Strong Inhibition of Xenografted Tumor Growth by Low-Level Doses of [32P]ATP

Abstract

The ability of a potential human anti-cancer therapeutic agent to inhibit the growth of xenografted tumors in nude mice has been an established and accepted testing method for several decades. The current report shows that a single, low-level intravenous dose of [32P]ATP significantly inhibits the growth of established xenografted tumors in nude mice. This inhibitory effect becomes appreciable very rapidly, within only five days post-injection and the low dose demonstrates little or no toxicity in the mice. Surprisingly, a narrow dose window of optimum effectiveness is seen, whereby either decreasing or increasing the [32P]ATP dose results in far less growth inhibition. Thus, the intravenous systemic injection of [32P]ATP may represent a simple, potent method to target and inhibit primary human tumors and malignant lesions.

The effect of surgical specimen-derived phosphorus and lead concentrations in non-small cell lung cancer patients on disease course

“…In previous studies evaluating the various functions of phosphorus, mice were injected with human cancer cells as a model, and phosphorus was found to have anti-cancer activity (11)(12)(13). Low-dose phosphorus injections were found to significantly inhibit tumor growth in a murine xenograft model (14). Another study demonstrated that ATP with phosphorus in its structure had good tumor penetration, low immunogenicity and anti-cancer potential due to its pharmacokinetic properties (15).…”

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

“…Beta emitters have been used in the past to kill cancer cells and some of them, such as 131 I and 90 Yttrium, have successfully entered clinical practice 14 , 15 . Cheng et al 16 - 18 have demonstrated that 32 P bound to ATP molecules ( 32 P-ATP) is effective in damaging tumor cells and reducing tumor growth rate in nude mice. The maximum beta energy of electrons emitted by 32 P-ATP lies between that of 131 Iodine and 90 Yttrium with the particle range equal to 5 mm in tissues 19 .…”

Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

“…Human cancer-derived cell lines established in immunocompromised mice are a valuable tool for testing the effectiveness of candidate anti-cancer agents [ 6 – 9 ]. We previously found that a single, low-dose intravenous injection of [ 32 P]ATP significantly inhibits tumor growth for several weeks in murine xenograft models [ 10 , 11 ]. Because ATP is a small naturally-occurring molecule, its radiolabeled form poses some advantages over larger synthetic compounds as a potential anti-cancer therapeutic, including lower immunogenicity, greater tumor penetration, and superior pharmacokinetics [ 12 ].…”