Molecular imaging + targeted therapy

See the target. Follow the therapy.

An interactive visual story of how molecular targets and native iodine handling connect diagnostic imaging with radiopharmaceutical treatment—from prostate and neuroendocrine tumors to differentiated thyroid cancer.

Explore the pathways
Plain-language captions Responsive layout Evidence-informed education
Overview

Three pathways.
One molecular strategy.

The site follows PSMA, somatostatin receptors, and the thyroid cell's sodium–iodide symporter from biologic target to treatment. Imaging, pathology, laboratory data, and clinical context work together to select patients and assess response.

PSMA pathway

PSMA expression in prostate cancer can be mapped with PSMA PET and targeted with lutetium-177–labeled radioligand therapy in appropriately selected patients.

Somatostatin-receptor pathway

SSTR expression in well-differentiated neuroendocrine tumors can be visualized with DOTATATE PET and targeted using lutetium-177 DOTATATE peptide receptor radionuclide therapy.

Radioiodine pathway

Differentiated thyroid cells can concentrate iodine. In selected patients after thyroidectomy, iodine-131 can ablate remnant tissue or treat iodine-avid residual, recurrent, or metastatic disease.

01 / The cell

A molecular address on the cell surface.

The sculptural cell image introduces PSMA as a target. A later production version could layer in receptor labels, hover states, or a true 3D turntable without changing the visual hierarchy.

Conceptual three-dimensional prostate cancer cell with numerous PSMA receptor proteins across its surface.
Conceptual cell artwork

PSMA expression: Many prostate cancers display increased prostate-specific membrane antigen on the cell surface. Expression varies among and within tumors, so this illustration is explanatory—not a quantitative representation.

02 / Imaging

Molecular signal meets anatomy.

Use the display control to compare PET-emphasized fusion with a grayscale CT-emphasis view, then follow the additional sagittal example to see how PSMA-avid bone disease can appear along the spine.

Axial pelvis • soft-tissue window
Illustrative axial fused PSMA PET/CT of the pelvis with intense tracer uptake at the prostate and posterior bladder wall interface.
Area of interest Intense PSMA-avid uptake is illustrated at the prostate–bladder interface. In clinical practice, interpretation requires the complete study and correlation with anatomic imaging.
Illustrative sagittal fused gallium-68 PSMA PET/CT with several distinct PSMA-avid lesions in cervical, thoracic, and lumbar vertebral bodies, plus expected physiologic activity in the salivary region, liver, kidneys, and urinary bladder.
68Ga-PSMA • Diagnostic PET

A whole-body view can reveal multifocal osseous disease.

In this teaching example, several bright foci localize to vertebral bodies on the sagittal CT, illustrating multiple PSMA-avid osseous metastases. Expected tracer activity in normal organs—especially the salivary glands, kidneys, liver, and urinary bladder—must be distinguished from disease.

Separated foci along the spine illustrate multifocal vertebral involvement.
A complete examination and clinical correlation are required; this synthetic image cannot determine stage or treatment eligibility.
Diagnostic role

68Ga-PSMA maps the target

Gallium-68 is a positron emitter used at diagnostic activity for PET. The scanner detects the resulting 511-keV annihilation photons to show where the PSMA-targeted tracer accumulates. Its purpose here is imaging and patient assessment—not delivery of a tumoricidal radiation dose.

Therapeutic role

177Lu-PSMA delivers treatment

Lutetium-177 emits beta particles that deposit energy over a short tissue range and can damage DNA in targeted and nearby tumor cells. It also emits lower-abundance photons that may be used to image treatment distribution, but its principal role is therapy.

Imaging the therapy

From target map to treatment distribution.

The diagnostic PET/CT identifies PSMA-expressing sites before therapy. After administration, photons emitted by lutetium-177 can be detected with SPECT/CT, allowing the treatment's distribution to be visualized.

Before treatment • Diagnostic68Ga-PSMA PET/CT
Higher resolution
Illustrative pretreatment sagittal gallium-68 PSMA PET/CT showing multiple PSMA-avid cervical, thoracic, and lumbar vertebral body lesions.
Maps PSMA expression before therapy

The sharper PET signal identifies several PSMA-avid vertebral targets and helps establish whether disease distribution is suitable for PSMA-directed treatment.

After treatment • Distribution177Lu-PSMA SPECT/CT
Lower resolution
Illustrative post-treatment sagittal lutetium-177 PSMA SPECT/CT showing radioligand activity at the same cervical, thoracic, and lumbar vertebral body targets.
Shows where the therapeutic radioligand localized

The broader SPECT foci correspond to the pretreatment PET-positive vertebral sites. Beta-minus emissions deliver treatment, while accompanying 113- and 208-keV photons make this post-treatment image possible.

What concordant uptake demonstrates

Activity at the same vertebral targets supports successful radioligand delivery and target engagement. It does not, by itself, prove tumor response or clinical efficacy; those require follow-up imaging, laboratory findings, symptoms, and longitudinal assessment.

03 / Treatment

Targeted delivery, localized effect.

PSMA PET first helps determine whether disease expresses enough target for PSMA-directed therapy. Then, for selected patients, the radioligand binds, internalizes, and delivers short-range beta radiation.

Patient selection

Why PSMA avidity matters.

Lu-177 PSMA therapy depends on the radioligand reaching PSMA-expressing tumor. Greater and more uniform uptake generally signals more available target; absent or markedly heterogeneous uptake can identify disease that may receive less radiation.

Confirm PSMA-positive disease

Current U.S. prescribing information requires selection with an approved PSMA PET product. Eligibility now spans defined metastatic androgen-pathway-modulation-naïve or -sensitive disease treated with Pluvicto plus an ARPI, as well as mCRPC after ARPI therapy before or after taxane in the labeled settings.

Look for heterogeneity—not only the brightest lesion

The pivotal VISION trial required at least one PSMA-positive lesion and excluded patients with certain size-qualified PSMA-negative lesions. A strongly avid focus does not compensate automatically for clinically important non-avid disease elsewhere.

Integrate the complete clinical picture

Uptake intensity alone does not establish eligibility. Disease setting, prior therapy, laboratory values, organ function, marrow reserve, competing imaging findings, and product-specific criteria also matter.

Pluvicto in practice

Three patients—not one “last-line” drug.

For oncologists accustomed to chemotherapy, Pluvicto can be viewed as a PSMA-selected systemic anticancer treatment: it circulates intravenously, treats visible and occult PSMA-expressing disease throughout the body, and has its own response pattern, organ monitoring, dose delays, and cumulative marrow considerations.

Current U.S. status • updated July 31, 2026

Pluvicto is FDA approved for PSMA-positive metastatic castration-resistant prostate cancer after ARPI therapy—either before taxane when delaying chemotherapy is appropriate or after taxane—and, based on PSMAaddition, in combination with an ARPI for PSMA-positive metastatic androgen-pathway-modulation-naïve or -sensitive prostate cancer. The labeled Pluvicto schedule is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until progression or unacceptable toxicity.

Newly metastatic, hormone-sensitive disease: intensify early

A fit patient has de novo metastatic prostate cancer, at least one PSMA-positive metastasis on approved PSMA PET, and is beginning systemic hormonal therapy. The aim is to delay radiographic progression before resistant clones and cumulative morbidity dominate.

Simulated sagittal fused PSMA PET/CT with PSMA-avid pelvic disease and multiple osseous metastases in the spine and pelvis.
Simulated teaching image • sagittal fused PSMA PET/CT
Clinical history
Disease
De novo PSMA-positive metastatic hormone-sensitive prostate cancer with pelvic and osseous disease.
Prior prostate cancer treatment
Prostate biopsy and staging; newly started ADT. No prior ARPI, taxane chemotherapy, or radioligand therapy.
Laboratory readiness
CBC within normal limits. BMP within normal limits.
Use
Continue medical or surgical castration and give Pluvicto with an ARPI. PSMAddition used up to 6 Pluvicto doses every 6 weeks plus ADT and investigator-selected ARPI.
After 2 cycles
Use the two-cycle mark as an early safety-and-response checkpoint—symptoms, CBC, renal function, PSA trend, and imaging when clinically indicated—not as a routinely completed two-dose course.
Why it matters
The PSMAddition trial showed that Pluvicto reduced the risk of progression or death by up to 33% when combined with standard-of-care ARPI and ADT versus standard of care alone.

mCRPC after one ARPI: delay taxane chemotherapy

A patient progresses on abiraterone or enzalutamide, remains taxane-naïve, has PSMA-positive disease, and would benefit from postponing docetaxel because of neuropathy risk, frailty, occupational priorities, or informed preference.

Simulated sagittal fused PSMA PET/CT with multiple PSMA-avid vertebral, pelvic, and nodal metastases.
Simulated teaching image • sagittal fused PSMA PET/CT
Clinical history
Disease
PSMA-positive metastatic castration-resistant prostate cancer with osseous and nodal progression.
Prior prostate cancer treatment
Radical prostatectomy, salvage pelvic radiation, ongoing ADT, and progression after one ARPI. Taxane-naïve.
Laboratory readiness
CBC within normal limits. BMP within normal limits.
Use
Maintain castrate testosterone with ADT and give Pluvicto for up to 6 doses. Do not reflexively sequence to a second ARPI when cross-resistance is likely.
Evidence
In PSMAfore, median rPFS was 9.3 versus 5.6 months for Pluvicto versus ARPI switch (HR 0.41 at the primary analysis); 60% of control patients crossed over, complicating the OS comparison.
Oncology translation
This is not “no treatment while waiting for chemotherapy.” It is active targeted systemic therapy with high PSA and objective response rates and a different toxicity profile from taxanes.

Post-taxane mCRPC: choose against further chemotherapy burden

A patient has PSMA-positive progressive mCRPC after an ARPI and one or two taxane regimens, with painful bone or nodal disease, declining tolerance of cytotoxic therapy, but adequate marrow and renal reserve.

Simulated sagittal fused PSMA PET/CT with high-volume heterogeneous PSMA-avid skeletal metastatic disease.
Simulated teaching image • sagittal fused PSMA PET/CT
Clinical history
Disease
Progressive PSMA-positive metastatic castration-resistant prostate cancer with painful high-volume skeletal disease.
Prior prostate cancer treatment
Definitive local therapy, ongoing ADT, prior ARPI, and docetaxel; later cabazitaxel was stopped because of declining tolerability.
Laboratory readiness
CBC within normal limits. BMP within normal limits.
Use
Maintain ADT and deliver up to 6 cycles with laboratory review before each dose. Coordinate focal external-beam palliative radiation for a painful or structurally threatening lesion when needed.
Evidence
VISION improved median OS (15.3 vs 11.3 months; HR 0.62) and imaging-based PFS (8.7 vs 3.4 months; HR 0.40) when Pluvicto was added to protocol-permitted standard care.
Chemo comparison
TheraP found more PSA50 responses with Lu-PSMA-617 than cabazitaxel (66% vs 37%), fewer grade 3–4 adverse events (33% vs 53%), better patient-reported outcomes, and similar mature OS.

How it fits with familiar treatments

  • ADT: keep the patient effectively castrate throughout treatment; Pluvicto does not replace androgen suppression.
  • ARPI: the Pluvicto-plus-ARPI combination is now FDA approved in PSMA-positive metastatic androgen-pathway-modulation-naïve or -sensitive disease. In mCRPC, continuation or change of ARPI should follow the indication, prior exposure, disease biology, and multidisciplinary plan.
  • Palliative and metastasis-directed radiation: focal external-beam radiation remains useful for pain, impending fracture, cord compression, or another urgent local problem. In the phase 2 LUNAR trial, a different PSMA radioligand product—two cycles of 177Lu-PNT2002—was deliberately combined with SBRT to every visible oligorecurrent site. This supports the broader concept that whole-body PSMA radioligand therapy and focused radiation can be complementary, but the LUNAR sequence is investigational and is not an FDA-approved Pluvicto regimen. Coordinate fields and timing with nuclear medicine and radiation oncology because marrow-rich skeletal irradiation can compound cytopenias.
  • Chemotherapy: Pluvicto may precede taxane in an FDA-defined mCRPC population, compete with cabazitaxel after docetaxel, or be sequenced with docetaxel in investigational strategies. Preserve rather than abandon later options.

“Super responders” and treatment beyond six cycles

“Super responder” is an informal term, not a validated eligibility category. It usually describes an unusually deep and durable biochemical, imaging, and symptomatic response. Favorable signs may include intense, relatively homogeneous PSMA uptake, a large early PSA decline, improving symptoms, preserved counts and renal function, and persistent PSMA expression—but none guarantees duration of benefit.

The FDA-approved initial course remains a maximum of 6 doses. Selected prior responders have received additional cycles or later rechallenge in experienced centers and clinical trials, sometimes using treatment holidays. This can be reasonable to study when disease remains PSMA-avid and marrow, renal, and salivary toxicity are acceptable, but treatment beyond six cycles is not established labeled routine care; prospective trials such as RE-LuPSMA and flexible-schedule studies are testing it.

TrialClinical questionKey findingPractice message
VISION • phase 3Post-ARPI, post-taxane PSMA-positive mCRPC: Pluvicto plus standard care versus standard care.OS 15.3 vs 11.3 months (HR 0.62); imaging-PFS 8.7 vs 3.4 months (HR 0.40).A survival-prolonging systemic option—not merely palliation or a salvage scan-directed procedure.
PSMAfore • phase 3Taxane-naïve mCRPC after one ARPI: Pluvicto versus ARPI switch.Primary median rPFS 9.3 vs 5.6 months (HR 0.41); substantial crossover limited unadjusted OS interpretation.Discuss before chemotherapy when the patient is appropriate to delay taxane; avoid automatic ARPI-to-ARPI sequencing.
PSMAddition • phase 3PSMA-positive metastatic hormone-sensitive disease: Pluvicto plus ADT/ARPI versus ADT/ARPI.Risk of radiographic progression or death reduced by 28% (HR 0.72); OS trend favored combination but was immature.Supports early intensification and the July 31, 2026 U.S. combination approval; the studied and approved course is up to six doses.
TheraP • randomized phase 2Post-docetaxel mCRPC: Lu-PSMA-617 versus cabazitaxel using stringent PSMA/FDG PET selection.PSA50 response 66% vs 37%; grade 3–4 events 33% vs 53%; mature OS similar.A credible alternative to cabazitaxel for appropriately imaged patients, with toxicity and quality-of-life differences that matter.
ENZA-p • randomized phase 2First-line mCRPC: adaptive Lu-PSMA-617 plus enzalutamide versus enzalutamide alone.Median PSA-PFS 13.0 vs 7.8 months (HR 0.43).Supports biologic synergy and adaptive dosing concepts; it does not replace the product label for routine sequencing.
UpFrontPSMA • randomized phase 2De novo high-volume hormone-sensitive disease: two Lu-PSMA-617 cycles followed by docetaxel versus docetaxel alone.Undetectable PSA at 48 weeks: 41% vs 16%, without an observed increase in severe toxicity.The “two-cycle” concept belongs to this investigational sequential chemo strategy—not to the FDA-approved Pluvicto-plus-ARPI regimen.
LUNAR • randomized phase 2Oligorecurrent hormone-sensitive disease with 1–5 PSMA PET-positive lesions: SBRT to all sites versus two neoadjuvant cycles of 177Lu-PNT2002 (6.8 GBq, 6–8 weeks apart) followed by SBRT.Median PFS was 17.6 versus 7.4 months (HR 0.37); median hormone-therapy-free survival was 24.3 versus 14.1 months. Nearly all progression events were new lesions rather than in-field failures.Illustrates a systemic-plus-local strategy aimed at occult micrometastatic disease while ablating visible lesions. LUNAR studied PNT2002—not branded Pluvicto—and does not establish two-cycle Pluvicto plus SBRT as routine care.
Conceptual illustration of a lutetium-177 PSMA radioligand binding to a prostate cancer cell, entering the cell, and emitting beta particles that damage DNA.
Step 1 of 4

Binding to PSMA

The targeting portion of the radioligand recognizes and binds to PSMA proteins on the cancer-cell surface.

Evidence note: This section reflects the July 31, 2026 FDA approval, current U.S. prescribing information, VISION, PSMAfore, PSMAddition, TheraP, ENZA-p, UpFrontPSMA, and the published phase 2 LUNAR trial with its registry record. Trial populations, radioligand products, dosing, and imaging criteria differ. Combination, sequencing, local-radiation timing, and retreatment decisions require multidisciplinary review; verify the current label and institutional protocol before clinical use.
Parallel theranostic pathway: somatostatin-receptor imaging and peptide receptor radionuclide therapy for well-differentiated neuroendocrine tumors. Return to PSMA pathway ↑
04 / Neuroendocrine tumors

Somatostatin receptors connect imaging with therapy.

Many well-differentiated neuroendocrine tumors express somatostatin receptors—especially SSTR2. DOTATATE uses that receptor as a molecular address for diagnostic PET and, in selected receptor-positive GEP-NETs, lutetium-177 peptide receptor radionuclide therapy.

Conceptual three-dimensional well-differentiated neuroendocrine tumor cell with numerous somatostatin receptor subtype 2 proteins and intracellular secretory granules.
Conceptual NET cell artwork

SSTR2 expression: Well-differentiated neuroendocrine tumor cells often retain somatostatin receptors on their surface. Receptor density and distribution vary between patients and lesions, so this illustration explains the target rather than quantifying it.

Diagnostic molecular imagingCoronal 68Ga-DOTATATE PET/CT
PET fusion
Illustrative coronal gallium-68 DOTATATE PET/CT showing multiple somatostatin-receptor-avid liver metastases and a small avid midgut or mesenteric primary focus, with expected physiologic uptake in the pituitary and salivary region, spleen, adrenal glands, kidneys, and urinary bladder.
Reading the scan

Receptor expression becomes visible.

Gallium-68 DOTATATE binds to somatostatin receptors. PET signal therefore reflects receptor distribution—not simply tumor size—and fused CT provides anatomic localization.

Multifocal hepatic diseaseDiscrete avid foci in both hepatic lobes illustrate somatostatin-receptor-positive liver metastases.
Possible midgut or mesenteric primaryA small central abdominal focus illustrates how a compact primary lesion may be conspicuous on receptor-targeted imaging.
Recognize physiologic uptakePituitary, salivary, splenic, adrenal, renal, and urinary activity can be expected. Uptake is not specific for NET and must be interpreted in context.
Diagnostic role

68Ga-DOTATATE maps SSTR expression

Gallium-68 is a positron emitter used for PET localization of somatostatin-receptor-positive NETs. Its diagnostic activity produces a molecular map; it is not administered to deliver a therapeutic tumor dose.

Therapeutic role

177Lu-DOTATATE delivers PRRT

Lutetium-177 DOTATATE binds preferentially to SSTR2, is internalized, and emits beta-minus particles that damage receptor-positive tumor cells and nearby cells. Accompanying photons can also support post-treatment imaging and dosimetry.

Patient selection

Why receptor avidity matters.

PRRT requires sufficient somatostatin-receptor expression for the radiolabeled peptide to localize in tumor. Greater, more uniform uptake generally supports targetability; absent or heterogeneous uptake can indicate disease that may receive less absorbed radiation.

Confirm receptor-positive disease

SSTR PET is used to map receptor expression and disease extent. Tumors without somatostatin receptors may not be visualized and are unlikely to be effectively targeted by DOTATATE.

Compare tumor and background uptake

Clinical protocols commonly assess whether tumor uptake is meaningfully greater than normal background organs such as liver. The complete distribution matters more than one exceptionally avid lesion.

Integrate tumor biology and organ function

Differentiation, grade, disease tempo, prior therapy, renal function, marrow reserve, liver function, symptoms, and receptor heterogeneity all contribute to treatment decisions.

Eligibility + clinical evidence

From receptor uptake to the NETTER trials.

Imaging confirms that the therapeutic target is present, while pathology, disease setting, organ function, prior treatment, and patient goals determine whether lutetium-177 DOTATATE is appropriate.

Proposed imaging criterion

What the Krenning score means

The Krenning score is a visual, semi-quantitative comparison of tumor uptake with normal reference organs. It was developed for indium-111 pentetreotide scintigraphy; a modified version is commonly applied to SSTR PET. Because PET is more sensitive, scores across modalities are not automatically interchangeable.

Practical interpretation: uptake at least equal to liver (score 2 or higher) has often been used as a minimum proposed threshold, while uptake greater than liver (scores 3–4) gives stronger evidence of SSTR targetability. A single score must not override lesion-to-lesion heterogeneity or the full clinical assessment.

0No uptakeNo visible tumor uptake.
1Below liverTumor uptake less than normal liver.
2Equal to liverTumor uptake approximately equal to liver.
3Above liverGreater than liver but below spleen.
4Above spleenTumor uptake greater than spleen.
Completed • phase 3

NETTER-1: PRRT after progression

NETTER-1 randomized 229 adults with inoperable, well-differentiated, SSTR-positive midgut NETs progressing on standard-dose octreotide LAR. Patients received four 7.4-GBq cycles of lutetium-177 DOTATATE plus octreotide LAR 30 mg or high-dose octreotide LAR 60 mg.

Imaging selection: all target lesions had to show uptake at least as high as normal liver on indium-111 pentetreotide imaging—corresponding to Krenning score ≥2.
Main finding: estimated progression-free survival at 20 months was 65.2% with lutetium-177 DOTATATE versus 10.8% with control; the response rate was 18% versus 3%.
Meaning: the trial established major disease-control benefit in progressive midgut NETs. Final overall survival was numerically longer but not statistically significant, with crossover and subsequent therapy complicating interpretation.
Completed primary analysis • phase 3

NETTER-2: PRRT as first-line treatment

NETTER-2 randomized 226 patients with newly diagnosed, advanced, well-differentiated grade 2 or grade 3 GEP-NETs (Ki-67 10%–55%) to lutetium-177 DOTATATE plus octreotide LAR 30 mg or octreotide LAR 60 mg.

Imaging selection: every target lesion required uptake greater than liver—visual uptake score 3 or 4—on an accepted SSTR imaging study.
Main finding: median progression-free survival was 22.8 versus 8.5 months (hazard ratio 0.276), and objective response was 43.0% versus 9.3%.
Meaning: the study supported first-line PRRT for this higher-proliferation, well-differentiated population; it did not compare PRRT directly with chemotherapy, everolimus, or other active systemic options.
Recruiting • phase 3 • NCT06784752

NETTER-3: first-line treatment for lower-grade, high-burden disease

NETTER-3 is evaluating four cycles of lutetium-177 DOTATATE plus octreotide LAR versus octreotide LAR alone in approximately 240 newly diagnosed patients with SSTR-positive, well-differentiated grade 1 or grade 2 GEP-NETs, Ki-67 below 10%, and high disease burden. The listing included participants age 12 years and older as of April 30, 2026.

Key inclusion criteria
  • Metastatic or locally advanced, unresectable, histologically proven G1/G2 GEP-NET diagnosed within 6 months.
  • High disease burden, guided by features such as a lesion >4 cm, multiple lesions >2 cm, alkaline phosphatase >2.5× ULN, bone or peritoneal metastases, tumor-volume symptoms, or hormone-excess symptoms requiring management.
  • All RECIST 1.1 target lesions at least as avid as normal liver on qualifying SSTR imaging within 3 months.
  • At least one measurable lesion; ECOG 0–1; adequate marrow and organ function, including WBC ≥2 × 109/L, platelets ≥75 × 109/L, hemoglobin ≥8 g/dL, creatinine clearance >40 mL/min, and bilirubin ≤3× ULN.
Key exclusion criteria
  • Prior therapeutic radiopharmaceutical for GEP-NET; prior interferon, mTOR inhibitor, chemotherapy, or other systemic therapy apart from limited SSA exposure.
  • More than four prior SSA cycles, inability to hold short-acting octreotide for 24 hours or other SSA for at least 4 weeks before treatment, or prior RECIST progression on SSA.
  • Previous radioembolization, chemoembolization, or radiofrequency ablation; major surgery within 12 weeks.
  • Known brain metastases, relevant hypersensitivity, or severe urinary dysfunction that could prevent adherence to radiation-safety instructions.

Trial criteria are abbreviated for education. The live registry and study team control eligibility, additional protocol-defined criteria may apply, and recruitment status can change.

Side effects + functional tumor support

Why octreotide or lanreotide may continue after Lutathera.

Functional NETs can continue releasing serotonin or other bioactive hormones during and after PRRT. A somatostatin analog suppresses that secretion while the antitumor response to lutetium-177 DOTATATE develops; it is supportive endocrine therapy, not an antidote to radiation toxicity.

Conceptual functional neuroendocrine tumor cell with secretory granules and SSTR2 receptors. A magnified view shows octreotide bound to SSTR2, inhibitory signaling, and reduced granule trafficking and exocytosis. Labeled mediators include serotonin, histamine, tachykinins, bradykinin, prostaglandins, insulin, glucagon, gastrin, and VIP, with associated symptoms including flushing, secretory diarrhea, wheezing, abdominal cramping, hypoglycemia, and peptic symptoms.
Conceptual mechanism: octreotide binding to SSTR2 dampens intracellular signaling and reduces—rather than completely eliminates—release of vasoactive mediators and peptide hormones. The specific substances and symptoms depend on the tumor's site and secretory phenotype.
Maintain hormonal control

Long-acting octreotide or lanreotide may reduce recurrent flushing, secretory diarrhea, wheezing, hypoglycemia, peptic symptoms, or other syndrome-specific effects, depending on which hormones the tumor produces.

Bridge the post-treatment period

PRRT response is not immediate. Continuing the somatostatin analog helps prevent loss of symptom control between cycles and after the four-cycle course. Short-acting octreotide can be used as rescue therapy when clinically indicated.

Coordinate timing with receptor targeting

Long-acting analogs are held before each Lutathera dose because they may compete for somatostatin receptors. The U.S. label specifies octreotide LAR 30 mg 4–24 hours after each Lutathera dose, then every 4 weeks after the course until progression or 18 months from treatment initiation, at physician discretion.

Octreotide versus lanreotide: the U.S. Lutathera prescribing schedule specifically names octreotide LAR. Lanreotide is also used clinically for NET growth and hormone-syndrome control, but its peri-PRRT timing should follow the treating center's protocol. Short-acting octreotide must be withheld for at least 24 hours, and long-acting somatostatin analogs for at least 4 weeks, before each Lutathera dose unless the treating team directs otherwise.

Imaging NET therapy

The diagnostic map and therapeutic distribution align.

Side-by-side imaging illustrates the theranostic link: pretreatment DOTATATE PET maps receptor-positive disease, while post-treatment lutetium-177 SPECT shows where the therapeutic radiopharmaceutical localized.

Before treatment • Diagnostic68Ga-DOTATATE PET/CT
Higher resolution
Illustrative pretreatment coronal gallium-68 DOTATATE PET/CT with multiple receptor-avid liver metastases and a central abdominal primary focus.
Maps receptor-positive disease

Sharper PET foci show the distribution of SSTR-expressing hepatic metastases and the small abdominal target before therapy.

After treatment • Distribution177Lu-DOTATATE SPECT/CT
Lower resolution
Illustrative post-treatment coronal lutetium-177 DOTATATE SPECT/CT showing therapeutic radioligand activity at the same hepatic metastases and central abdominal target.
Confirms therapeutic localization

Broader SPECT foci correspond to the PET-positive targets. Concordance supports delivery and target engagement but does not by itself prove tumor response.

Same receptor, different radionuclide

DOTATATE provides the receptor-binding component in both examples. Gallium-68 supports diagnostic PET; lutetium-177 supplies therapeutic beta-minus emissions and photons suitable for post-treatment imaging.

Conceptual illustration of lutetium-177 DOTATATE binding to SSTR2 on a neuroendocrine tumor cell, internalizing, and emitting beta particles that damage DNA.
Step 1 of 4

Binding to SSTR2

DOTATATE has high affinity for somatostatin receptor subtype 2 on receptor-positive neuroendocrine tumor cells.

NET evidence note: Descriptions are based on the LUTATHERA prescribing information (November 2024), the SNMMI/EANM SSTR PET and PRRT procedure guideline, the phase 3 NETTER-1 publication, the phase 3 NETTER-2 publication, and the NETTER-3 registry record. This educational concept does not replace product labeling, the current study protocol, or multidisciplinary evaluation.
05 / Thyroid cancer

The thyroid's iodine pathway becomes a treatment route.

Differentiated thyroid cells use the sodium–iodide symporter to concentrate iodide. Iodine-131 follows that native pathway, emitting beta particles for treatment and gamma photons that allow post-therapy whole-body imaging.

Patient selection

Not every thyroid cancer needs—or will respond to—radioiodine.

Selection begins with histology, surgical findings, postoperative thyroglobulin and anti-thyroglobulin antibodies, neck ultrasound, stage, recurrence risk, prior radioiodine, and evidence that clinically relevant disease retains iodine avidity. Medullary and anaplastic thyroid cancers do not routinely concentrate iodine and are not treated with I-131.

Remnant ablation

Eliminates residual normal thyroid tissue after total thyroidectomy in selected patients, which may simplify surveillance.

Adjuvant treatment

Targets suspected microscopic disease when recurrence risk and expected benefit justify treatment.

Known disease

Treats iodine-avid residual, recurrent, or metastatic differentiated thyroid cancer when meaningful uptake is expected.

Preparation

Raise TSH and reduce competing iodine

TSH stimulation may use thyroid-hormone withdrawal or recombinant human TSH (Thyrogen), depending on the indication and patient. Medication, supplement, contrast, and dietary iodine exposure are reviewed; the 2025 ATA guideline recommends a low-iodine diet for approximately 1–2 weeks before ablation or treatment.

Pre-treatment checks

Confirm benefit and screen risk

Review pathology, anatomy, laboratory values, renal function, prior administered activity, pregnancy status, breastfeeding, continence, swallowing, home circumstances, and the patient's ability to follow radiation-safety instructions. Diagnostic I-123 or low-activity I-131 imaging and dosimetry are used selectively.

Administration + dosimetry

Activity is indication- and patient-specific

I-131 is usually given orally. Many patients receive protocol-based activity; lesion or blood/marrow dosimetry may support individualized planning in selected metastatic, pediatric, renally impaired, or previously heavily treated patients. Absorbed dose is not interchangeable with administered activity.

Post-therapy imaging

Whole-body imaging maps iodine-avid tissue

Planar whole-body imaging, often with targeted SPECT/CT, is typically performed several days after treatment. It can reveal additional iodine-avid sites and document distribution, but uptake alone does not establish response.

Radiation safety

Protect family, caregivers, and the public

Time, distance, hygiene, toilet precautions, hydration, and sleeping or travel restrictions are individualized to administered activity, measured exposure, living situation, and regulation. Pregnancy is contraindicated. Breastfeeding must stop well before therapy and must not resume for the current child; written site-specific instructions govern release.

Follow-up

Use response-to-therapy assessment

Follow symptoms, examination, TSH-suppressed or stimulated thyroglobulin with antibodies, neck ultrasound, and risk-appropriate anatomic or functional imaging. Rising markers with negative iodine imaging may prompt CT/MRI or FDG PET/CT and evaluation for radioiodine-refractory disease.

Why preparation matters

Make radioactive iodine easier for the cell to capture.

The sodium–iodide symporter (NIS) transports iodide into differentiated thyroid cells. TSH stimulation supports NIS expression and activity, while excess stable “cold” iodine competes with and dilutes I-131, reducing the fraction of radioactive iodine available for uptake.

Conceptual thyroid cell membrane showing iodine-131 entering through the sodium-iodide symporter when competing stable iodine is low, and reduced iodine-131 uptake when excess stable iodine saturates the pathway
Conceptual mechanism. Stable iodine does not permanently plug NIS; a large body iodine pool competes with and dilutes I-131. Reducing avoidable iodine exposure improves the target-to-background opportunity for imaging and therapy.
Thyrogen (rhTSH)

Two prescribed injections raise TSH while the patient remains on thyroid hormone, usually avoiding prolonged hypothyroid symptoms. It is commonly used for remnant ablation and selected adjuvant treatment; its role in distant metastatic disease requires individualized judgment.

Hormone withdrawal

Levothyroxine is stopped according to the treatment protocol so endogenous TSH rises, often targeting a TSH above 30 mIU/L. This may cause fatigue, cognitive slowing, constipation, cold intolerance, or mood symptoms while hypothyroid.

Low-iodine diet

For about 1–2 weeks, avoid major iodine sources such as iodized salt, seaweed, many seafoods, and iodine-containing supplements as directed. Review recent iodinated contrast and amiodarone; do not restrict non-iodized salt unless instructed.

Post-therapy → follow-up

The neck focus disappears after successful remnant ablation.

A post-therapy planar whole-body scan is generally obtained 2–10 days after I-131. Focal uptake in the anterior midline thyroid bed commonly represents residual normal thyroid tissue (a thyroid remnant); depending on pathology and location, uptake can also represent residual iodine-avid disease. I-131 is intended to ablate the remnant and treat iodine-avid cancer.

Simulated anterior and posterior post-therapy iodine-131 whole-body planar scans with focal uptake in the anterior midline lower neck thyroid bed
Post-therapy scan: thyroid-bed uptake.The bright midline neck focus shows I-131 concentrating in remaining iodine-avid tissue after thyroidectomy. This is often benign remnant tissue; correlation with surgery, thyroglobulin, ultrasound, and SPECT/CT determines whether residual tumor is suspected.
Simulated anterior and posterior follow-up iodine whole-body planar scans one year after ablation with no focal uptake in the neck
Illustrative one-year follow-up: no neck uptake.Absence of visible thyroid-bed activity is compatible with successful ablation, but response is not judged from the scan alone; thyroglobulin, anti-thyroglobulin antibodies, neck ultrasound, and clinical risk remain essential.

Simulated teaching images—not patient studies. Physiologic salivary, gastric, bowel, and urinary activity can occur. A negative follow-up scan does not by itself prove that no disease remains.

2025 ATA guidance

Risk guides whether RAI is used and the activity considered.

The newest ATA system has four recurrence-risk tiers: low, low-intermediate, intermediate-high, and high. The table preserves the familiar low/intermediate/high summary while showing the updated intermediate subdivisions.

ATA recurrence riskTypical RAI approachSuggested I-131 activityTherapeutic goal
Low (<10% recurrence)Usually no RAI. If remnant ablation is chosen after shared decision-making, use the lowest effective activity.30–50 mCi (1.1–1.85 GBq)No treatment or remnant ablation
Low-intermediate (10–15%) and intermediate-high (16–30%)Consider RAI; expected benefit varies with adverse histology, nodal burden/location, postoperative thyroglobulin, age, imaging, and patient priorities.30–100 mCi (1.1–3.7 GBq)Remnant ablation ± adjuvant treatment
High (>30%)RAI is typically recommended after total thyroidectomy when disease is expected to be iodine-avid.100–150 mCi (3.7–5.55 GBq)Remnant ablation and adjuvant treatment
Known distant metastasesTreat iodine-avid disease; select empirical activity or individualized dosimetry, especially in advanced age, diffuse pulmonary metastases, renal impairment, or when higher activities are contemplated.100–200 mCi (3.7–7.4 GBq), or dosimetryTreatment of known disease plus remnant ablation

These are guideline ranges, not prescriptions. Final activity depends on treatment intent, pathology, residual disease, iodine avidity, renal and marrow considerations, prior I-131 exposure, dosimetry when appropriate, patient preference, and multidisciplinary review. The 2025 ATA guideline recommends dosimetry when activities above 200 mCi are contemplated.

Thyroid evidence note: Educational content follows the 2025 ATA differentiated thyroid cancer guideline, the SNMMI Procedure Standard/EANM Practice Guideline, and the sodium iodide I-131 prescribing information. Exact preparation, administered activity, inpatient or outpatient release, and follow-up schedules vary by indication, regulation, and institution.
06 / Treatment workflow

One care framework, adapted to three diseases.

Compare how selection, preparation, treatment, dosimetry, safety, and response assessment differ across Lu-177 PSMA, Lu-177 DOTATATE, and I-131. Choose a pathway below.

Interactive comparison

From multidisciplinary decision to longitudinal follow-up

Each pathway requires an authorized treatment team, product- and patient-specific evaluation, clear radiation-safety counseling, and coordinated oncology follow-up.

1Select

Confirm the product-specific prostate-cancer indication and PSMA-positive disease on an approved PET agent; assess non-avid disease, prior therapy, performance status, marrow reserve, and renal function.

2Prepare

Review CBC and renal/hepatic tests, medications, hydration, continence, pain needs, and radiation-safety logistics. Coordinate systemic therapy according to the oncology plan.

3Treat + measure

Administer Lu-177 PSMA intravenously in cycles. Post-treatment imaging can confirm distribution; quantitative SPECT/CT dosimetry is increasingly used but is not identical across centers.

4Protect

Use written distance, hygiene, hydration, toilet, travel, and contact precautions. Monitor for myelosuppression, renal toxicity, dry mouth, nausea, and fatigue.

5Follow

Trend symptoms, performance status, PSA, CBC, renal function, and interval CT/MRI, bone, or PSMA PET imaging when clinically indicated; assess cumulative toxicity before each cycle.

Dosimetry note: Administered activity (MBq or mCi) is the amount given; absorbed dose (Gy) is energy deposited in tissue. Imaging-based dosimetry estimates absorbed dose but methods, timing, calibration, and clinical thresholds vary by therapy and institution.