Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with ¹⁷⁷Lu-Acridine

Ghosh

Das

Suman

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Objective. A DNA intercalating agent reversibly stacks between the adjacent base pairs of DNA and thus is expected to exhibit preferential localization in the tumorous lesions as tumors are associated with enhanced DNA replication. Therefore, radiolabeled DNA intercalators are supposed to have potential to be used in targeted tumor therapy. Working in this direction, an attempt was made to radiolabel 9-aminoacridine, a DNA intercalator, with 177Lu, one of the most useful therapeutic radionuclides, and study the potential of 177Lu-acridine in targeted tumor therapy. Experiments. 9-Aminoacridine was coupled with p-NCS-benzyl-DOTA to facilitate radiolabeling, and the conjugate was radiolabeled with 177Lu. Different reaction parameters were optimized in order to obtain 177Lu-acridine complex with maximum radiochemical purity. In vitro stability of the radiolabeled complex was studied in normal saline and human blood serum. Biological behavior of the radiolabeled agent was studied both in vitro and in vivo using the Raji cell line and fibrosarcoma tumor-bearing Swiss mice, respectively. Results. 177Lu-acridine complex was obtained with ~100% radiochemical purity under the optimized reaction conditions involving incubation of 1.5 mg/mL of ligand with 177Lu (1 mCi, 37 MBq) at 100°C at pH ~5 for 45 minutes. The complex maintained a radiochemical purity of >85% in saline at 6 d and >70% in human serum at 2 d postpreparation. In vitro cellular study showed uptake of the radiotracer (5.3±0.13%) in the Raji cells along with significant cytotoxicity (78.06±2.31% after 6 d). Biodistribution study revealed considerable accumulation of the radiotracer in tumor 9.98±0.13 %ID/g within 1 h postadministration and retention therein till 6 d postadministration 4.00±0.16 %ID/g with encouraging tumor to nontarget organ uptake ratios. Conclusions. The present study, although preliminary, indicates the potential of 177Lu-acridine and thus radiolabeled DNA intercalators in targeted tumor therapy. However, further detailed evaluation is required to explore the actual potential of such agents in targeted tumor therapy.

show abstract

Evolving Important Role of Lutetium-177 for Therapeutic Nuclear Medicine

Cited by 35 publications

References 0 publications

Radiolabeled bombesin derivatives for preclinical oncological imaging

Radiolabeled bombesin derivatives for preclinical oncological imaging

Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects

Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with ¹⁷⁷Lu-Acridine

Contact Info

Product

Resources

About

Evolving Important Role of Lutetium-177 for Therapeutic Nuclear Medicine

Cited by 35 publications

References 0 publications

Radiolabeled bombesin derivatives for preclinical oncological imaging

Radiolabeled bombesin derivatives for preclinical oncological imaging

Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects

Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with 177Lu-Acridine

Contact Info

Product

Resources

About

Targeted Tumor Therapy with Radiolabeled DNA Intercalator: A Possibility? Preclinical Investigations with ¹⁷⁷Lu-Acridine