Emerging Trends for Radioimmunotherapy in Solid Tumors

Jain, Maneesh; Gupta, Suprit; Kaur, Sukhwinder; Ponnusamy, Moorthy P.; Batra, Surinder K.

doi:10.1089/cbr.2013.1523

Cited by 17 publications

(15 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The effectiveness of combining radionuclides and monoclonal antibodies [31] has been well-documented for both hematopoietic and solid tumors [32-34]. The incorporation of RIT in the treatment of OS is founded on its reliable surface overexpression of IGF2R.…”

Section: Discussionmentioning

confidence: 99%

Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R)

Geller

Morris

Revskaya

et al. 2016

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Introduction Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30 years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. Methods Binding efficiency of the Rhenium-188(188Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis. Biodistribution studies were performed in heterotopic murine osteosarcoma xenografts. Tumor growth was compared over a 24-day period post-treatment between mice randomized to receive 188Re-labeled IGF2R-specific murine mAb MEM-238 (188Re-MEM-238) or one of three controls—188Re-labeled isotype control mAb, unlabeled MEM-238,or no treatment. Results Results demonstrate the radioimmunoconjugate had a high binding constant to IGF2R. Both 188Re-MEM-238 and the isotype control had similar initial distribution in normal tissue. After 48 hours 188Re-MEM-238 exhibited a 1.8 fold selective uptake within tumor compared to the isotype control (p=0.057). Over 24 days, the tumor growth ratio was suppressed in animals treated with RIT compared to unlabeled and untreated controls (p=0.005) as demonstrated by a 38% reduction of IGF2R expressing osteosarcoma cells in the RIT group (p=0.002). Conclusions In conclusion, given the lack of new effective therapies in osteosarcoma, additional investigation into this target is warranted. Advances in Knowledge High expression of IGF2R on osteosarcoma tumors, paired with the specificity and in vivo anti-cancer activity of 188Re-labeled IGF2R-specific mAb suggests that IGF2R may represent a novel therapeutic target in the treatment of osteosarcoma. Implications for Patient Care This targeted approach offers the benefits of being independent of a specific pathway, a resistance mechanism, and/or an inherent biologic tumor trait and therefore is relevant to all OS tumors that express IGF2R.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R)

Geller

Morris

Revskaya

et al. 2016

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…Application of RIT to treat solid tumors has been an attractive idea because it can target both known and occult lesions. Although RIT has been successfully applied to treat lymphoma, it has been generally facing a number of obstacles in treating solid tumors including, among others, heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance [ 50 ]. Indeed, very few trials to treat solid tumors by RIT have progressed beyond Phase II (see e.g., ref.…”

Section: Discussionmentioning

confidence: 99%

“…Efforts have been continually devoted to developing and optimizing strategies to surmount the obstacles for and to enhance the clinical response of solid tumors to RIT (see e.g., refs. [ 50 , 51 , 52 ]). The zebrafish embryo model can be useful for studying the properties of rescue effect in these tumors including, e.g., the effects of non-uniform radiation doses delivered to the tumors.…”

Section: Discussionmentioning

confidence: 99%

Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

Lam

Fung

Han

et al. 2015

IJMS

View full text Add to dashboard Cite

The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed.

show abstract

“…Several reviews have discussed the use of alpha-emitting radionuclides in medicine [70][71][72]. The current review will specifically focus on the current trends and present use of radium in radiopharmaceutical applications.…”

Section: Radium and Targeted Alpha Therapymentioning

confidence: 99%

The Radiochemical and Radiopharmaceutical Applications of Radium

2016

View full text Add to dashboard Cite

This review focuses on the chemistry and application of radium isotopes to environmental monitoring, analytical, and medicinal uses. In recent years, radium has been used primarily as a tracer to study the migration of radioactive substances in environmental systems. Tracing the naturally occurring radium isotopes in mineral and water sources allows for the determination of source location, residence time, and concentrations. An understanding of the concentration of radionuclides in our food and water sources is essential to everyone's health as alpha particle decay is highly damaging in vivo. Due to this high radiobiological effectiveness, there is increased interest in using alpha-emitting radionuclides to prepare new, therapeutic radiopharmaceutical drugs. Selected studies from the recent literature are provided as examples of these modern applications of radium isotopes.

show abstract

Emerging Trends for Radioimmunotherapy in Solid Tumors

Cited by 17 publications

References 93 publications

Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R)

Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R)

Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

The Radiochemical and Radiopharmaceutical Applications of Radium

Contact Info

Product

Resources

About