THERANOSTICS: From Molecular Imaging Using Ga-68 Labeled Tracers and PET/CT to Personalized Radionuclide Therapy - The Bad Berka Experience

Abstract

The acronym THERANOSTICS epitomizes the inseparability of diagnosis and therapy, the pillars of medicine and takes into account personalized management of disease for a specific patient. Molecular phenotypes of neoplasms can be determined by molecular imaging with specific probes using positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), or optical methods, so that the treatment is specifically targeted against the tumor and its environment. To meet these demands, we need to define the targets, ligands, coupling and labeling chemistry, the most appropriate radionuclides, biodistribution modifiers, and finally select the right patients for the personalized treatment. THERANOSTICS of neuroendocrine tumors (NETs) using Ga-68 labeled tracers for diagnostics with positron emission tomography/ computed tomography (PET/CT), and using Lu-177 or other metallic radionuclides for radionuclide therapy by applying the same peptide proves that personalized radionuclide therapy today is already a fact and not a fiction.

Keywords: THERANOSTICS; molecular imaging; personalized radionuclide therapy..

Fig 1

Comparison between Ga-68 SSTR PET/CT (PET images upper row and fused PET/CT lower row), and CT (middle row) showing (A) liver metastasis with normal CT, (B) lymph node metastasis with inconclusive CT findings and (C) bone metastasis seen on both PET and CT images.

Fig 2

Whole body “one-stop shop” diagnosis with receptor-PET/CT (A - MIP; B, C and D - PET, CT and fused images) using Ga-68 DOTATOC showing primary neuroendocrine tumor in the ileum (B) with lymph node (C) & bone metastases (D).

Fig 3

Monitoring of molecular response to peptide receptor radionuclide therapy with Lu-177/Y-90 labeled somatostatin analogs by quantification of somatostatin receptor density using Ga-68 somatostatin receptor PET/CT.

Fig 4

The Bad Berka Dose protocol - Analysis of regions of interest around whole body, tumor and normal organs in anterior and posterior planar whole body post-therapy (Lu-177 DOTA-somatostatin analogs) scans at 5 time intervals (A), determination of time activity curves in anterior and posterior scans (B) and using the geometric mean, fitting of the time-activity curves to an exponential function to obtain the residence time of the radiopharmaceutical in the region of interest.

Fig 5

VIPoma patient with Verner Morrison syndrome (severe watery diarrhoea, hypokalemia), high dose octreotide (Sandostatin LAR) prior to PRRNT. After administration of one single cycle of 5 GBq Y-90 DOTATATE, there was no need of octreotide after 3 months, 15 kg weight gain and significant reduction of tumor burden (partial remission. After follow up of 1 year, the liver and kidney functions were normal and only single liver metastasis remained.

Fig 6

Long term effect on renal function depending on the radionuclide used for PRRNT.

Fig 7

Lu-177 BPAMD post-therapy planar images (posterior view) in a patient of metastatic prostate cancer at 5 time intervals for dosimetry, showing high uptake in skeletal metastases with high contrast and long effective half life (retention), and rapid renal clearance.

Fig 8

Example of monitoring therapeutic response by comparison of pre-PRRNT (left) and post-PRRNT Ga-68 somatostatin receptor PET/CT DICOM sets using BBQ-MIT, an automatic, rapid, user-independent routine for segregation and quantification (SUV and tumor volumes) of neoplastic lesions by determine the lesions' borders.