Hybrid scanner reveals risk of plaque rupture

Stanford University researchers have developed a hybrid molecular imaging system that unites optical, radioluminescence and photoacoustic imaging to map the composition of dangerous arterial plaques before they rupture and induce a major cardiac event. The circumferential-intravascular-radioluminescence-photoacoustic-imaging (CIRPI) system aims to detect thin-cap fibro atheroma (TCFA) lesions, which are especially prone to rupture. The scanner provides high-acuity optical imaging via a beta-sensitive probe, as well as radioluminescent marking inside the artery to determine the extent of inflammation. In addition, photoacoustic imaging provides information about the often-complex biological makeup of the plaques (J. Nucl. Med. 58 S1 31).

The researchers performed CIRPI on atherosclerotic samples of human and mouse carotid arteries, following injection of 18F-FDG. They used photoacoustic lasers at different wavelengths to delineate plaque composition. The result was a never-before-seen 360° perspective of arterial plaque burden, confirmed by follow-up radiography, ultrasound and histology. "This is the first clinical imaging system able to detect vulnerable plaque in their earliest stages," said Raiyan Zaman from Stanford University School of Medicine. "Our novel imaging system can detect these vulnerable plaques despite their small size, complex biochemistry and morphology. This could lead to a paradigm shift in the way coronary artery disease is diagnosed and assessed. This is an important and potentially life-saving tool that could one day be used to identify the appropriate treatment plan for patients at risk of future TCFA rupture."

Immuno-PET holds promise for pancreatic tumours

A first-in-human study has demonstrated the feasibility and safety of using a novel antibody-based theranostic agent for diagnosis and therapy of malignancies – such as pancreatic tumours – that express the cancer antigen (CA) 19-9. The researchers, from Memorial Sloan Kettering Cancer Center, evaluated the monoclonal antibody HuMab-5B1 radiolabelled with zirconium-89. Nine patients with CA 19-9-positive metastatic malignancies underwent four whole-body PET/CT scans – on the first day of injection with the imaging agent, then on day two and around days four and seven. Subjects also received a prior diagnostic CT scan to verify the PET/CT results (J. Nucl. Med. 58 S1 385).

The agent was well tolerated and led to no serious side effects. Significant uptake was detected in local tumour recurrences, as well as in metastases, with the highest uptake seen on day seven in the lymph nodes. PET/CT with the antibody led to detection of tiny tumours in the peritoneum and mesenteric lymph nodes that were not found by CT alone. "This new agent is intensely accumulated in pancreatic cancer and finds very small metastases with PET/CT imaging," explained lead author Christian Lohrmann. "There are promising data that HuMab-5B1 could become a theranostic drug used in both targeted imaging and therapy, which could eventually improve the prognosis for pancreatic cancer patients."

Targeted PDT is effective against prostate cancer

A European research team has demonstrated the efficacy of targeted photodynamic therapy (PDT) for treating prostate cancer before and during surgery. The approach targets prostate-specific membrane antigen (PSMA) with an anti-PSMA antibody that's radiolabelled with indium-111 and coupled with photosensitizers that destroy cells upon exposure to near-infrared (NIR) light. A gamma probe is used to detect PSMA-expressing tumour cells. The photosensitizers can then be activated with NIR light, which causes them to fluoresce or emit oxygen radicals that damage tumour tissues. This technique optimizes prostate cancer care by enabling tumour visualization prior to surgery, providing real-time guidance in the operating room, and priming tumours for PDT in cases where surgery isn't suitable (J. Nucl. Med. 58 S1 7).

"Coupling the photosensitizer to an imaging agent that targets PSMA on the tumour surface makes it possible to selectively and effectively destroy prostate tumour remnants and micrometastases while surrounding healthy tissues remain unaffected," said lead author Susanne Lütje from Radboud University Medical Center and University Hospital Essen. The study demonstrated effective localization of the drug at the site of tumours, as well as effective imaging and PDT in mice. The researchers note that further study in humans is needed before this procedure could be used in prostate cancer patients.

Combined therapy slows neuroendocrine tumour growth

Patients with neuroendocrine tumours (NETs) may experience fewer symptoms and survive longer by undergoing peptide-receptor radionuclide therapy (PRRT) combined with a drug that sensitizes tumour cells to radiation therapy, according to a study from the CHU de Québec-Université Laval Research Center. The study evaluated lutetium-177-octreotate (LuTate) PRRT, which can slow the growth of malignant peptide-receptor positive NETs. Damaged cells, however, can naturally repair their DNA, which limits the effectiveness of PRRT. Blocking a protein called PARP can effectively override this process and induce more cell death (J. Nucl. Med. 58 S1 243).

The team studied 3D spheroid models of two human NET cell lines, dosed for five days and then monitored for 15 days. Results showed that more cancer cells died when PRRT and the PARP inhibitor were delivered together than when they were used separately. The combined treatment led to significantly inhibited cell proliferation and increased programmed cell death. "The use of PARP inhibitors is a promising approach to enhance targeted radionuclide therapy for neuroendocrine cancer," said researcher Samuel Adant. "Furthermore, PARP inhibitors could enhance many other current and emerging radionuclide therapies." As both drugs are already approved for use in cancer patients, this method of combining LuTate and PARP inhibitors could be translated readily to the clinic.

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