DENVER—Magnetic resonance imaging (MRI) is customarily used for prostate imaging. However, by modifying a chemotherapy drug with a radioactive component, scientists should be able to image prostate cancer specifically while simultaneously providing therapy for the disease.
John P. Michael Sedelaar, PhD, MD, a postdoctoral research fellow at Johns Hopkins University, presented these findings at the American Association for Cancer Research 100th Annual Meeting 2009, noting that “By adding a radioactive imaging probe in these compounds, we can combine therapeutics with diagnostic imaging.”
The study, conducted in mice, employed the drug thapsigargin, a nonspecific, highly cytotoxic agent. The researchers added a tyrosine ring to this agent for the coupling of imaging probes. Once in the body, this prodrug is made active by proteins—either prostate-specific membrane antigen (PSMA) or prostate-specific antigen (PSA)—which are more prominently present in prostate cancer, and even more prevalent in highgrade prostate cancer and metastasis.
“This inactivated compound has an amino acid tail specifically chosen so that it can only be ‘clipped' by PSA or PSMA,” Dr Sedelaar explained in an interview with Oncology Nursing News. “When this tail is clipped off, the chemical compound is released and activated and can be taken up into the cell and be therapeutically active.”
“It's like a smart bomb, to use a military analogy,” he continued. “By retooling chemotherapy agents, we may be able to get more accurate treatment monitoring and follow-up.”
Unlike other targeted therapies, this treatment is based upon the general principles of prostate cancer, not the individual patient's genetic makeup. “These smart bombs we're developing are not `tailor-made,'” noted Dr Sedelaar; rather, they are based on “the fact that prostate cancers have elevated amounts of PSA and PSMA.”
The need for targeted approaches to prostate cancer is essential, according to Dr Sedelaar. “An increasing number of patients have minimal prostate cancer, and opt for either very focused treatment or the watchful waiting approach,” he noted. “In this environment, the need for an accurate imaging tool is paramount.”
In terms of the study results, singlephoton emission computed tomography imaging of the tumor-bearing mice showed uptake by tumors together with uptake by thyroid, liver, and spleen. The PSMA imaging drug was also detectable in the kidneys and bladder. No toxicity was noted; and even more importantly, there was a measurable reduction in prostate cancer cells.
When asked whether this approach might be transferable to other cancers and other drugs, Dr Sedelaar would say only that “there could be possibilities to retool the compounds for other chemotherapeutic agents, but we haven't reached that stage yet.”
Dr Sedelaar told Oncology Nursing News that a small multicenter trial of these PSMA therapies will start this year, but in terms of the imaging compounds, “We're still in the animal experiments. The compounds are not yet as specific as we want them to be.” He could provide no details about future human trials.
John P. Michael Sedelaar, PhD, MD, a postdoctoral research fellow at Johns Hopkins University, presented these findings at the American Association for Cancer Research 100th Annual Meeting 2009, noting that “By adding a radioactive imaging probe in these compounds, we can combine therapeutics with diagnostic imaging.”
The study, conducted in mice, employed the drug thapsigargin, a nonspecific, highly cytotoxic agent. The researchers added a tyrosine ring to this agent for the coupling of imaging probes. Once in the body, this prodrug is made active by proteins—either prostate-specific membrane antigen (PSMA) or prostate-specific antigen (PSA)—which are more prominently present in prostate cancer, and even more prevalent in highgrade prostate cancer and metastasis.
“This inactivated compound has an amino acid tail specifically chosen so that it can only be ‘clipped' by PSA or PSMA,” Dr Sedelaar explained in an interview with Oncology Nursing News. “When this tail is clipped off, the chemical compound is released and activated and can be taken up into the cell and be therapeutically active.”
“It's like a smart bomb, to use a military analogy,” he continued. “By retooling chemotherapy agents, we may be able to get more accurate treatment monitoring and follow-up.”
Unlike other targeted therapies, this treatment is based upon the general principles of prostate cancer, not the individual patient's genetic makeup. “These smart bombs we're developing are not `tailor-made,'” noted Dr Sedelaar; rather, they are based on “the fact that prostate cancers have elevated amounts of PSA and PSMA.”
The need for targeted approaches to prostate cancer is essential, according to Dr Sedelaar. “An increasing number of patients have minimal prostate cancer, and opt for either very focused treatment or the watchful waiting approach,” he noted. “In this environment, the need for an accurate imaging tool is paramount.”
In terms of the study results, singlephoton emission computed tomography imaging of the tumor-bearing mice showed uptake by tumors together with uptake by thyroid, liver, and spleen. The PSMA imaging drug was also detectable in the kidneys and bladder. No toxicity was noted; and even more importantly, there was a measurable reduction in prostate cancer cells.
When asked whether this approach might be transferable to other cancers and other drugs, Dr Sedelaar would say only that “there could be possibilities to retool the compounds for other chemotherapeutic agents, but we haven't reached that stage yet.”
Dr Sedelaar told Oncology Nursing News that a small multicenter trial of these PSMA therapies will start this year, but in terms of the imaging compounds, “We're still in the animal experiments. The compounds are not yet as specific as we want them to be.” He could provide no details about future human trials.
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