Gallium antitumor activity

Hart MM, Adamson RH. 1971. Antitumor activity and toxicity of salts of inorganic group Ilia metals Aluminum, gallium, indium, and thallium. Proc Natl Acad Sci U S A 68 1623-1626. 

Although antitumor activity was found for gallium nitrate in pha.se II clinical trials. " its approved use is for the treatment of cancer-related hypercalcemia." It has proved superior to calcitonin and etidronate in this use. The clinical material is the nonahydratc of Ga(NOt)t. 

Gallium nitrate is approved for treating cancer-related hypercalcemia. It showed antitumor activity fur putienb with lymphoma in phase II trials. - Gallium nitrate probably works in hypercalcemia by inhibiting calcium resorption from bone, although the precise mechanism is unknown. Major side effects include hypocalcemia and nephrotoxicity. On continuous infusion, the drug exhibits biphasic elimination with an a half-life of 8.3 to 26 minutes and a half-life of 6.3 to 95 hours. Between 69 and 91% of the dnsc was recovered in the urine. ... 

Hart MM, Smith CE, Yancey ST and Adamson RH (1971) Toxicity and antitumor activity of gallium nitrate and periodically related metal salts. J Natl Cancer Inst 47 1121-1127. 

Anghileri LJ (1975) On the antitumor activity of gallium and lanthanides. Arzneim-Forsch 25 793-795. 

The antitumor activity of gallium(III) salts (especially nitrate) has been evaluated in phase I and phase II trials [15-18]. The phase II trials have shown that gallium nitrate exhibits antitumor activity in patients with refractory lymphomas [19]. 

The antitumor activity of gallium nitrate has been evaluated in clinical trials because of its ability to concentrate in various tumor tissues [43]. The mechanism for gallium uptake into tumor tissue has been investigated, and when Ga is injected into the bloodstream as either nitrate, chloride, or citrate, it rapidly becomes bound to serum proteins, especially transferrin [44-46]. Gallium-67 transferrin is the active radiopharmaceutical in vivo, and it distributes throughout the blood pool and the Ga concentrates in normal bone, liver, and kidney as well as many types of tumor tissue. 

Autoradiographic studies of gallium-67 salts in rodent tissue show more than 70% of the 67ca activity was localized in the cytoplasm. High concentrations of Ga were observed in the epithelium of renal convoluted tubules.Four Group III-A elements (aluminum, gallium, indium, and thallium) had some antitumor activity but only Ga+3 and, to a lesser extent, In" inhibited tumor growth when the tumor was Innoculated by a... 

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