Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers

M. Sathekge; J. Wagener; S. V. Smith; N. Soni; B. Marjanovic-Painter; C. Zinn; C. Van de Wiele; Y. D’Asseler; G. Perkins; J. R. Zeevaart

doi:10.3413/Nukmed-0599-13-06

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2013; 52(06): 222-227
DOI: 10.3413/Nukmed-0599-13-06

Original article

Schattauer GmbH

Biodistribution and dosimetry of ^195mPt-cisplatin in normal volunteers

Imaging agent for single photon emission computed tomographyBiodistribution und Dosimetrie von ^195mPt-Cisplatin bei gesunden ProbandenBildgebendes Radionuklid für die Einzelphotonen- Emissionscomputertomographie

Authors

M. Sathekge

¹Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
J. Wagener

²Radiochemistry, Necsa, Pretoria, South Africa
S. V. Smith

³ANSTO, Menai, Australia

⁴Brookhaven National Laboratory, Upton, NY, USA
N. Soni

¹Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
B. Marjanovic-Painter

²Radiochemistry, Necsa, Pretoria, South Africa
C. Zinn

¹Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
C. Van de Wiele

⁵Department of Nuclear Medicine, University Hospital Ghent, Belgium
Y. D’Asseler

⁵Department of Nuclear Medicine, University Hospital Ghent, Belgium
G. Perkins

³ANSTO, Menai, Australia
J. R. Zeevaart

⁶DST/NWU Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa

Abstract

Summary

^195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. Methods: We investigated the whole-body distribution and radiation dosimetry of ^195mPt-cisplatin in humans. Whole-body scans were obtained up to 144 h after intravenous injection of 112.4 MBq ^195mPt-cisplatin in each of five subjects. Blood samples were taken at various times up to 144 h after injection. Urine was collected up to 114 h after injection for calculation of renal clearance and whole-body clearance. Time/activity curves were generated by fitting the organ-specific geometric mean counts, obtained from regions of interest, on the respective images as a function of the time after injection. OLINDA software package was applied to calculate the absorbed radiation dose for various organs. Results: Most of the activity (32 ± 4%) was excreted in the urine during the first 5 h. The effective clearance half-life derived from extrapolation of the whole-body curve was 40 hours (1.7 days). On average, the highest dose was received by the kidneys (mean dose received 2.68 ± 1.5 mGy/MBq), followed by the spleen (mean dose received 1.6 ± 0.8 mGy/MBq) followed by the liver (mean dose received 1.45 ± 0.38 mGy/MBq). The estimated mean effective dose for the adult subject was 0.185 ± 0.034 mSv/MBq. Conclusion: ^195mPt-cisplatin proved a safe radiopharmaceutical with a favourable bio distribution for early and delayed imaging of pathology above the diaphragm. The ED obtained was 0.185 ± 0.034 mSv/MBq. The highest organ dose was received by the kidneys (2.68 ± 1.5 mGy/ MBq).

Zusammenfassung

^195mPt-Cisplatin ist ein viel versprechendes bildgebendes Radionuklid zur Dosisoptimierung bei einer Chemotherapie mit Cisplatin. Methoden: Wir untersuchten die Ganzkörperverteilung und die Strahlendosimetrie von ^195mPt-Cisplatin in Menschen. Es wurden bis zu 144 h nach intravenöser Injektion von 112,4 MBq ^195mPt-Cisplatin bei allen 5 Probanden Ganzkörperaufnahmen angefertigt. Bis zu 144 h nach der Injektion wurden mehrmals Blutproben abgenommen. Zur Berechnung der renalen Clearance und der Ganzkörper- Clearance wurde über bis zu 144 h Urin gesammelt. Zeit-Aktivitätskurven wurden erzeugt, indem man die organspezifischen geometrischen Mittelwerte aus den interessierenden Bereichen als Funktion der Zeit nach der Injektion auf die entsprechenden Aufnahmen übertrug. Für verschiedene Organe wurde die absorbierte Strahlendosis mittels OLINDA Software-Paket berechnet. Ergebnisse: Der größte Teil der Aktivität (32 ± 4%) wurde im Verlauf der ersten 5 h im Urin ausgeschieden. Die effektive Clearance-Halbwertszeit, extrapoliert aus der Ganzkörperkurve, lag bei 40 Stunden (1,7 Tage). Im Durchschnitt nahmen die Nieren die höchste Dosis auf (mittlere erhaltene Dosis 2,68 ± 1,5 mGy/MBq), gefolgt von der Milz (mittlere erhaltene Dosis 1,6 ± 0,8 mGy/MBq) und der Leber (mittlere erhaltene Dosis 1,45 ± 0,38 mGy/MBq). Die geschätzte mittlere Dosis für einen Erwachsenen betrug 0,185 ± 0,034 mSv/MBq. Schlussfolgerung: ^195mPt-Cisplatin erwies sich als sicheres Radiopharmakon mit vorteilhafter Biodistribution für Früh- und Spätaufnahmen in der bildlichen Darstellung pathologischer Befunde oberhalb des Diaphragmas. Die ED betrug 0,185 ± 0,034 mSv/ MBq. Die höchste Organdosis fanden wir in den Nieren (2,68 ± 1,5 mGy/MBq).

Keywords

^195mPt-cisplatin - normal volunteers - bio-distribution

Schlüsselwörter

^195mPt-Cisplatin - gesunde Probanden - Biodistribution

Full Text

References

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