PMID- 20395330
OWN - NLM
STAT- MEDLINE
DCOM- 20100517
LR  - 20161125
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Linking)
VI  - 51
IP  - 5
DP  - 2010 May
TI  - Time course of Paclitaxel-induced apoptosis in an experimental model of 
      virus-induced breast cancer.
PG  - 775-81
LID - 10.2967/jnumed.109.071621 [doi]
AB  - Early assessment of the efficacy of treatment is important in patients with 
      breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. 
      Irrespective of the exact mechanisms involved in induction, the common early 
      phenotypic marker of apoptosis is the expression on the outer cell membrane 
      surface of phosphatidylserine, which avidly binds annexin V. (99m)Tc-labeled 
      annexin V has been proposed for in vivo scintigraphic detection of apoptosis, 
      albeit with contradicting results. This study was performed to define the time 
      course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model 
      of virus-induced murine breast cancer. METHODS: The RIII virus induces an 
      estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with 
      breast tumors averaging 10 mm were studied, both in baseline conditions and at 
      various times after the intravenous administration of paclitaxel (equivalent to a 
      human dose of 20 mg/70 kg of body weight). The biodistribution of (99m)Tc-annexin 
      V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel 
      administration. Apoptotic and antiapoptotic markers were also evaluated in tumor 
      samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl 
      transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, 
      apoptosis-inducing factor, and Bcl-2 protein. RESULTS: Baseline uptake of 
      (99m)Tc-annexin V in breast tumors was about 2-fold higher than the uptake in 
      normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake 
      increased at 1 and 3 h after paclitaxel administration (to almost double the 
      baseline value) and then declined to levels even lower than baseline. Although no 
      activation of the apoptosis-inducing factor mechanism was detected, a peak in 
      TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to 
      more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a 
      biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline 
      levels at 6 h. CONCLUSION: These results define the time course of various 
      biologic events taking place in this model of murine breast cancer after a 
      proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo 
      uptake of (99m)Tc-annexin V reflects the degree of apoptosis, the study also 
      suggests that the apoptotic response to antitumor therapy may differ from tumor 
      type to tumor type. Therefore, contradicting results previously reported may 
      depend on an inadequate time window chosen for imaging with (99m)Tc-annexin V.
FAU - Erba, Paola A
AU  - Erba PA
AD  - Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, 
      Italy.
FAU - Manfredi, Chiara
AU  - Manfredi C
FAU - Lazzeri, Elena
AU  - Lazzeri E
FAU - Minichilli, Fabrizio
AU  - Minichilli F
FAU - Pauwels, Ernest K J
AU  - Pauwels EK
FAU - Sbrana, Alberto
AU  - Sbrana A
FAU - Strauss, H William
AU  - Strauss HW
FAU - Mariani, Giuliano
AU  - Mariani G
LA  - eng
PT  - Journal Article
DEP - 20100415
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Annexin A5)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Apoptosis Inducing Factor)
RN  - 0 (Organotechnetium Compounds)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (technetium Tc 99m annexin V)
RN  - EC 3.4.22.- (Caspase 3)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Annexin A5/pharmacokinetics
MH  - Antineoplastic Agents, Phytogenic/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Apoptosis Inducing Factor/metabolism
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - Female
MH  - In Situ Nick-End Labeling
MH  - Mammary Neoplasms, Experimental/*diagnostic imaging/*drug therapy/virology
MH  - Mammary Tumor Virus, Mouse
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Organotechnetium Compounds/pharmacokinetics
MH  - Paclitaxel/*therapeutic use
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Radionuclide Imaging
MH  - Radiopharmaceuticals/pharmacokinetics
MH  - Tissue Distribution
EDAT- 2010/04/17 06:00
MHDA- 2010/05/18 06:00
CRDT- 2010/04/17 06:00
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/05/18 06:00 [medline]
AID - jnumed.109.071621 [pii]
AID - 10.2967/jnumed.109.071621 [doi]
PST - ppublish
SO  - J Nucl Med. 2010 May;51(5):775-81. doi: 10.2967/jnumed.109.071621. Epub 2010 Apr 
      15.