Los Angeles -- A new type of peptide receptor radionuclide
therapy (PRRT) appears to be safe in metastatic neuroendocrine tumor patients who
have exhausted conventional treatment options. This novel approach, presented
at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting, resulted in partial
remission of the disease in the majority of patients
with advanced cases of neuroendocrine tumors.
Neuroendocrine tumors are a type of cancer that begins from neuroendocrine cells (most commonly
located in the gastrointestinal tract, pancreas, and lungs) and can spread
to other parts of the body. Patients with progressive neuroendocrine tumors
often have limited treatment options, especially after conventional therapies
and approved beta-emitting PRRT have failed. Their prognosis is generally poor,
and there is a clear unmet need for new therapeutic strategies.
"It can be very challenging to treat these patients as they
have already received many different types of therapies," said Elisabetta
Perrone, MD, a nuclear medicine physician at Policlinico Universitario Agostino
Gemelli IRCCS in Rome, Italy. "In our study we explored the safety and efficacy
of a novel PRRT approach that uses a somatostatin receptor (SSTR) antagonist (called
DOTA-LM3) labeled to the alpha-emitting nuclide 225Ac to provide
targeted therapy. Since alpha particles deliver high-energy radiation over a
very short distance: this aspect may help target tumor cells while limiting
unnecessary exposure to close healthy tissues, therefore balancing efficacy and
toxicity an important consideration for patients undergoing systemic therapies."
Twenty patients with different primary origins of well-differentiated
neuroendocrine tumors grade 3 received 225Ac-DOTA-LM3 PRRT
administered as monotherapy (9 cycles) or in TANDEM with the beta-emitting
nuclide 177Lu (32 cycles). After receiving treatment, acute adverse events
and long-term hematologic, renal, and hepatic toxicities were monitored and
graded. Molecular imaging response was evaluated with post-PRRT SPECT/CT and
follow-up 68Ga- DOTA-LM3 PET/CT, and survival was calculated.
The treatment, both as monotherapy and in TANDEM, was
generally well-tolerated, with only mild, self-limiting acute adverse effects,
mainly nausea, and a few cases of long-term toxicities, such as anemia, reduced
white blood cell counts and reduced platelet counts. Molecular imaging
demonstrated complete remission in one patient, partial remission in 10, stable
disease in two patients, and progressive disease in six; one patient
experienced clinical progression to death before post-PRRT imaging. At time of analysis,
11 patients were alive (median follow-up of seven months) and nine had died
(median survival of 18 months).
"This cohort of patients was heterogeneous with respect to
primary tumor site, prior treatments and number of alpha-PRRT cycles;
nevertheless, alpha-PRRT with 225Ac-DOTA-LM3 (as monotherapy or in TANDEM),
showed a manageable acute and long-term safety profile and encouraging
antitumor activity, follow-up and survival outcomes," said Perrone. "Based on
this real-world experience, alpha-PRRT may offer a potential additional option
for selected patients whose tumors still express somatostatin receptors, as
documented by pre-therapeutic 68Ga-DOTA-LM3 PET/CT."
225Ac-DOTA-LM3 PRRT is considered investigational
and is currently offered only in highly specialized centers--including
CURANOSTICUM Wiesbaden-Frankfurt, ICPO Center of Excellence for Advanced Radiomolecular
Precision Oncology in Germany, where this study was conducted under the
guidance of nuclear medicine physician Richard P. Baum, MD, PhD--and generally
within controlled clinical, compassionate use or individualized treatment
settings.
"Before it becomes more broadly available, larger multicenter studies
and prospective clinical trials are needed to confirm efficacy, better define
safety, optimize dosing and identify which patients are most likely to benefit," said Baum.