Theranostic Role of ³²P-ATP as Radiopharmaceutical for the Induction of Massive Cell Death within Avascular Tumor Core

Abstract

Drug inaccessibility to vast areas of the tumor parenchyma is amongst the major hurdles for conventional therapies. Treatment efficacy rapidly decreases with distance from vessels and most of the tumor cells survive therapy. Also, between subsequent cycles of treatment, spared cancer cells replace those killed near the vessels, improving their access to nutrients, boosting their proliferation rate, and thus enabling tumor repopulation. Because of their property of "acting at a distance," radioisotopes are believed to overcome the physical barrier of vascular inaccessibility.Methods A novel molecular imaging tool called Cerenkov Luminescence Imaging (CLI) was employed for the detection of Cerenkov radiation emitted by beta particles, allowing in vivo tracking of beta-emitters. More precisely we investigated using a xenograft model of colon carcinoma the potential use of 32P-ATP as a novel theranostic radiopharmaceutical for tracing tumor lesions while simultaneously hampering their growth.Results Our analyses demonstrated that 32P-ATP injected into tumor-bearing mice reaches tumor lesions and persists for days and weeks within the tumor parenchyma. Also, the high-penetrating beta particles of 32P-ATP exert a "cross-fire" effect that induces massive cell death throughout the entire tumor parenchyma including core regions.Conclusion Our findings suggest 32P-ATP treatment as a potential approach to complement conventional therapies that fail to reach the tumor core and to prevent tumor repopulation.

Photodynamic Therapy Using Cerenkov and Radioluminescence Light

“…An important aspect that should be further exploited regarding the use of Cerenkov and radioluminescence light sources, is the possibility of enhancing the cytotoxic effect of PDT. This can be achieved by inducing further damage using the so called radiotherapy cross fire effect obtained with beta emitters like: 90 Y, 177 Lu or 32 P [46]. Another interesting research line should focus on a better integration between the PS with different radioisotopes in order to optimize photon absorption, at the same time reducing the distances and, thus, possible photons loss.…”

Tandem Dye-Doped Nanoparticles for NIR Imaging via Cerenkov Resonance Energy Transfer

“…32 P has been used in the clinic for the treatment of bone metastasis (Gordon Smart, 1965), polycythemia vera (Najean and Rain, 1997), and thrombocythemia (Shetty-Alva and Cheng, 2006). Moreover, the 32 P-ATP was found to show antitumoral activity in preclinical studies (Galiè et al, 2017).…”

Cerenkov Luminescence-Induced NO Release from 32P-Labeled ZnFe(CN)5NO Nanosheets to Enhance Radioisotope-Immunotherapy

“…This new type of 2D nanostructure could be easily labeled with the therapeutic radioisotope 32 P by simply mixing with 32 PO 4 3À anion, yielding ZnNO( 32 P) nanosheets. 32 P with b-ray emission efficiently activated water to generate strong CL, [41][42][43] which subsequently stimulated persistent NO release from these nanosheets. After local administration, as-prepared ZnNO( 32 P) nanosheets showed long-term tumor retention and completely eliminated local tumors.…”