RDC Development for Bladder Cancer

As a new type of cancer treatment drug, RDC (Radionuclide Drug Conjugate) is guided to the cancer site by targeted molecules and treats the bladder cancer by radionuclides.

Introduction into Bladder Cancer

Bladder Cancer (BCa) is a common malignancy, as the seventh most frequent malignancy in males and the seventeenth most frequent malignancy in females, ranging from unaggressive and noninvasive tumors, diagnosed in 549,393 patients and 199,922 succumbed to the disease worldwide in 2018 worldwide. The most common symptom of bladder cancer is visible hematuria, as well as isolated microscopic hematuria, showing ≥3 red blood cells per high-power field, irritative voiding symptoms, and a tumor incidentally discovered on imaging.

Epidemiology of Bladder Cancer

According to WHO (World Health Organization) reports, the incidence of bladder cancer varies significantly among different geographical regions resulting from the development level of the country which may be caused by tobacco smoking abuse, obesity, alcohol consumption, and overuse of red meat.

Among all these pathogenic factors, cigarette smoking remains the most prevalent risk factor, responsible for half of all bladder cancer cases, with the magnitude of harm corresponding to smoking intensity and duration.

Occupational exposures have long been associated with bladder cancer risk, which includes processing paint, rubber, petroleum products, and dye workers, as well as electrical and chemical process workers with about 8% attributed to such exposures.

Types of Bladder Cancer and Traditional Therapies

Bladder cancer can be categorized as a high-grade vs low-grade disease based on standardized histomorphologic features according to WHO reports. Based on the depth of bladder wall invasion, bladder cancer can be divided into two classes, tumors of which isolated to the urothelium (stage Ta) and the lamina propria (stage T1) are considered NMIBC (Non–Muscle-Invasive Bladder Cancer), while tumors of which with muscle invasion (stage T2) or beyond (stages T3 and T4), called MIBC (Muscle-Invasive Bladder Cancer)

• Therapies for NMIBC
  TURBT (Transurethral Resection of the Bladder Tumor) is the mainstream therapy for non-muscle invasive diseases, including NMIBC. Besides, EBRT (En Bloc Bladder Tumor Removal) has been introduced and is approved to be applied in the NMIBC therapy worldwide. The standard therapy for bladder cancer is intravesical instillation of BCG (Bacillus Calmette-Guérin), an attenuated strain of Mycobacterium Bovis, which can induce a local immune response in the bladder to eradicate tumor cells to conduct immunotherapy for over 30 years.
• Therapies for MIBC
  RC (Radical Removal of the Bladder with Concomitant Meticulous Pelvic Lymph Node) dissection is the gold standard approach for MIBC treatment for many decades. However, the majority of patients recur with distant metastases and half of them die of bladder cancer within five years.

Hence, Novel bladder cancer treatment is required urgently. The advanced RDC (Radionuclide Drug Conjugate) emerges as a leader in bladder cancer treatment.

Bladder Cancer Treatment with RDC

However new effective therapies are urgently needed to replace BCG treatment since 60 – 70% of patients relapse and are consequently classified as BCG-unresponsive. Intravesical instillation of RDC, known as ²¹³Bi-anti-EGFR MAb, shows therapeutic efficacy, composed of the alpha-emitter ²¹³Bi and a Mab (Monoclonal Antibody) targeting overexpressed EGFR (Epidermal Growth Factor Receptor) on bladder cancer.

Fig.1 Distribution of ²¹³Bi-anti-EGFR MAb after instillation by SPECT/CT imaging.
(Autenrieth, et al., 2018, Eur J Nucl Med Mol Imaging)

Reference

1. Autenrieth, M. E., Seidl, C., Bruchertseifer, F., Horn, T., Kurtz, F., Feuerecker, B., ... & Morgenstern, A. (2018). Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study. European Journal of Nuclear Medicine and Molecular Imaging, 45(8), 1364-1371.