Aminocarboxylate complexes and octreotide complexes with no carrier added 177Lu, 166Ho and 149Pm

Li, Wen Ping; Smith, Charles J.; Cutler, Cathy S.; Hoffman, Timothy J.; Ketring, Alan R.; Jurisson, Silvia S.

doi:10.1016/s0969-8051(02)00418-3

Cited by 20 publications

(9 citation statements)

References 11 publications

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“…The most common polyaminocaboxylate chelator utilized in NTR1-targeted agent design is diethylenetriamine pentaacetic acid (DTPA)[11,28–30]. Unfortunately, DTPA forms a complex with 177 Lu that in known to be unstable in vivo [31]. Conversely, DOTA, due to its cyclic nature and steric inhibition, is known to form in vivo stable 177 Lu complexes, as demonstrated by numerous preclinical and clinical studies[24,27,31].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, DTPA forms a complex with 177 Lu that in known to be unstable in vivo [31]. Conversely, DOTA, due to its cyclic nature and steric inhibition, is known to form in vivo stable 177 Lu complexes, as demonstrated by numerous preclinical and clinical studies[24,27,31]. At the same time, DOTA, when placed too closely to the pharmacophore, has been shown to sterically inhibit the efficacy of receptor-targeted peptides[17,32].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting

Jia

Shi

Zhou

et al. 2015

Nuclear Medicine and Biology

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Introduction Neurotensin receptor 1 (NTR1) is overexpressed in many cancers types. Neurotensin (NT), a 13 amino acid peptide, is the native ligand for NTR1 and exhibits high (nM) affinity to the receptor. Many laboratories have been investigating the development of diagnostic and therapeutic radiopharmaceuticals for NTR1-positive cancers based on the NT peptide. To improve the biological performance for targeting NTR1, we proposed NT analogs with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelation system and different lengths of spacers. Methods We synthesized four NTR1-targeted conjugates with spacer lengths from 0 to 9 atoms (null (N0), β-Ala-OH (N1), 5-Ava-OH (N2), and 8-Aoc-OH (N3)) between the DOTA and the pharmacophore. In vitro competitive binding, internalization and efflux studies were performed on all four NT analogs. Based on these findings, metabolism studies were carried out on our best performing conjugate, 177Lu-N1. Lastly, in vivo biodistribution and SPECT/CT imaging studies were performed using 177Lu-N1 in an HT-29 xenograft mouse model. Results As shown in competitive binding assay, the NT analogs with different spacers (N1, N2 and N3) exhibited lower IC50 values than the NT analog without a spacer (N0). Furthermore, N1 revealed higher retention in HT-29 cells with more rapid internalization and slower efflux than the other NT analogs. In vivo biodistribution and SPECT/CT imaging studies of 177Lu-N1 demonstrated excellent accumulation (3.1 ± 0.4 %ID/g) in the NTR1-positive tumors at 4 h post-administration. Conclusions The DOTA chelation system demonstrated some modest steric inhibition of the pharmacophore. However, the insertion of a 4-atom hydrocarbon spacer group restored optimal binding affinity of the analog. The in vivo assays indicated that 177Lu-N1 could be used for imaging and radiotherapy of NTR1-positive tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting

Jia

Shi

Zhou

et al. 2015

Nuclear Medicine and Biology

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“…153 Sm and 166 Ho complexes with tetraazamacrocycles linked to different biomolecules, such as monoclonal antibodies or peptides, have also been considered excellent candidates for therapy and are under investigation [16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

13- and 14-membered macrocyclic ligands containing methylcarboxylate or methylphosphonate pendant arms: Chemical and biological evaluation of their 153Sm and 166Ho complexes as potential agents for therapy or bone pain palliation

Marques¹,

Gano²,

Campello³

et al. 2006

Journal of Inorganic Biochemistry

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“…The aminophosphonate chelate ethylenediaminetetramethylenephosphonic acid (EDTMP) was used to develop 153 Sm-EDTMP (Quadramet®) as a bone pain palliation agent; 1,4,7,10-tetraazacyclododecane-1,4,7,10-methylenephosphonic acid (DOTMP) has been investigated more recently to form a more kinetically inert complex with 166 Ho [116, 118]. Several excellent reviews on the lanthanide chemistry of radiopharmaceuticals have been published [27, 116, 117, 121]. …”

Section: Radiometal Chelate Considerationsmentioning

confidence: 99%

Inorganic chemistry in nuclear imaging and radiotherapy: current and future directions

et al. 2012

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Summary Radiometals play an important role in diagnostic and therapeutic radiopharmaceuticals. This field of radiochemistry is multidisciplinary, involving radiometal production, separation of the radiometal from its target, chelate design for complexing the radiometal in a biologically stable environment, specific targeting of the radiometal to its in vivo site, and nuclear imaging and/or radiotherapy applications of the resultant radiopharmaceutical. The critical importance of inorganic chemistry in the design and application of radiometal-containing imaging and therapy agents is described from a historical perspective to future directions.

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Aminocarboxylate complexes and octreotide complexes with no carrier added 177Lu, 166Ho and 149Pm

Cited by 20 publications

References 11 publications

Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting

Evaluation of DOTA-chelated neurotensin analogs with spacer-enhanced biological performance for neurotensin-receptor-1-positive tumor targeting

13- and 14-membered macrocyclic ligands containing methylcarboxylate or methylphosphonate pendant arms: Chemical and biological evaluation of their 153Sm and 166Ho complexes as potential agents for therapy or bone pain palliation

Inorganic chemistry in nuclear imaging and radiotherapy: current and future directions

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