a cyclic 9-amino acid peptide and binds to p32 proteins on activated macrophages
[45]. Yet, the in vivo plaque accumulation of monomeric [
18 F]FBA-LyP-1 was low
(0.31 ± 0.05%ID/g). Multivalent peptides increase the binding avidity of targeting
biomarker [46]. To increase the avidity of LyP-1 constructs to p32, dendritic form
of LyP-1 ((LyP-1)4-dendrimer) was synthesized.
64
Cu was labeled via chelator
6-BAT (6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N,N′,
N″,N″′-tetraacetic acid) on (LyP-1)4-dendrimer for PET/CT imaging. Radioactivity
of the LyP-1-dendrimer was 1.1 ± 0.26%ID/g in the aorta of ApoE-null mice
having developed atherosclerosis on a high fat diet for 6 months.
Radionuclide-based theranostic strategy have been investigated by radiolabeling
of dendrimers with radionuclides emitting both beta and gamma ray simultaneously
such as
177
Lu,
131 I, and
188 Re. Dendrimers were radiolabeled with
177 Lu after
conjugation with DOTA [47]. Biodistribution studies of
177 Lu-DOTA-dendrimers
in C57BL/6 melanoma-bearing mice showed a high uptake in liver (20%ID/g), and
spleen (18%ID/g). The blood activity decreased by half in 4 h through renal system.
The tumor uptake was 5%ID/g and remained constant over 24 h.
Chlorotoxin (CTX)-conjugated multifunctional dendrimers labeled with
radionuclide
131 I were synthesized and utilized for targeted SPECT imaging and
radiotherapy of cancer [48]. Amine-terminated PAMAM dendrimers of G5 were
used as a platform. The dendrimers was conjugated with PEG, CTX, and 3-(4′hydroxyphenyl)propionic acid-OSu (HPAO). CTX selectively interacts with matrix
metallopeptidase 2 (MMP-2) which are specifically upregulated in gliomas. The
hydrodynamic size of them were 233.5 nm and the surface potential of the G5.
NHAc-HPAO-(PEG-CTX)-(mPEG) dendrimers was +25.9 mV. The dendrimer
platform was labeled with
131 I using the chloramine-T method through the phenol
group of HPAO moiety. This theranostic dendrimer platform had an ability for
targeted SPECT imaging and radiotherapy of an MMP-2 overexpressing C6 glioma
mouse model.
G4 poly-L-lysine dendrimer was radiolabeled with
188 Re via nitro-imidazole
chelating ligand (ImDendrim) [49]. Nude mice bearing hepatocellular carcinoma
HepG2 xenograft tumors were treated with a 0.1 ml of
188 Re-ImDendrim at doses
of 37, 74, 92.5 and 111 MBq by a single intratumoral injection. After 3 and 24 h
post in situ administration of
188 Re-ImDendrim, SPECT/CT imaging was done. At
24 h post injection of
188 Re-ImDendrim, almost total administered radioactivity
was retained locally in the injection site. There were no significant diffusion outside
the injection area and no significant uptake in various organs including lungs, heart,
liver, kidneys and brain (Fig. 5.5). The cationic poly-L-lysine groups of dendrimer
limit its diffusion rate and showed high retention in the site of injection.
188 Re-ImDendrim treated group showed significant anti-tumor property even with
the lowest dose of 37 MBq per mouse. In comparison, injection of nonradioactive
ImDendrim or free
188 Re did not result in any anti-tumor effect. In situ introduction
of
188 Re-ImDendrim is in phase 1 clinical trial for treatment of inoperable liver
cancers which are non-responding to conventional therapy.
116
K. W. Kang and M. G. Song
[45]. Yet, the in vivo plaque accumulation of monomeric [
18 F]FBA-LyP-1 was low
(0.31 ± 0.05%ID/g). Multivalent peptides increase the binding avidity of targeting
biomarker [46]. To increase the avidity of LyP-1 constructs to p32, dendritic form
of LyP-1 ((LyP-1)4-dendrimer) was synthesized.
64
Cu was labeled via chelator
6-BAT (6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N,N′,
N″,N″′-tetraacetic acid) on (LyP-1)4-dendrimer for PET/CT imaging. Radioactivity
of the LyP-1-dendrimer was 1.1 ± 0.26%ID/g in the aorta of ApoE-null mice
having developed atherosclerosis on a high fat diet for 6 months.
Radionuclide-based theranostic strategy have been investigated by radiolabeling
of dendrimers with radionuclides emitting both beta and gamma ray simultaneously
such as
177
Lu,
131 I, and
188 Re. Dendrimers were radiolabeled with
177 Lu after
conjugation with DOTA [47]. Biodistribution studies of
177 Lu-DOTA-dendrimers
in C57BL/6 melanoma-bearing mice showed a high uptake in liver (20%ID/g), and
spleen (18%ID/g). The blood activity decreased by half in 4 h through renal system.
The tumor uptake was 5%ID/g and remained constant over 24 h.
Chlorotoxin (CTX)-conjugated multifunctional dendrimers labeled with
radionuclide
131 I were synthesized and utilized for targeted SPECT imaging and
radiotherapy of cancer [48]. Amine-terminated PAMAM dendrimers of G5 were
used as a platform. The dendrimers was conjugated with PEG, CTX, and 3-(4′hydroxyphenyl)propionic acid-OSu (HPAO). CTX selectively interacts with matrix
metallopeptidase 2 (MMP-2) which are specifically upregulated in gliomas. The
hydrodynamic size of them were 233.5 nm and the surface potential of the G5.
NHAc-HPAO-(PEG-CTX)-(mPEG) dendrimers was +25.9 mV. The dendrimer
platform was labeled with
131 I using the chloramine-T method through the phenol
group of HPAO moiety. This theranostic dendrimer platform had an ability for
targeted SPECT imaging and radiotherapy of an MMP-2 overexpressing C6 glioma
mouse model.
G4 poly-L-lysine dendrimer was radiolabeled with
188 Re via nitro-imidazole
chelating ligand (ImDendrim) [49]. Nude mice bearing hepatocellular carcinoma
HepG2 xenograft tumors were treated with a 0.1 ml of
188 Re-ImDendrim at doses
of 37, 74, 92.5 and 111 MBq by a single intratumoral injection. After 3 and 24 h
post in situ administration of
188 Re-ImDendrim, SPECT/CT imaging was done. At
24 h post injection of
188 Re-ImDendrim, almost total administered radioactivity
was retained locally in the injection site. There were no significant diffusion outside
the injection area and no significant uptake in various organs including lungs, heart,
liver, kidneys and brain (Fig. 5.5). The cationic poly-L-lysine groups of dendrimer
limit its diffusion rate and showed high retention in the site of injection.
188 Re-ImDendrim treated group showed significant anti-tumor property even with
the lowest dose of 37 MBq per mouse. In comparison, injection of nonradioactive
ImDendrim or free
188 Re did not result in any anti-tumor effect. In situ introduction
of
188 Re-ImDendrim is in phase 1 clinical trial for treatment of inoperable liver
cancers which are non-responding to conventional therapy.
116
K. W. Kang and M. G. Song