Radiolabeled Somatostatin Receptor Antagonists

Fani, Melpomeni; Maecke, Helmut R.

doi:10.1002/9781119031659.ch27

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“…The half-maximal inhibitory concentration (IC 50 value) was determined to be 91 ± 7 nM (Figure ), while somatostatin-14 had a value of 8 ± 4 nM under the same experimental protocol. This SSTR binding affinity is lower than previously reported Re(NSN)(CO) 3 -sst 2 -ANT and Re(NSO)(CO) 3 -sst 2 -ANT (unpublished data) complexes by our group and the optimal IC 50 value of <30 nM described in the literature . Nevertheless, pharmacokinetics plays a dominant role in regards to tumor uptake in vivo .…”

Section: Resultscontrasting

confidence: 58%

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

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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.

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Section: Resultscontrasting

confidence: 58%

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

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Radiolabeled Somatostatin Receptor Antagonists

Cited by 1 publication

References 35 publications

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

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

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Radiolabeled Somatostatin Receptor Antagonists

Cited by 1 publication

References 35 publications

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

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

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

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