'Smart Bomb' Delivers Prostate Cancer Drug

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DENVER—Researchers have found a way to combine imaging with chemotherapy in a single agent for the treatment of prostate cancer, according to data presented at the 2009 American Association for Cancer Research 100th Annual Meeting held here.

”It's like a smart bomb, to use a military analogy,” said lead investigator John P. Sedelaar, MD, PhD, a postdoctoral research fellow at The Johns Hopkins University in Baltimore. “By retooling chemotherapy agents, we may be able to get more accurate treatment monitoring and follow-up.” This approach, which has not been used in a clinical setting, offers a novel means to combating prostate cancer.

All the imaging modalities being used in contemporary urological practice—contrast-enhanced transrectal ultrasonography, multimodality 3T MRI, and nuclear bone scans—may be considered prostate imaging modalities and not prostate cancer imaging modalities, Dr. Sedelaar said.

He and his colleagues designed two imaging drugs with a core of thapsigargin, a nonspecific highly cytotoxic agent. These therapeutic agents are modified by adding a tyrosine ring for imaging.

The prodrugs are bound by a specific amino acid sequence, which causes them to be inactive until the sequence is clipped off by either prostate-specific membrane antigen or PSA proteases, according to Dr. Sedelaar. The resulting, activated, free drug is taken up by the prostate cancer cells. This results in a dual “smart bomb” effect, combining targeted prostate cancer-specific imaging and treatment.

“The novelty of the drugs is in the delivery mechanism, as well as the fact that the imaging compound is combined with a therapeutic drug,” Dr. Sedelaar said. “This allows for accurate and image-enhanced detection and delivery. You could say the drugs can search, detect, and destroy because they make use of prostate cancer-specific properties, such as elevated levels of PSA surrounding the prostate cancer cells and increased levels of PSA on the prostate cancer cell membranes.”

Following initial administration of the imaging prodrugs into animal models, researchers noted a measurable reduction in prostate cancer cells. Experiments showed that the imaging prodrugs were cleaved and activated by PSMA or PSA, suggesting their viability as a prostate cancer imaging modality.

“An increasing number of patients have minimal prostate cancer, and they opt for either very focused treatment or the watchful waiting approach,” Dr. Sedelaar said. “In this environment, the need for an accurate imaging tool is paramount.”

He added that this research should be of particular interest to practicing urologists. Clinical trials are scheduled to begin by year's end and will be conducted at two institutions. One concern is that while initial imaging indicated that the prodrug delivering mechanism works, nonspecific uptake by the liver, kidney, spleen, and thyroid was also noted.

“This approach may work well for patients who fail on hormone therapy or chemotherapy and could be offered as a second-line therapy,” said Dr. Sedelaar told Renal & Urology News. “The approach is not novel, but it is novel for prostate cancer treatment.”

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