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Nucl Med Biol. 2015 May;42(5):465-469. doi: 10.1016/j.nucmedbio.2015.01.007. Epub 2015 Jan 22.

Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

Author information

1
Meander Medical Center, Department of Clinical Pharmacy, Amersfoort, The Netherlands.
2
Meander Medical Center, Department of Radiology & Nuclear Medicine, Amersfoort, The Netherlands.
3
Meander Medical Center, Department of Internal Medicine, Amersfoort, The Netherlands.
4
Section Radiation, Detection & Medical Imaging, TU Delft & MILabs B.V., Utrecht, The Netherlands.
5
Meander Medical Center, Department of Pharmacy, Amersfoort, The Netherlands.
6
Department of Clinical Pharmacology & Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
7
Meander Medical Center, Department of Clinical Pharmacy, Maatweg 3, 3813TZ, Amersfoort, The Netherlands. Electronic address: rob@terheine.nl.

Abstract

INTRODUCTION:

(188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration.

METHODS:

We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice.

RESULTS:

The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP.

CONCLUSIONS:

For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs.

ADVANCES IN KNOWLEDGE:

Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo.

IMPLICATIONS FOR PATIENT CARE:

The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided.

KEYWORDS:

Bone affinity; Hydroxyapatite; Rhenium-188; Rhenium-188-HEDP; Rhenium-HEDP

PMID:
25662844
DOI:
10.1016/j.nucmedbio.2015.01.007
[Indexed for MEDLINE]

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