Table 3.

Overview of some preclinical studies with ²¹³Bi.

Bioconjugate	Key Findings	Cancer Type	Reference
213Bi-anti-EGFR-mAb	The animals survived for an average of 131.8 d after fractionated treatment with 0.46 MBq 213Bi-anti-EGFR-mAb, with 30% remaining for more than 300 days. Even after treatment with 3.7 MBq of 213Bi-anti-EGFR-mAb, no toxic side effects on normal urothelium were observed.	Human bladder carcinoma (local instillation of 213Bi-anti-EGFR-mAb)	[81]
213Bi-69-11 antibody	Antibody 69-11 localized significantly in pancreatic ductal adenocarcinoma cancer (PDAC) xenografts in mice in vivo and ex vivo. TAT of PDAC xenografts with 213Bi-69-11 was effective, safe, and CETN1-specific.	Pancreatic cancer	[15]
213Bi-h8C3 antibody	Treatments with anti-PD-1 antibody alone had a modest impact on tumor size, while the combination therapy with 213Bi-h8C3 resulted in a substantial slowing of tumor development and improved animal survival.	Melanoma	[82]
213Bi-8C3 or 213Bi-6D2 antibody	Antibody binding to melanin was shown to be dependent on both charge and hydrophobic interactions, and in vivo evidence supports the development of 8C3 IgG as a radioimmunotherapy reagent for metastatic melanoma.	Melanoma	[83]
213Bi-DOTATATE	A 10% cell survival of CA20948 was reached at doses of 3 Gy with 213Bi-DOTATATE, a factor six lower than the 18 Gy found for 177Lu-DOTATATE and below the 5 Gy after 137Cs external exposure.	Pancreatic cancer	[56]
213Bi-IMP288-mAb	213Bi-IMP288 cleared from the bloodstream rapidly; blood levels were 0.44 ± 0.28% ID/g 30 min after injection. Except for the kidneys, where uptake was 1.8 ± 1.1% ID/g 30 min after injection, uptake in normal tissues was poor.	Colon cancer	[6]
213Bi-MX35-mAb	The tumor-free fraction in animals given 3 MBq/mL of 213Bi-MX35 was 0.55, while it was 0.78 in animals given 9 MBq/mL of 213Bi-MX35. The tumor-free fraction in the control group treated with unlabeled MX35 was 0.15. There was no significant drop in white blood cell counts or weight loss.	Ovarian cancer	[84]
213Bi-DTPA-PAN-622-mAb	A pilot therapy study with 213Bi-DTPA-PAN-622 demonstrated a significant effect on the primary tumor.	Breast cancer	[85]
213Bi-Anti-hCD138 Antibody	TAT of 7.4 MBq and 11.1 MBq significantly improved survival (p = 0.0303 and p = 0.0070, respectively), whereas HIPEC and HIPEC + TAT treatments did not significantly ameliorate survival as compared with the control group.	Ovarian cancer	[86]
213Bi-DOTA-9E7.4-mAb	TAT with 3.7 MBq of 213Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared with 37 days in the untreated control group and resulted in effected cure in 45% of the animals.	Multiple myeloma (MM)	[87]
213Bi-anti-EGFR-mAb	Treatment with 213Bi-anti-EGFR-mAb resulted in an effective induction of cell death in EJ28Luc and LN18 cells.	Bladder carcinoma	[88]
213Bi-CHX-A’’-DTPA-anti-CD138-mAb	The combined treatment resulted in significant tumor growth suppression and improved survival in the animals.	MM	[89]
213Bi-DTPA-anti-CD38-MAb	Treatment with 213Bi-anti-CD38-mAb suppressed tumor growth in myeloma xenografts by inducing apoptosis in tumor tissue and significantly extended survival relative to controls.	MM	[90]
213Bi-DTPA-Cetuximab	213Bi-cetuximab was found to be significantly more effective in the BRCA-1-mutated triple negative breast cancer (TNBC) cell line HCC1937 than BRCA-1-competent TNBC cell MDA-MB-231. siRNA knockdown of BRCA-1 or DNA-dependent protein kinase, catalytic subunit (DNA-PKcs), a key gene in non-homologous end-joining DSB repair pathway, also sensitized TNBC cells to 213Bi-cetuximab.	Breast cancer	[91]
213Bi-DTPA-anti-CD20-mAb	In CD20-expressing sensitive as well as chemoresistant, beta-radiation resistant, and gamma-radiation resistant NHL cells, 213Bi-anti-CD20 induced apoptosis; activated caspase-3, caspase-2, and caspase-9; and cleaved PARP.	Non-Hodgkin lymphoma	[92]
213Bi-DOTA-biotin	Treated with anti-CD45 Ab-SA conjugate followed by 29.6 MBq of 213Bi- or 90Y-DOTA-biotin, 80% and 20% of mice survived leukemia-free for more than 100 days with limited toxicity, respectively.	Myeloid leukemia	[93]
213Bi-DTPA-C595-mAb and 213Bi-DTPA-PAI2-mAb	After 16 weeks, systemic injections of 213Bi-conjugate at doses of 111, 222, and 333 MBq/kg induced significant tumor growth delay in a dose-dependent manner, compared with the non-specific control at 333 MBq/kg.	Pancreatic cancer	[94]
213Bi-DOTA-biotin	Mice injected with anti-CD20 PTRNT or 22.2 MBq 213Bi-DOTA-biotin had significantly slower tumor growth than controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively).	Non-Hodgkin lymphoma	[95]
213Bi-CHX-A”-DTPA-7.16.4-mAb	In the same animal model, 213Bi radiolabeled immunoliposomes were successful in treating early-stage micrometastases, with median survival times comparable with those obtained with antibody-mediated 213Bi delivery.	Breast cancer	[96]
213Bi-CHX-A”-DTPA-HuCC49ΔCH2	The median survival time after treatment with 213Bi-HuCC49ΔCH2 was 45 days, which was equivalent to the median survival time after treatment with 213Bi-trastuzumab.	Colon carcinoma	[69]
213Bi (213Bi-DTPA-[F3]2)	Except for the kidneys, where 213Bi-DTPA-[F3]2 was present due to renal excretion, 213Bi-DTPA-[F3]2 accumulated significantly in tumors, but only low activities were found in control organs.	Peritoneal carcinomatosis	[97]
213Bi-DTPA-2Rs15d sdAb	Median survival significantly increased when 213Bi-DTPA-2Rs15d was given alone or in combination with trastuzumab.	Ovarian cancer	[5]
213Bi-DTPA-PAI2-mAb	At 2 days and 2 weeks after cell inoculation, no lymphatic cancer spread was observed in the 222 MBq/kg 213Bi-DTPA-PAI2-mAb treated class.	Prostate cancer	[98]