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
M. Sathekge
1   Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
,
J. Wagener
2   Radiochemistry, Necsa, Pretoria, South Africa
,
S. V. Smith
3   ANSTO, Menai, Australia
4   Brookhaven National Laboratory, Upton, NY, USA
,
N. Soni
1   Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
,
B. Marjanovic-Painter
2   Radiochemistry, Necsa, Pretoria, South Africa
,
C. Zinn
1   Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa
,
C. Van de Wiele
5   Department of Nuclear Medicine, University Hospital Ghent, Belgium
,
Y. D’Asseler
5   Department of Nuclear Medicine, University Hospital Ghent, Belgium
,
G. Perkins
3   ANSTO, Menai, Australia
,
J. R. Zeevaart
6   DST/NWU Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa
› Author Affiliations
Further Information

Publication History

received: 13 July 2013

accepted in revised form: 23 September 2013

Publication Date:
12 January 2018 (online)

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).

 
  • References

  • 1 Andrews PA, Howell SB. Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. Cancer Cells 1990; 2: 35-42.
  • 2 Areberg J, Norrgren K, Mattson S. Absorbed doses to patients from 191Pt-, 193mPt- and 195mPt-cisplatin. Appl Radiat Isot 1996; 51: 581-586.
  • 3 Barnham KJ, Djuran MI, Murdoch PS. et al. Ringopened adducts of the anticancer drug carboplatin with sulfur amino acids. Inorg Chem 1996; 35: 1065-1072.
  • 4 Booij J, Sokole EB, Stabin MG. et al. Human biodistribution and dosimetry of (123I)FP-CIT: a potent radioligand for imaging of dopamine transporters. Eur J Nucl Med 1998; 25: 24-30.
  • 5 Chu G. Cellular responses to cisplatin. J Bio Chem 1994; 269: 787-790.
  • 6 De Conti RC, Toftness BR, Lange RC, Creasey WA. Clinical and pharmacological studies with cisdiamminedichloroplatinum. Cancer Res 1973; 33: 1310-1315.
  • 7 De Lange SM, van Groeningen CJ, Kroep JR. et al. Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer. Ann Oncol 2004; 15: 484-488.
  • 8 Eastman A. In: Lippert B. (ed). Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug. Helvetica Chimica Acta; Zurich: Wiley- VCH: Weinheim, Germany 1999: 111-134.
  • 9 Eustace P. History and development of cisplatin in the management of malignant disease. Cancer Nurs 1980; 3: 373-378.
  • 10 Iosilevsky G, Israel O, Frenkel A. et al. A practical SPECT technique for quantitation of drug delivery to human tumors and organ absorbed radiation dose. Semin Nucl Med 1989; 19: 33-46.
  • 11 International Commission on Radiobiological Protection.. Limits for Intakes of Radionuclides by Workers: ICRP Publication 30. New York, NY: Pergamon Press; 1979
  • 12 Jamieson ER, Lippard SJ. Structure, recognition, and processing of cisplatin-DNA adducts. Chem Rev 1999; 99: 2467-2498.
  • 13 Kelland LR. In: Lippert B. (ed). Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug. Helvetica Chimica Acta; Zurich: Wiley- VCH: Weinheim, Germany 1999: 497-521.
  • 14 Kratz F. In: Keppler BK. (ed). Metal Complexes in Cancer Chemotherapy. VCH; Weinheim, Germany: 1993: 391-429.
  • 15 Lagasse LD, Pretorius RG, Petrilli ES. et al. The metabolism of cis-dichlorodiammineplatinum (II): distribution, clearance, and toxicity. Am J Obstet Gynecol 1981; 139: 791-798.
  • 16 Lange R, Spencer R, Harder H. The antitumour agent Cis-Pt(NH3)2Cl2: distribution studies and dose calculations for 193mPt and 195mPt. J Nucl Med 1972; 14: 191-195.
  • 17 Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: An historical perspective and an update. Eur J Cancer 1998; 34: 1522-1534.
  • 18 Osman AM, El-Sayed EM, El-Demersash E. et al. Prevention of cisplatin-induced nephrotoxicity by methimazole. Pharmacol Res 2000; 41: 115-121.
  • 19 Rosenberg B. Fundamental studies of cisplatin. Cancer 1985; 55: 2303-2316.
  • 20 Rosenberg B, Van Camp L, Trosko JE, Mansour VH. Platinum compounds: a new class of potent antitumor agents. Nature 1969; 222: 385-386.
  • 21 Shani J, Bertram J, Russell C. et al. Noninvasive monitoring of drug biodistribution and metabolism: studies with intraarterial 195mPt-cisplatin in humans. Cancer Res 1989; 49: 1877-1881.
  • 22 Smith PHS, Taylor DM. Distribution and retention of the antitumour agent 195mPt-cisdichlorodi - ammineplatinum (II) in man. J Nucl Med 1974; 15: 349-351.
  • 23 Smith SV. inventor; ANSTO, assignee.. Methods of synthesis and use of radiolabelled platinum chemotherapeutic agents. World Intellectual Property Organization patent WO 01/70755 A1. 2001 Sept 27.
  • 24 Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005; 46: 1023-1027.
  • 25 Zicca A, Cafaggi S, Mariggió MA. et al. Reduction of cisplatin hepatoxicity by procainamide hydrochloride in rats. Eur J Pharmacol 2002; 442: 265-272.