E-News Exclusives
Targeted Radiopharmaceutical Induces Remission in Pancreatic Cancer Model
A newly developed targeted radiopharmaceutical treatment can effectively slow tumor growth in pancreatic ductal adenocarcinoma (PDAC), according to new research published in the May issue of The Journal of Nuclear Medicine. In preclinical models, the treatment achieved complete remission of the disease, highlighting its potential to transform care for this highly aggressive cancer.
PDAC accounts for over 90% of pancreatic cancer cases and remains one of the most lethal malignancies, with a five-year survival rate of less than 5% in patients with metastatic disease. Although surgery is the only curative approach, it is feasible only in 10% to 20% of patients with localized disease.
"PDAC is very difficult to treat, and new options are urgently needed," says Marika Nestor, a professor in the department of immunology, genetics, and pathology at Uppsala University in Sweden. "Our previous findings suggest a possible new targeted treatment approach for pancreatic cancer patients whose tumors express CD44v6, which may help make treatment more precise and effective."
In the study, researchers evaluated the CD44v6-targeted radiopharmaceutical 177Lu-AKIR001 as a treatment on its own, as well as paired with standard chemotherapy. CD44v6 expression, radioligand binding, and chemotherapy sensitivity were first assessed in four PDAC cell lines. Next, mice bearing PDAC xenografts received 177Lu-AKIR001, chemotherapy, or a combination of the two modalities. Therapeutic efficacy and toxicity for each treatment approach were then determined.
Three of the four PDAC cell lines were found to express CD44v6. In the mouse studies, tumor uptake of 177Lu-AKIR001 was very strong and selective. Tumor growth inhibition was activity-dependent, with complete remissions detected after the administration of 12 megabecquerels (MBq) of 177Lu-AKIR001 (40%) and four MBq of 177Lu-AKIR001 combined with paclitaxel chemotherapy (14%). No significant toxicity was observed.
"Targeted radiotherapies have already transformed treatment for prostate and neuroendocrine tumors," Nestor says. "Our findings suggest that CD44v6 can be added to the list of targets that can be reached with this approach, and, importantly in a cancer where we desperately need new options."
177Lu-AKIR001 radiopharmaceutical therapy is currently being evaluated in patients with other malignancies. The clinical program has recently been expanded to allow broader patient inclusion, and this work can help guide how it could be used in the future, according to Nestor.
— Source: SNMMI
Theranostic Approach Achieves Curative Responses in Colorectal Cancer Tumors
A new pretargeted radioimmunotherapy (PRIT) technique has been shown to be safe and effective in eradicating tumors from a preclinical colorectal cancer model. The multistep theranostic approach delivers alpha-emitting radiation directly to tumors while limiting exposure to healthy tissues. This research was published in the May issue of The Journal of Nuclear Medicine.
Radiopharmaceutical therapy, especially with molecularly targeted alpha-emitting radionuclides, is proving to be transformative in oncology. Among the most promising is the matched 203Pb/212Pb theranostic pair. The toxic effects of 212Pb on the kidneys, however, remain a concern.
"With the toxicity issues that come along with Pb-based radionuclides, PRIT can be especially helpful in making sure the radiation only goes where it is needed," says Sarah M. Cheal, PhD, an assistant professor at Weill Cornell Medicine in New York. "In this study, my colleagues and I developed a novel PRIT approach for colorectal cancer, assessed its biodistribution, and tested various treatment regimens to see what was most effective."
The PRIT approach targeted GPA33, an antigen that is overexpressed in 95% of colorectal tumors. Researchers first performed serial biodistribution and SPECT/CT imaging studies of GPA33-targeted 203Pb/212Pb-DOTA-based PRIT to assess feasibility. Once confirmed, dosimetry was evaluated and various treatment regimens were evaluated in mice bearing human colorectal cancer tumors.
Researchers established that two consecutive doses separated by 48 hours led to prolonged survival—including histologic cures in three out of five mice in the cohort. Mice in this treatment group exhibited normal bone marrow and overall preserved kidney function.
"This PRIT approach produced a combination of effective tumor targeting with minimal toxicity, demonstrating a highly favorable therapeutic window for curative radioimmunotherapy," says Nai-Kong V. Cheung, MD, PhD, Enid A. Haupt Chair in Pediatric Oncology at Memorial Sloan Kettering Cancer Center in New York. "We know there is a significant unmet need for more effective and low-toxicity therapies for advanced colorectal cancer. This study represents an early but important step towards developing a radiopharmaceutical strategy that can meet that need.
"What's more," he says, "because this platform is modular, it can be adapted to many different tumor targets. What is learned for one target could be exploited for others, either for the same tumor or across a wider range of cancers. The 203/212Pb theranostic pairing is especially promising, and our findings support its emerging potential in nuclear medicine and precision oncology."
— Source: SNMMI
