Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate.
To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have developed a methodology based on the sodium iodide symporter (NIS). Men with clinically localized prostate cancer were administered an intraprostatic injection of a replication-competent adenovirus, Ad5-yCD/utTK(SR39)rep-hNIS, armed with two suicide genes and the NIS gene. NIS gene expression (GE) was imaged noninvasively by uptake of Na(99 m)TcO(4) in infected cells using single photon emission-computed tomography (SPECT). The investigational therapy was safe with 98% of the adverse events being grade 1 or 2. GE was detected in the prostate in seven of nine (78%) patients at 1 x 10(12) virus particles (vp) but not at 1 x 10(11) vp. Volume and total amount of GE was quantified by SPECT. Following injection of 1 x 10(12) vp in 1 cm(3), GE volume (GEV) increased to a mean of 6.6 cm(3), representing, on average, 18% of the total prostate volume. GEV and intensity peaked 1-2 days after the adenovirus injection and was detectable in the prostate up to 7 days. Whole-body imaging demonstrated intraprostatic gene expression, and there was no evidence of extraprostatic dissemination of the adenovirus by SPECT imaging. The results demonstrate that noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and safe.
Barton
Kenneth N
KN
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA.
Stricker
Hans
H
Brown
Stephen L
SL
Elshaikh
Mohamed
M
Aref
Ibrahim
I
Lu
Mei
M
Pegg
Jan
J
Zhang
Yingshu
Y
Karvelis
Kastytis C
KC
Siddiqui
Farzan
F
Kim
Jae Ho
JH
Freytag
Svend O
SO
Movsas
Benjamin
B
D000256:Adenoviridae / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D005437:Flucytosine / Q000008:administration & dosage; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D000077562:Valganciclovir
D005437:Flucytosine; D000077562:Valganciclovir; D015774:Ganciclovir