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Molecular Imaging Provides Early Insight Into Neuroendocrine Tumor Outcomes
A proof-of-concept study recently published in The Journal of Nuclear Medicine has demonstrated that molecular imaging can be used to identify early response to 177Lu-DOTATATE treatment in neuroendocrine tumor patients. Utilizing SPECT imaging with 111In-antiγH2AX-TAT, researchers were able to visualize a DNA damage response marker just days after 177Lu-DOTATATE treatment. Monitoring the DNA damage response in the early days after the radionuclide injection could allow physicians to determine the therapeutic outcome and adapt the therapy regimen accordingly.
The radiobiologic aspects of 177Lu-DOTATATE, as well as other molecular radiotherapies, are underexplored. Radionuclide therapy is largely delivered to neuroendocrine tumor patients on a fixed dose protocol, regardless of body weight or tumor uptake. To justify any increase or decrease in the prescribed radionuclide dose, a sustainable metric is needed; however, no metric currently exists.
“One strategy to develop this metric is to determine if sufficient damage has been done to the tumor, which would allow treating physicians to tailor subsequent doses to ensure therapeutic success,” says Bart Cornelissen, PhD, an associate professor in the department of oncology at the MRC Oxford Institute for Radiation Oncology at the University of Oxford in the United Kingdom. “In our study, we sought to image the molecular biological effects of 177Lu-DOTATATE radionuclide therapy by visualizing the DNA double-strand break damage response marker γH2AX.”
In the study, researchers first exposed six cell lines to external beam therapy or 177Lu-DOTATATE and measured the number of γH2AX foci and the clonogenic survival, which indicates the extent of DNA double-strand break damage. Mice bearing the same cell line were then treated with 177Lu-DOTATATE or sham-treated, and static SPECT images were acquired at one, 24, 48, and 72 hours after administration. Immediately after the first SPECT imaging session, the mice were administered 111In-anti-γH2AX-TAT or 111In-IgG-TAT.
In vitro cell lines exposed to 177Lu-DOTATATE were found to have increased γH2AX foci and decreased clonogenic survival, and they reacted very differently than to an equitoxic dose of external beam irradiation. The γH2AX foci induced by 177Lu-DOTATATE in the preclinical models were successfully imaged by SPECT in vivo using 111In-anti-γH2AX-TAT. An accumulation of γH2AX signal was observed over the days after administration of 177Lu-DOTATATE, indicating an increase in DNA damage. Furthermore, γH2AX expression revealed intratumoral and interlesion heterogeneity with the absorbed 177Lu dose, suggesting that different parts of the tumor may react differentially to treatment with 177Lu-DOTATATE.
“The application of this imaging technique could provide a very early indicator of tumor damage without having to wait for changes in tumor volume, which currently may take months,” notes Edward O’Neill, PhD, a postdoctoral researcher in the department of oncology at MRC Oxford Institute for Radiation Oncology. “When using therapeutic response assessment with molecular imaging, making rapid decisions becomes possible, including dose reduction to avoid side effects, assessment of combination therapies, or, in the absence of any measurable response, initiation of palliative options designed toward improving quality of life.”
— Source: SNMMI
Novel Radiotracer Offers Benefits Over Established Prostate Imaging Agent
The novel radiopharmaceutical 18F-PSMA-1007 is effective for detecting malignant prostate cancer lesions and readily available, according to research recently published in The Journal of Nuclear Medicine. With this new agent and 68Ga-PSMA-11, which is already widely used, nuclear medicine departments will now have two options for staging of prostate cancer, potentially increasing availability for patients worldwide.
68Ga-PSMA is a PSMA-labeled tracer commonly used in clinical practice for evaluating the extent of disease in prostate cancer patients. However, 68Ga has a half-life of only 68 minutes (vs 110 min for 18F) and emits a higher-energy positron than 18F.
“The newly introduced 18F-PSMA-1007 has several advantages over the established 68Ga-PSMA,” says Einat Even-Sapir, MD, PhD, director of The Institute for Nuclear Medicine at Tel Aviv Sourasky Medical Center in Israel. “These include a longer half-life, favorable pharmacokinetics, central mass production, and potentially better spatial resolution.”
The prospective study compared the diagnostic accuracy of 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk prostate cancer. 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT were performed within 15 days of each other in 16 patients who were scheduled to undergo a radical prostatectomy. Findings from the two PET tracers were compared with histopathologic findings obtained from radical prostatectomy specimens, considered the gold standard.
Radiolabeled PSMA-avid lesions in the prostate were identified in all 16 patients with almost perfect agreement between the two tracers regarding tumor location. Additionally, in four patients, a second positive focus, though less intense, was detected only by 18F-PSMA-1007. Three of these secondary foci were confirmed as areas of prostate cancer, while the fourth was shown on pathological examination to represent chronic prostatitis.
“In view of the near-equal performance of the two tracers, this preliminary study suggests the routine use of 18F-PSMA-1007 in lieu of 68Ga-PSMA-11 for staging prostate cancer patients; clinicians can use either radiotracer based on availability,” notes Jonathan Kuten, MD, MHA, nuclear medicine specialist at Tel Aviv Sourasky Medical Center. “It also adds to the collective, growing database of evidence supporting the use of PSMA agents for staging intermediate and high-risk patients. We encourage researchers, in the future, to corroborate this study’s results in larger cohorts.”
— Source: SNMMI
