Peptides and Receptors in Image-Guided
Therapy: Theranostics for Neuroendocrine Neoplasms
Richard P. Baum, MD, Harshad R. Kulkarni, MD, and Cecilia Carreras, MD
Theranostics of neuroendocrine neoplasms (NENs) based on molecular imaging using
receptor positron emission tomography/computed tomography (PET/CT) with
68
Ga-labeled
somatostatin (SMS) analogs and molecular radiotherapy applying peptide receptor radio-
nuclide therapy (PRRNT) with
90
Y- and/or
177
Lu-labeled peptides has paved the way to
personalized medicine. SMS receptor PET/CT enables very accurate detection of NENs
and their metastases with high diagnostic sensitivity and specificity and provides quanti-
tative, reproducible data that can be used for selecting patients for PRRNT and evaluation
of therapy response. Among other advantages are the fast imaging protocol (total study
time, 60-90 minutes), low radiation burden (10-12 mSv), flexibility in daily use, and lower
cost than octreotide scintigraphy. As we move toward personalized medicine, the diagnos-
tic information obtained from PET/CT must be improved, that is, by fast routine quantifi-
cation of lesions. PRRNT is highly effective for the treatment of NENs, even in very
advanced cases, and lends a benefit in overall survival of several years. In addition,
significant improvement in clinical symptoms and excellent palliation can be achieved. In
patients with progressive NENs, fractionated, personalized PRRNT with lower doses of
radioactivity given over a longer period (Bad Berka Concept) results in good therapeutic
responses. By this concept, severe hematologic and/or renal toxicity can be reduced or
completely avoided, and the quality of life can be improved. Sequential (DUO-PRRNT) and
concurrent (TANDEM-PRRNT) administrations of radiopeptides are more effective in pro-
gressive NEN than using either radionuclide alone. PRRNT should only be performed at
specialized centers, as NEN patients need highly individualized interdisciplinary treatment
and long-term care.
Semin Nucl Med 42:190-207 © 2012 Elsevier Inc. All rights reserved.
T
heranostics exemplifies the close association between di-
agnosis and therapy for personalized management of dis-
ease. The aim of theranostics in relation to nuclear medicine
is to identify the appropriate molecular targets in neoplasms,
so that the optimal ligands and radionuclides with favorable
labeling chemistry can be selected that enables direct diagno-
sis and treatment specifically toward the individual tumor of
the patient (or toward classes of tumors). Radiolabeled pep-
tides targeting somatostatin (SMS) receptors, which are over-
expressed in the majority of neuroendocrine neoplasms
(NENs), truly represent the essence of theranostics. Molecu-
lar imaging plays a pivotal role in determining the success of
radionuclide therapy. PET/CT using a
68
Ga-labeled SMS an-
alog helps to select patients who are likely to benefit from
peptide receptor radionuclide therapy (PRRNT) using beta
emitters like
177
Lu or
90
Y labeled with the same SMS analog. It
also enables detection of primary and metastatic disease
(staging), assessment of molecular response to therapy, and
long-term follow-up after the initial diagnosis. In addition,
dosimetry is achievable before or after therapy to ensure the
optimum balance between risk and therapeutic benefit and to
predict toxicity. The successful use of
68
Ga for diagnosis, and
of
177
Lu and
90
Y for radionuclide therapy using the same
peptide for targeting SMS receptors (SSTRs), has demon-
strated that theranostics of NENs is already a fact today and
not a fiction.
Theranostics is a term that has been used in the context of
molecular targeting vectors (eg, peptides) labeled either with
diagnostic or with therapeutic radionuclides for the diagnosis
and therapy of a particular disease, targeted specifically by the
vector at its molecular level. Therefore, molecular imaging and
diagnosis of the disease can be effectively followed by personal-
ized treatment using the same molecular imaging vector. One of
Center for Molecular Radiotherapy and Molecular Imaging, ENETS Center
of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany.
Address reprint requests to Richard P. Baum, MD, Center for Molecular
Radiotherapy and Molecular Imaging, Theranostics Research Center,
ENETS Center of Excellence, Zentralklinik Bad Berka, 99437 Bad Berka,
Germany. E-mail: richard.baum@zentralklinik.de
190
0001-2998/12/$-see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1053/j.semnuclmed.2012.01.002