Preparation, characterization and biological evaluation of99mTc(CO)3-labelled cyclic polyamines

Vanbilloen, H.; Eraets, K; Evens, Nele; Terwinghe, Christelle; Rattat, Dirk; Bormans, Guy; Mortelmans, Luc; Verbruggen, A.

doi:10.1002/jlcr.1012

Cited by 7 publications

(7 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Determination of the distribution coefficient was carried out by a shake flask method [31]. An aliquot (25 mL) of 99m Tc-5, 99m Tc-8 or 99m Tc-11A and 99m Tc-11B (185 kBq/mL) was added to a polypropylene tube (5 mL) (Sarstedt, Nümbrecht, Germany) containing 2 mL of 0.025 M sodium phosphate buffer pH 7.4 and 2 mL 1octanol.…”

Section: Log D 1àoctanol/phosphate Buffer Ph 74 Determinationmentioning

confidence: 99%

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

Akurathi

Dubois

Celen

et al. 2014

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

In vivo visualization of tumor hypoxia related markers, such as the endogenous transmembrane protein CA IX may lead to novel therapeutic and diagnostic applications in the management of solid tumors. In this study 4-(2-aminoethyl)benzene sulfonamide (AEBS, K(i) = 33 nM for CA IX) has been conjugated with bis(aminoethanethiol) (BAT) and mercaptoacetyldiglycine (MAG2) tetradendate ligands and the conjugates radiolabelled with (99m)Tc, to obtain anionic and neutral (99m)Tc-labeled sulfonamide derivatives, respectively. The corresponding rhenium analogues were also prepared and showed good inhibitory activities against hCA IX (K(i) = 59-66 nM). In addition, a second generation bis AEBS was conjugated with MAG2 and labeled with (99m)Tc, and the obtained diastereomers were also evaluated in targeting CA IX. Biodistribution studies in mice bearing HT-29 colorectal xenografts revealed a maximum tumor uptake of <0.5% ID/g at 0.5 h p.i for all the tracers. In vivo radiometabolite analysis indicated that at 1 h p.i. MAG₂ tetradendate ligands were more stable in plasma (>50% intact) compared to the neutral complex (28% intact). This preliminary data suggest that negatively charged (99m)Tc-labeled sulfonamide derivatives with modest lipophilicity and longer circulation time could be promising markers to target CA IX.

show abstract

Section: Log D 1àoctanol/phosphate Buffer Ph 74 Determinationmentioning

confidence: 99%

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

Akurathi

Dubois

Celen

et al. 2014

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…NOTA and NODAGA chelators can accommodate various radiometals, most commonly the PET (positron emission tomography) radionuclides 68 Ga and 64 Cu, and result in hydrophilic complexes of good stability. Interestingly, TACN and its derivatives are capable of coordinating the fac -[M(CO) 3 ] + core, leading to stable complexes in vitro and in vivo . − The crystal structure of fac -[Re(CO) 3 (TACN)] + revealed complexation via the (N,N,N) donor set in a distorted octahedral conformation with facial CO groups and formation of five-membered chelate rings . We published the first examples of [ 99m Tc][Tc(CO) 3 (TACN)]-functionalized bombesin derivatives, which displayed high in vitro binding affinity for gastrin-releasing peptide receptors (GRPR) in prostate cancer cells (PC-3) .…”

Section: Introductionmentioning

confidence: 99%

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

et al. 2018

View full text Add to dashboard Cite

With the long-term goal of developing theranostic agents for applications in nuclear medicine, in this work we evaluated the well-known NOTA and NODAGA chelators as bifunctional chelators (BFCs) for the [99mTc/186Re]Tc/Re-tricarbonyl core. In particular, we report model complexes of the general formula fac-[M(L)(CO)3]+ (M = Re, 99mTc, 186Re) where L denotes NOTA-Pyr (1) or NODAGA-Pyr (2), which are derived from conjugation of NOTA/NODAGA with pyrrolidine (Pyr). Further, as proof-of-principle, we synthesized the peptide bioconjugate NODAGA-sst2-ANT (3) and explored its complexation with the fac-[Re(CO)3]+ and fac-[99mTc][Tc(CO)3]+ cores; sst2-ANT denotes the somatostatin receptor (SSTR) antagonist 4-NO2-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH2. Rhenium complexes Re-1 through Re-3 were synthesized and characterized spectroscopically, and receptor binding affinity was demonstrated for Re-3 in SSTR-expressing cells (AR42J, IC50 = 91 nM). Radiolabeled complexes [99mTc]Tc/[186Re]Re-1/2 and [99mTc]Tc-3 were prepared in high radiochemical yield (>90%, determined by radio-HPLC) by reacting [99mTc]/[186Re][Tc/Re(OH2)3(CO)3]+ with 1–3 and correlated well with the respective Re-1 through Re-3 standards in comparative HPLC studies. All radiotracers remained intact through 24 h (99mTc-labeled complexes) or 48 h (186Re-labeled complexes) against 1 mM l-histidine and 1 mM l-cysteine (pH 7.4, 37 °C). Similarly, rat serum stability studies displayed no decomposition and low nonspecific binding of 9–24% through 4 h. Biodistribution of [99mTc]Tc-3 in healthy CF-1 mice demonstrated a favorable pharmacokinetic profile. Rapid clearance was observed within 1 h post-injection, predominantly via the renal system (82% of the injected dose was excreted in urine by 1 h), with low kidney retention (% ID/g: 11 at 1 h, 5 at 4 h, and 1 at 24 h) and low nonspecific uptake in other organs/tissues. Our findings establish NOTA and NODAGA as outstanding BFCs for the fac-[M(CO)3]+ core in the design and development of organometallic radiopharmaceuticals. Future in vivo studies of [99mTc]Tc- and [186Re]Re-tricarbonyl complexes of NODAGA/NOTA-biomolecule conjugates will further probe the potential of these chelates for nuclear medicine applications in diagnostic imaging and targeted radiotherapy, respectively.

show abstract

“…These include NOTA and NODAGApolycarboxylate derivatives of 1,4,7-triazacyclononane which can coordinate to the fac-[M(CO) 3 ] + core, resulting in stable, hydrophilic complexes. 173,174 In 2018, Makris et al first explored [ 99m Tc] Tc/[ 186 Re]Re-tricarbonyl core with NOTA and NODAGA BFCs conjugated to sst 2 -ANT, the somatostatin receptor antagonist 4-NO 2 -Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH 2 . 175 They were prepared in high radiochemical yields and biodistribution studies in healthy mice with the [ 99m Tc] Tc(CO) 3 (NODAGA)-peptide bioconjugate revealed outstanding pharmacokinetics, such as negligible non-specific organ uptake and rapid renal clearance after 1 hour.…”

Section: Rsc Medicinal Chemistry Reviewmentioning

confidence: 99%

Bifunctional chelators for radiorhenium: past, present and future outlook

et al. 2022

View full text Add to dashboard Cite

show abstract

Preparation, characterization and biological evaluation of99mTc(CO)3-labelled cyclic polyamines

Cited by 7 publications

References 19 publications

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

Bifunctional chelators for radiorhenium: past, present and future outlook

Contact Info

Product

Resources

About

Preparation, characterization and biological evaluation of99mTc(CO)3-labelled cyclic polyamines

Cited by 7 publications

References 19 publications

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

Development and biological evaluation of 99mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

NOTA and NODAGA [99mTc]Tc- and [186Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

Bifunctional chelators for radiorhenium: past, present and future outlook

Contact Info

Product

Resources

About

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate