Preclinical evaluation of the orally active camptothecin analog, RFS- 2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer

George P. Amorino, Sherri K. Hercules, Peter J. Mohr, Hongryull Pyo, Hak Choy

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: To test for enhancement of radiation effects in vitro and in vivo by the orally administered camptothecin derivative, 9-nitrocamptothecin (RFS-2000); to study whether the mechanism of this enhancement involves inhibition of sublethal damage recovery. Methods and Materials: In vitro: H460 human lung carcinoma cells were incubated with RFS-2000 for various times at 37°C, irradiated, immediately rinsed, and assessed for colony- forming ability. Sublethal damage recovery (SLDR) was also assessed using two split doses of radiation. In vivo: H460 cell xenografts were used in nude mice. Tumors were grown subcutaneously on the flank, then treated with RFS- 2000 (1 mg/kg) and/or radiation (2 Gy) for 5 consecutive days. Tumor growth delay was then measured for each treatment group. Results: Radiation enhancement was observed in vitro for incubation times between 4 and 24 hr with 10 nM RFS-2000. Using a 24-hr treatment, the radiation dose enhancement ratio values (DER) for 5, 10, and 15 nM were 1.22, 1.54, and 2.0, respectively. Incubation with 10 nM RFS-2000 inhibited SLDR by a factor of 2. The results of three independent in vivo experiments showed that RFS-2000 can enhance the effects of fractionated radiotherapy, with an enhancement factor (EF) of 1.64. Conclusion: Our results show that RFS-2000 can enhance the effects of radiation in human lung cancer cells both in vitro and in vivo, and that the mechanism of this effect may involve the inhibition of SLDR. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)503-509
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume47
Issue number2
DOIs
StatePublished - May 1 2000

Fingerprint

Camptothecin
Radiation
analogs
recovery
augmentation
evaluation
damage
radiation
lungs
tumors
cancer
Radiation Effects
dosage
radiation effects
mice
radiation therapy
Radiation Dosage
rubitecan
Heterografts
Nude Mice

Keywords

  • Camptothecin
  • Lung cancer
  • Radiation
  • Radiotherapy
  • RFS-2000

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Preclinical evaluation of the orally active camptothecin analog, RFS- 2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer. / Amorino, George P.; Hercules, Sherri K.; Mohr, Peter J.; Pyo, Hongryull; Choy, Hak.

In: International Journal of Radiation Oncology Biology Physics, Vol. 47, No. 2, 01.05.2000, p. 503-509.

Research output: Contribution to journalArticle

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