THERANOSTIC ROLE OF NUCLEAR MEDICINE
Vikas Prasad
Vice Chair and Senior Physician
Department of Nuclear Medicine
University Hospital of Ulm
Germany
DISCLOSURE OF INTEREST
Ipsen: Consultant
ITM: Consultant
Theranostics is a portmanteau of therapeutics and diagnostics.Theranostics is a proposed diagnostic methodology for personalizing therapeutic intervention/s
Theranostic Concept in Nuclear Medicine
Radiopharmaceuticals-NET
SomatostatinReceptors (SRS)
Serotonin ProductionPathways-C-11 5HTP
Biogenic Amines-
F-18 DOPA
Glucose MetabolismF-18 FDG
Because of the heterogeneity of neuroendocrine tumors in their
functionality, their origin and prognoses,there are overlapping zones amongst the
targets for molecular imaging.
Major Target
Methods for the identification of primary and metastatic
gastroenteropancreatic NETs
Somatostatin-Receptor Imaging
l For imaging somatostatin receptor positive tumor
l SPECT/ PET-Ligand: R-Affinity
l DTPA-Octreotide (ssr2↑, ssr5↑)
l DOTA-Tyr3-Octreotide (DOTA-TOC) (ssr2↑, ssr3↓, ssr5↑↑)
l DOTA-Tyr3-Octreotate (DOTA-TATE) (ssr2↑↑, ssr5↓)
l DOTA-1-Nal3-octreotide (DOTA-NOC) (ssr2↑↑, ssr3↑, ssr5↑)
l DOTA-JR11 (antagonist)
l Radioisotopes
l SPECT Tc-99m, In-111
l PET Ga-68
Ga-68 DOTATOC and Ga-68 DOTATATE approved
Ga-68 SRS PET/CT (3-phase) CUP
a b c
Ileum NET confirmed on
surgery
Detection Rate 50-59%
Prasad V, et al. Eur J Nucl Med Mol Imaging. 2010
Well differentiated, G1/G2 NET,
Proliferation Rate <20%
Pancreatic NET
Insulinoma
MEN-1SSR PET/CT combined with Endosonography
Ga-68 Exendin combined with endosonography
Sporadic
SSR PET/CT combined with Endosonography
Others SSR PET/CT
Ileum
Functional (serotonin producing)
SSR PET/CT
SSR –ve lesions / clinical suspicion –
F-18 DOPA PET/CT
Non functional SSR PET/CT
Rectal
Purely NET SSR PET/CT
Mixed (adeno-neuroendocrine
component)
Role of SSR PET/CT doubtful
CUP, other NET SSR PET/CT
G3 NET, Proliferation Rate
> 20%
If PRRT is under consideration
SMS-R PET/CT
FDG PET/CT
If PRRT is not under
considerationFDG PET/CT
For G3 NEC; CT or MRI are sufficient, in some cases FDG PET/CT for
correct staging might be needed
Peptide Receptor Radionuclide Therapy
14
Aim
Design International, multicenter, randomized, comparator-controlled, parallel-
group
Evaluate the efficacy and safety of 177Lu-Dotatate + SSAs (symptoms
control) compared to Octreotide LAR 60mg (off-label use)1 in patients with
inoperable, somatostatin receptor positive, midgut NET, progressive under
Octreotide LAR 30mg (label use)
Baseline and
Randomization
n = 115
Dose 1
n = 115
Treatment and AssessmentsProgression free survival (RECIST criteria) every 12 weeks
5 Years
follow
up
Dose 2 Dose 3 Dose 4
14
NETTER -1 Study Objectives and Design
1. FDA and EMA recommendation
4 administrations of 7.4 GBq of 177Lu-Dotatate every 8 weeks + SSAs (symptoms control)
Octreotide LAR (high dose - 60mg every 4 weeks1)
Slides Dr. J Strosberg N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
15
N = 229 (ITT)
Number of events: 90
• 177Lu-Dotatate: 23
• Oct 60 mg LAR: 67
15
All progressions centrally confirmed and independently reviewed for eligibility (SAP)
Progression-Free Survival
Octreotide LAR 60 mg
Median PFS: 8.4 months
177Lu-Dotatate
Median PFS: Not reached
Hazard ratio : 0.21 [0.129 –
0.338] p < 0.0001
79% reduction in the risk
of disease
progression/death
Estimated Median PFS in
the Lu-DOTATATE arm
≈ 40 months
Slides Dr. J Strosberg N Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
Median OS 27.4 months in Oct arm
In PRRT arm median OS not reached
Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 4099-4099
DOI: 10.1200/JCO.2018.36.15_suppl.4099
16
Objective Responsescurrently evaluable patients
177-Lu-Dotatate(n=101)*
Sandostatin LAR 60 mg (n=100)*
Complete Response (n) 1 0
Partial Response (n) 17 3
Objective Response Rate (*) 18% 3%
Confidence Interval (95%) 10% - 25% 0% - 6%
Statistical Significance p = 0.0008
All patients (n=116) (n=113)
Progressive Disease 6 (5%) 27 (24%)
Stable Disease 77 (66%) 70 (62%)
(*) Exclude patients with no post-baseline scans or central response available
Slides Dr. J StrosbergN Engl J Med. 2017 Jan 12;376(2):125-135. doi: 10.1056/NEJMoa1607427.
Safety and Tolerability(No. of patients (%), Safety Set; n=221)
17
177-Lu-Dotatate(n=111)
Octreotide LAR 60mg (n=110)
Any adverse event 106 (96%) 95 (86%)
Related to treatment 95 (86%) 34 (31%)
Serious adverse events 29 (26%) 26 (24%)
Related to treatment 10 (9%) 1 (1%)
Withdrawals due to adverse events 7 (6%) 10 (9%)
Related to treatment 5 (5%) 0 (0%)
Slides Dr. J Strosberg
18
Creatinine Clearance
0
20
40
60
80
100
120
Baseline Wk 4 Wk 12 Wk 24 Wk 36 Wk 48 Wk 60 Wk 72 Wk 84 Wk 96
Lutathera
Sando 60 mg
Cre
atin
ine
Cle
aran
ce -
mea
n (
mL
/min
)
177Lu-Dotatate
Octreotide 60 mg
n = 106/96 99/93 100/91 77/61 63/39 52/26 36/14 27/8 14/3 8/3
Slides Dr. J Strosberg
ToxicityBodei, Kidd, Prasad, Modlin
Front Horm Res. 2015;44:198-215
J Clin Oncol 36:2578-2584
J Clin Oncol 36:2578-2584
22
ENETS Guideline-Management of Liver
Metastases from G1-G2 NEN
23
Therapy Options for Advanced Stage NEN
24
Therapy Options Pancreas NEN
COMPETE Study
PRRT with Lu-177 DOTATOC vs
Everolimus
Thank You For Your Attention
