Title:Radiopharmaceuticals for the Diagnosis and Therapy of Neuroendocrine Differentiated Prostate Cancer
VOLUME: 10 ISSUE: 1
Author(s):Giampiero Giovacchini, Elisabetta Giovannini, Mattia Riondato and Andrea Ciarmiello
Affiliation:Nuclear Medicine Department, S. Andrea Hospital, Via Vittorio Veneto, 197, 19124 La Spezia
Keywords:Prostate cancer, neuroendocrine differentiation, PET/CT, peptide receptor radionuclide therapy.
Abstract:Neuroendocrine differentiation of prostate cancer (PCa) is a relatively frequent event,
generally understudied, that carries important prognostic information. It is the most frequently observed
during the advanced stages of disease, when PCa has lost its sensitivity to androgen deprivation
therapy or to chemotherapy, moderate to diffuse bone metastatic spread dominates the imaging
scenario and it is responsible for painful clinical symptomatology. However, evidences indicate that
neuroendocrine differentiation is a progressive phenomenon that starts at the very early part of the
pathogenesis of cancer transformation contributing to it. Neuroendocrine tumor phenotypes have reduced
capability to secrete the prostate specific antigen (PSA) and therefore PSA does not represent
a reliable marker to follow-up neuroendocrine differentiation. Tumor progression may be monitored
by measuring plasma concentration of neuroendocrine tumor markers, primarily chromogranin A and
neuron-specific enolase. Several nuclear medicine tracers are available for studying different biochemical
properties of tumor cells with neuroendocrine differentiation. Single photon computed
emission tomography (SPECT) with [111In-diethylenetriaminepentaacetic acid] ([111In-DTPA0])-
octreotide (Octreoscan) has been extensively used in the past. However, the development of the
chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), which in comparison to
DTPA allows higher affinity bindings for beta-emitting radionuclides and for somatostatin (SST)
analogues, and the increased availability of the Germanium-68/Gallium-68 (68Ge/68Ga)-generator,
which enables positron emission tomography/computed tomography (PET/CT) imaging, have allowed
the synthesis of several PET tracers for different SST receptors. The receptor of the bombesin/
gastrin releasing peptide (GRP), which is overexpressed in PCa with neuroendocrine differentiation,
also represents an innovative research field with diagnostic and therapeutic applications
through, respectively, positron and beta emitters. At the moment, however, we observe some discrepancy
between the high number of preclinical studies and the small number of clinical studies,
most likely related to competing and, at the moment, more effective radiopharmaceuticals for imaging
and for radiometabolic therapy, such PET/CT with radiolabeled choline and prostate-specific
membrane antigene (PSMA)-ligands, the latter being labeled either with 68Ga for imaging or with
Lutetium-177 for therapy. Radium-223 dichloride has also been recently successfully introduced for
palliative therapy of bone metastases in PCa. For these reasons, while the development of radiopharmaceuticals
for diagnosis and therapy (theranostics concept) of neuroendocrine differentiated
PCa is scientifically stimulating, the ultimate clinical impact remains presently difficult to predict.
Similar effectiveness in comparison to other forms of diagnostic and radiometabolic radiopharmaceuticals
that have already gained convincing acceptance among referring clinicians needs to be
demonstrated.
