Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103.
B HapplTheresa BalberPetra HeffeterChristoph DenkJ M WelchUlli KoesterC AlliotA-C BonraisinMarie R BrandtFérid HaddadJohannes H SterbaWolfgang KandiollerM MitterhauserMarcus HackerBernhard K KepplerThomas L MindtPublished in: Dalton transactions (Cambridge, England : 2003) (2024)
BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [ 97/103 Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 ( 103 Ru; β - , γ) and ruthenium-97 ( 97 Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [ 103 Ru]BOLD-100 (3 and 30 mg kg -1 ) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, ex vivo autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg -1 ) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [ 103 Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [ 97 Ru]BOLD-100.
Keyphrases
- resting state
- functional connectivity
- computed tomography
- energy transfer
- high resolution
- clinical trial
- end stage renal disease
- chronic kidney disease
- stem cells
- ejection fraction
- contrast enhanced
- image quality
- magnetic resonance
- type diabetes
- randomized controlled trial
- metabolic syndrome
- adipose tissue
- peritoneal dialysis
- young adults
- cancer therapy
- drug delivery
- quantum dots
- cell therapy
- combination therapy
- photodynamic therapy
- pet ct
- phase ii
- atomic force microscopy
- lymph node metastasis