I'm a medical physicist. Two words that sound impressively important and explain absolutely nothing: I track where radioactive drugs go inside the body after they're administered, and I calculate how much radiation every tissue they visit, healthy or not, actually receives. That process is called dosimetry, and it is one of the most important things happening in theranostics right now, and also one of the least understood outside of a handful of academic centers.

This post is my attempt to explain dosimetry in plain terms, make the case for why it matters clinically, and be direct about something that doesn't get enough attention: the patients who stand to benefit most from personalized dosimetry are the same patients who are least likely to have access to it. A lot of those patients live right here in the Appalachian corridor.

Start Here: What Dosimetry Actually Is

When a patient receives a radiopharmaceutical therapy like 177Lu-PSMA-617 (Pluvicto) for prostate cancer or 177Lu-DOTATATE (Lutathera) for neuroendocrine tumors, the treatment works because a radioactive molecule circulates through the body, seeks out its target, and binds to it. The drug goes where the biology takes it, and that includes healthy organs that express the same receptors at low levels, organs responsible for clearing the drug from the body, and tissues that happen to be nearby. Every one of those tissues receives some amount of radiation exposure. The question dosimetry answers is: how much?

That question matters most typically for the kidneys and bone marrow, which are the primary dose-limiting organs for 177Lu-based therapies. The kidneys filter and excrete the drug, which means they are exposed to circulating radioactivity throughout the clearance process. Bone marrow is sensitive to radiation by nature. In both cases, the amount of exposure a patient receives depends heavily on their individual physiology, not on the amount administered. Body composition, organ volume, kidney function, prior treatment history, and tumor burden all affect how the drug distributes and how long it stays in any given tissue.

In practice, dosimetry in nuclear medicine is a quantitative imaging problem. Using the gamma emissions that 177Lu naturally produces, a gamma camera can measure the activity concentration in organs and tumors at multiple time points after therapy. Those measurements are used to construct time-activity curves that describe how the drug accumulates and clears from each tissue. Integrating that curve over time gives the total activity-time product, called the time-integrated activity, for each organ. Multiply that by the appropriate dose factor for the geometry and the isotope, and you get an absorbed dose estimate in Gray. That number tells you whether the kidneys and other organs are within safe limits, whether bone marrow recovery could be at risk, and, separately, how much dose the tumor is receiving. The organ safety information comes first in that workflow, both analytically and clinically.

The Problem with "One Size Fits All"

Current standard of care for most approved theranostic therapies operates on a fixed-activity model. Every patient gets the same amount of drug, every cycle, based on protocols derived from clinical trial populations. For 177Lu-PSMA-617, that means 7.4 GBq per cycle, up to six cycles. ⁵ For 177Lu-DOTATATE, it's 7.4 GBq per cycle, four cycles. ⁶ Full stop.

That approach is not wrong, exactly. It's what the trials were designed around, and the trial results are compelling. The problem is that population-level dosing doesn't account for the individual variation in how patients actually respond. Some patients are getting undertreated because their tumors are concentrating the drug efficiently and could tolerate more. Others are at disproportionate risk of kidney or bone marrow toxicity because of their underlying physiology.

This is not a fringe academic debate. The SNMMI and EANM have published guidance documents ^{1 , 4} supporting dosimetry-based treatment personalization, and the clinical evidence base is building cycle by cycle. The direction of the field is clear: theranostics is moving toward individualized dosing, and dosimetry is how you get there.

Where Post-Therapy SPECT/CT Fits In

Here is where things get concrete. Lutetium-177 is not just a therapeutic isotope. It also emits gamma radiation, which means the same drug that treats the patient can be imaged after it's administered. That's the theranostic principle at work: one molecule, two functions.

Post-therapy SPECT/CT imaging takes advantage of those gamma emissions to produce three-dimensional maps of where the radiopharmaceutical actually went in the patient's body. When those images are acquired at multiple time points after treatment, the rate at which the drug clears from tumors and organs can be calculated. That time-activity data is the input for dosimetry calculations.

Post-therapy imaging is also the foundation for protecting critical organs. Kidney dose is the primary concern for 177Lu-DOTATATE therapy. Data show that patients with preexisting kidney function impairment, or risk factors like diabetes and hypertension, can experience accelerated renal decline at doses that other patients tolerate without issue. ^{1 , 4} Without dosimetry, you don't know where you stand until something goes wrong. With it, you can potentially see it coming and adjust or at the very least you now have additional information to make the best possible decision for your patient.

To be clear about what this looks like in practice: the patient comes in for therapy, receives their treatment, and then returns for one or more post-injection SPECT/CT scans, typically at 24 hours and sometimes at additional time points. At our center we imaging 2-5 hours post-therapy depending on treatment and then again one week later to get a better picture of clearance rates without overburdening the patient. The imaging is non-invasive and uses only the drug already in the patient's system. No additional radioactive material is required. The scan takes roughly 30 to 60 minutes. The resulting data is used to calculate organ and tumor dose, helping inform the clinical team's decisions, and build a patient-specific record of treatment response across cycles.

Why This Is a Specific and Urgent Problem for Appalachia

This is where I want to slow down, because I think this part is underappreciated in most conversations about theranostics access.

The case for dosimetry is generally framed around optimizing outcomes. That framing is correct, but incomplete. Dosimetry is not just about extracting maximum benefit from treatment. It's also about safety, and specifically about protecting patients whose underlying health profile puts them at greater risk of organ toxicity if treatment goes unchecked.

Now consider who lives in Appalachia.

Sources: Appalachian Regional Commission Health Disparities Report ⁷ ; Wang et al., 2025 ⁸

Obesity, diabetes, and hypertension are the major risk factors for reduced kidney function. They are also substantially more prevalent in this region than in the rest of the country. ^{7 , 8} That means an Appalachian patient presenting for theranostic therapy is, on average, more likely to come to the table with a compromised baseline that makes organ toxicity a more immediate concern.

Appalachian patients are also more likely to present with later-stage disease, because access to regular primary care, cancer screening, and early specialty referrals is structurally limited in this region. Later-stage disease means more advanced tumor burden. More advanced tumor burden can change the entire dosimetric picture, including how much of the drug concentrates in tumors versus being absorbed by surrounding healthy tissue.

There is also a logistics dimension to this that matters. Post-therapy dosimetry imaging requires patients to return for scans after treatment. For a patient in a rural county who drove two hours to get to the treatment site, that return trip is not a minor inconvenience. It is a real barrier. That is exactly why programs offering theranostics in community settings need to build dosimetry workflows that account for the practical constraints of the patient population they serve, not just replicate what academic centers do.

The field has begun acknowledging this. Simplified dosimetry approaches, including single-time-point methods and hybrid planar/SPECT protocols, are being developed precisely to reduce the imaging burden on patients and clinics with limited capacity. The science is moving in the right direction. But it only helps patients in communities like ours if providers in those communities know this work exists, understand how to apply it, and have the infrastructure to do it.

What ARC Is Doing About It

One of the core commitments of the Appalachian Radiotheranostics Coalition is that theranostics access in this region should mean real theranostics, not a stripped-down version of it. That means our education and training work includes dosimetry, but distilled down to practical workflows that community-based programs need to be able to execute.

Our workshop curriculum covers post-therapy SPECT/CT protocols, dosimetry calculation frameworks, and organ-at-risk monitoring. Our goal is to help programs across the Knoxville-to-Roanoke corridor understand not just how to administer these therapies, but how to do so in a way that is calibrated to their patients' actual physiology, not just the average patient from a Phase 3 trial enrollment list.

Patients here deserve the same quality of dosimetric oversight that patients at major academic centers receive. Closing that gap is not a technical problem. It is an education and infrastructure problem. That is the problem ARC exists to solve.