Photonuclear production and antitumor effect of radioactive cisplatin (195mPt)

Bodnar, Elena Nicole; Dikiy, N.P.; Medvedeva, E.P.

doi:10.1007/s10967-015-4053-1

Cited by 16 publications

(14 citation statements)

References 9 publications

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“…This synthesis of Pt-BP was modified compared to previously reported synthesis strategies to facilitate introduction of radioactive 195m Pt atoms by using Pt(NO 3 ) 2 (en) as Pt precursor 29,31 . 195m Pt(NO 3 ) 2 (en) was obtained from Na 2 [ 195m PtCl 4 ], which is the Pt precursor used for synthesis of radioactive cisplatin, thereby allowing for future up-scaling and clinical translation of 195m Pt-BP 23 . Pt hard-to-soft tissue uptake ratio excluding bladder uptake at 1 h. Data from 4-5 mice per group are presented.…”

Section: Discussionmentioning

confidence: 99%

“…Although whole-body radioactivity in 195m Pt-BP treated mice was just 2%ID on day 7 (Supplement Fig. S3), the half-life of 195m Pt (t 1/2 = 4 days) 23,24 enabled quantitative, high resolution SPECT imaging. We further demonstrated 195m Pt-BP specificity towards skeletal sites by an increasing hard-to-soft tissue contrast from 1 h until day 3.…”

Section: Discussionmentioning

confidence: 99%

“…The incorporation of radioactive Pt atoms further enhances the therapeutic properties of Pt-based drugs 21,22 . Notably, radioisotope 195m Pt with a half-life of 4 days, is considered to be the most suitable Pt isotope for radionuclide therapy and medical imaging, since it is a prolific Auger electron emitter and emits a 99 keV gamma for SPECT (single-photon emission computed tomography) imaging, respectively 23,24 . Therefore, targeted delivery of Pt-based chemotherapeutics comprising 195m Pt could potentially increase the therapeutic efficacy of Pt-based drugs.…”

mentioning

confidence: 99%

“…Among the limited number of studies that evaluated the therapeutic properties of 195m Pt, Bodnar et al demonstrated that inhibition of the growth of Ehrlich solid carcinoma by 195m Pt-cisplatin was 30% more effective compared to non-radioactive cisplatin 23 . Nevertheless, Pt based drugs are known to induce systemic toxicity, while the lack of tumor specificity restricts their application for long-term treatment 26,27 .…”

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confidence: 99%

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Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Nadar

Farbod

Schilden

et al. 2020

Sci Rep

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platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195m Pt-BP) complexes to confirm preferential accumulation of these pt-based drugs in metabolically active bone. In vitro nMR studies revealed that release of pt from pt Bp complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. these pt-Bp complexes formed less pt-DnA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of pt from pt-Bp complexes proceeded relatively slow. Subsequently, radioactive 195m pt-Bp complexes were synthesized using 195m pt(no 3) 2 (en) as precursor and injected intravenously into mice. Specific accumulation of 195m pt-Bp was observed at skeletal sites with high metabolic activity using micro-Spect/ct imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195m pt Bp colocalized with calcium in the trabeculae of mice tibia. Most types of tumors, i.e. breast, prostate, lung, kidney, and thyroid, metastasize to bone since its physiological environment facilitates the formation and growth of cancer cells 1,2. These metastases affect healthy bone, which then become the primary cause of mortality 3. Distant metastases are the leading cause of death for both breast and prostate cancer patients, with 65-75% and 90% of these patients developing bone metastases in advanced stages, respectively 4,5. Bone metastases are often associated with accelerated bone resorption leading to complications such as skeletal-related events (SREs), bone pain or hypercalcemia 6,7. Unfortunately, current treatments for bone metastases are limited. Bisphosphonates (BP) and denosumab are most commonly used for palliative treatment to prevent or limit SREs 8. Although such treatments inhibit osteoclast activity and prevent the progression of metastases, they do not kill cancer cells effectively and do not improve the quality of life of patients substantially 9. Consequently, the development of effective therapies to treat bone metastases remains a major clinical challenge.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Nadar

Farbod

Schilden

et al. 2020

Sci Rep

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“…The synergy of two different mechanism may reduce the chemotherapy drug dose, frequently associated with severe or undesirable side effects providing significant benefits for the patients. Initial investigations have showed positive results in this direction [9][10][11][12][13][14][15][16][17][18].…”

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confidence: 99%

Investigation of the potential antitumor radioactive complex of platinum(II) with tetracycline

Leal¹,

Marzano

Pereira-Maia

et al. 2016

J Radioanal Nucl Chem

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The proposal of this work was to investigate the effect of the radioactive complex of platinum(II) with tetracycline, [PtCl 2 (C 22 H 24 N 2 O 8 )]*, or [Tc-Pt(II)]*, on K562 cells-blood human cells of leukemia-and verify if the internal radio-chemotherapy would be able to produce additional effects compared with the non-labelled complex, [PtCl 2 (C 22 H 24 N 2 O 8 )], or [Tc-Pt(II)]. The concentration required to inhibit 50 % of cellular growth, (IC 50 ), was 2.5 ± 0.2 lM for [Tc-Pt(II)]* and 14.5 ± 0.9 lM for the non-labelled molecule [Tc-Pt(II)]. This result suggest that the [Tc-Pt(II)]* could be a potent radiosensitizer evoking a supra additive effect. Treatment using the internal radiochemotherapy may be a useful alternative to reduce the drug concentration required for effective inhibition of the tumor growth.

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