Thyroid cancer is the most common malignancy of endocrine tissues, disproportionally affecting women, and is one of the few cancers greatly increasing in incidence & prevalence for unknown reasons. A very aggressive form of this cancer may result from nuclear accidents like Chernobyl & Fukushima, increasing proximity of nuclear waste storage sites, or from nuclear explosions including those that could result from well-publicized terrorist intentions, a vitally important & timely global health problem. Though usually not fatal, most higher risk patients require lifelong diagnostic surveillance with radioiodine imaging to detect residual tumors requiring subsequent therapy with 131I to prevent severe, often underestimated morbidity & less common mortality. One of the PIs (BW), while an intramural lab chief at NIDDK, co-invented, co-developed & licensed to Genzyme recombinant human (rh)TSH (Thyrogen), with current annual sales over $200 Million. Thyrogen is currently approved for enhancing imaging with radioiodine, stimulation of the serum marker thyroglobulin (Tg), & normal thyroid remnant ablation. However, because of its short half-life & lack of equivalent stimulation to thyroid hormone withdrawal producing hypothyroidism, Thyrogen is not approved for thyroid cancer treatment. Moreover, there is currently no method to image or treat the increasing number up to 20% of much more aggressive, more radio-resistant cancers which cause major morbidity and decreased quality of life not totally reflected in cancer mortality figures. The PIs have previously invented a novel 1st & 2nd generation superagonist analogs of rhTSH, the earliest non-commercialized drug candidates, of higher potency, initially licensed by the PIs from NIDDK. The current proposal is related to a totally novel 3rd generation analog, the proposed final drug candidate, with greatly increased half-life achieved with a totally novel dual neoglycosylation insert that for the first time synergizes with the superagonist mutations to achieve much higher in vitro & vivo potency, as well as for the 1st time maximal efficacy in responsive & radio-resistant cancers with fewer, less painful subcutaneous injections, without any toxicity or immunogenicity. TR14601 or TR14701 greatly superior to Thyrogen, all previous Trophogen analogs & will allow greatly improved diagnosis and treatment of patients with thyroid cancer, including many of those currently viewed as radio-resistant for which there is no current therapy. Trophogen analogs, & thus provides much superior patent protection for major commercialization advantages over Thyrogen and any possible future biosimilars. We now provide compelling preliminary in vivo imaging & thyroglobulin (Tg) biomarker stimulation data demonstrating the vast superiority of two newest analogs to Thyrogen & to 2nd generation analogs in normal thyroid, as well as two novel, highly relevant xenograft tumor models. We believe these compelling preliminary in vivo imag...