Theranostics 2017; 7(18):4399-4409. doi:10.7150/thno.21403

Research Paper

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

Mirco Galiè1, Federico Boschi2, Ilaria Scambi1, Flavia Merigo1, Pasquina Marzola2, Luisa Altabella3, Umberto Lavagnolo1, Andrea Sbarbati1, Antonello E Spinelli4✉

1. Department of Neuroscience, Biomedicine and Movement, University of Verona, Piazzale L.A. Scuro 10, Verona 37134, Italy;
2. Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy;
3. Medical Physics Department, San Raffaele Scientific Institute, Via Olgettina 60, 20182 Milan, Italy;
4. Experimental Imaging Centre, San Raffaele Scientific Institute, Via Olgettina 60, 20182 Milan, Italy.

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.

Keywords: 32P-ATP radiopharmaceutical, Cerenkov luminescence imaging, magnetic resonance imaging, colorectal adenocarcinoma.

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How to cite this article:
Galiè M, Boschi F, Scambi I, Merigo F, Marzola P, Altabella L, Lavagnolo U, Sbarbati A, Spinelli AE. Theranostic Role of 32P-ATP as Radiopharmaceutical for the Induction of Massive Cell Death within Avascular Tumor Core. Theranostics 2017; 7(18):4399-4409. doi:10.7150/thno.21403. Available from http://www.thno.org/v07p4399.htm