Studies on incorporated short-lived?-emitters with regard to the induction of late effects

Müller, W.; Schäffer, Eva; Linzner, U.

doi:10.1007/bf01324368

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…Although the amount of free 177 Lu is ≤0.5%, there are reports on its incorporation in the skeleton [5,6,8]. Therefore, preclinical experiments were performed to obtain detailed morphological information.…”

Section: Discussionmentioning

confidence: 99%

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The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

Breeman

Wansem

Bernard

et al. 2003

Eur J Nucl Med Mol Imaging

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Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like (177)Lu. The incorporation of (177)Lu is typically >/=99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free (177)Lu(3+) (= non-DOTA-incorporated) can be substantial. Free (177)Lu(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. (177)Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu(3+) to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (177)LuCl(3), [(177)Lu-DOTA(0),Tyr(3)]octreotate and (177)Lu-DTPA; (b) the possibilities of complexing the free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate to (177)Lu-DTPA prior to intravenous injection; and (c) the effects of free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (177)LuCl(3) had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [(177)Lu-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. (177)Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate could be complexed to (177)Lu-DTPA. Accumulation of (177)Lu in femur, blood, liver and spleen showed a dose relation to the amount of free (177)Lu(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with (177)Lu the addition of DTPA prior to intravenous administration of [(177)Lu-DOTA(0),Tyr(3)]octreotate is strongly recommended.

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Section: Discussionmentioning

confidence: 99%

“…Muller et al reported in a study with mice that 60% of the injected dose (ID) of 177 LuCl 3 is incorporated in the skeleton at 48 h p.i. [5,6]. Li et al reported the stability of 177 Lu-DTPA in vitro in serum [4].…”

Section: Introductionmentioning

confidence: 97%

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

Breeman

Wansem

Bernard

et al. 2003

Eur J Nucl Med Mol Imaging

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“…The clinical efficacy of pain alleviation with β − -emitting radionuclides and radiopharmaceuticals was proven. The benefit of 177 Lu as the therapeutic radionuclide is its accompanying gamma emission, which gives the opportunity for the visualization of the biodistribution of therapeutical agent and eventually monitoring the effect of therapy (Müller, Scháffer, & Linzner, 1980).…”

mentioning

confidence: 99%

Investigation of 177Lu-labeled HEDP, DPD, and IDP as potential bone pain palliation agents

Mirković

Milanović

Stanković

et al. 2020

Journal of Radiation Research and Applied Sciences

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Application of bone-seeking radiopharmaceuticals is one of the modalities in the management of metastatic bone pain. The present study aimed to investigate the potential of 177 Lu-labeled phosphate/phosphonate ligands: 1-hydroxyethane 1,1-diphosphonic acid (HEDP), 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), and imidodiphosphate tetrasodium salt (IDP), as bone pain palliation agents. HEDP, DPD, and IDP were radiolabeled with 177 Lu in high radiolabeling yield (98.49%, 93.31%, and 90.69%, respectively), forming in vitro stable radiolabeled complexes in saline and human serum after 96 h. Biodistribution was followed by imaging studies and ex vivo measurement of radioactivity in organs in healthy Wistar rats. Significant bone accumulation and long retention even after 96 h (3.85 ± 0.91%ID/g), as well as relatively low uptake in soft tissue such as liver and spleen (<1%ID/g), were observed for 177 Lu-HEDP. Two other radiolabeled ligands showed lower accumulations in bone (<1% ID/g) and higher accumulations in liver and spleen at examined time points (>1.5% ID/g). Obtained results suggest that difference in the chemical structure of phosphonates/phosphates influences the rate of bone incorporation of 177 Lu-radiolabeled complexes. Desirable biodistribution pattern of 177 Lu-HEDP makes it suitable for its further preclinical investigations as a potential bone pain palliation agent.

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Pathogenesis of Radionuclide-Induced Bone Tumors

Gössner¹

1985

Metals in Bone

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Studies on incorporated short-lived?-emitters with regard to the induction of late effects

Cited by 7 publications

References 12 publications

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

Investigation of 177Lu-labeled HEDP, DPD, and IDP as potential bone pain palliation agents

Pathogenesis of Radionuclide-Induced Bone Tumors

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